Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
A Study Combining the Peposertib (M3814) Pill With Standard Chemotherapy in Patients With Ovarian Cancer With an Expansion in High Grade Serous Ovarian Cancer and Low Grade Serous Ovarian Cancer
This phase I trial studies the side effects and best dose of peposertib when given together
with pegylated liposomal doxorubicin hydrochloride in treating patients with high or low
grade ovarian cancer that has come back after a period of improvement (recurrent). Peposertib
may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Drugs used in chemotherapy, such as pegylated liposomal doxorubicin hydrochloride, work in
different ways to stop the growth of tumor cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. Giving peposertib and pegylated
liposomal doxorubicin hydrochloride may work better in treating patients with ovarian cancer
compared to pegylated liposomal doxorubicin hydrochloride alone.
Lisa Barroilhet, MD
Female
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT04092270
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Inclusion Criteria:
• DOSE ESCALATION PHASE: Women with recurrent or persistent epithelial ovarian,
fallopian tube or primary peritoneal cancer are eligible. This includes, but is not
limited to, the following histologic types: serous adenocarcinoma (grade 1,2, or 3/
high grade or low grade), endometrioid adenocarcinoma, carcinosarcoma, mucinous
adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed
epithelial adenocarcinoma, transitional cell carcinoma, or adenocarcinoma not
otherwise specified
• NOTE: Patients who have evidence of DDR deficiency /HRD are eligible if they are
at the point in their disease course where they are appropriate candidates for
single agent Doxil
• EXPANSION PHASE: The expansion phase will simultaneously accrue to 2 cohorts, low
grade serous ovarian cancer (LGSOC) and high grade serous ovarian cancer (HGSOC)
• Patients accrued to the LGSOC cohort will have recurrent or persistent low grade
serous ovarian cancer or grade 1 serous ovarian cancer
• Patients accrued to the HGSOC cohort will have recurrent or persistent high grade
serous ovarian cancer
• Patients must have measurable disease by defined Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1 criteria
• Prior therapy:
• Patients must have received at least one prior line of platinum-based
chemotherapy
• Patients can have received an unlimited number of additional lines of
chemotherapy, targeted therapy, biologic therapy, or hormonal therapy
• Any prior therapy directed at the malignant tumor, including chemotherapy,
biologic/targeted therapy, immunotherapy, or hormonal therapy must be
discontinued at least 4 weeks, one cycle, or 5 half-lives (whichever is shortest)
prior to study treatment initiation
• Age >= 18 years. Because no dosing or adverse event data are currently available on
the use of peposertib (M3814) in combination with pegylated liposomal doxorubicin in
patients < 18 years of age, children are excluded from this study, but will be
eligible for future pediatric trials
• Patients with platinum-sensitive ovarian cancer are eligible for only the dose
expansion phase if their provider feels that PLD would be an appropriate treatment
option for them. Patients with platinum-sensitive ovarian cancer should also be
offered any higher priority studies for which they are potentially eligible and/or
platinum based chemotherapy or a PARP inhibitor if they are eligible for such therapy
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Patients must have a cardiac ejection fraction >= the institutional lower limit of
normal (LLN)
• Hemoglobin >= 9 g/dL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 3 x institutional ULN
• Alkaline phosphatase =< 2.5 x institutional ULN
• Creatinine clearance > 30 ml/min
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
• Patients with treated brain metastases are eligible if follow-up brain imaging after
central nervous system (CNS)-directed therapy shows no evidence of progression. The
patient must be off steroids and clinically stable
• Female patients of childbearing potential must have a negative urine or serum
pregnancy test within 72 hours prior to receiving the first dose of study medication.
If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
test will be required
• The effects of peposertib (M3814) and liposomal doxorubicin on the developing
human fetus are unknown and there is the potential for teratogenic or
abortifacient effects. For this reason, women and men of child-bearing potential
must agree to use adequate contraception (hormonal or barrier method of birth
control; abstinence) prior to study entry, for the duration of study treatment,
and for 6 months after completion of peposertib (M3814) administration. Should a
woman become pregnant or suspect she is pregnant while she or her partner is
participating in this study, she should inform her treating physician
immediately. Because there is an unknown but potential risk for adverse events in
nursing infants secondary to treatment of the mother with peposertib (M3814),
breastfeeding should be discontinued if the mother is treated with peposertib
(M3814)
• Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better
• Ability to understand and the willingness to sign a written informed consent document.
Participants with impaired decision-making capacity (IDMC) who have a
legally-authorized representative (LAR) and/or family member available will also be
eligible
• Archival formalin-fixed paraffin-embedded (FFPE) tissue collected within the past 36
months prior to registration must be available for submission for deoxyribonucleic
acid (DNA)/ribonucleic acid (RNA) analysis
Exclusion Criteria:
• Patients are excluded from the dose-escalation phase of the study if they are eligible
for any available therapies known to confer clinical benefit
• Inability to swallow and/or absorb oral medication (patients with a drainage peg are
ineligible)
• Patients may not have received prior anthracyclines (doxorubicin or pegylated
liposomal doxorubicin) for treatment of their ovarian cancer
• Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual toxicities > grade 1) with the exception of alopecia, thyroid
dysfunction, or neuropathy
• Patients who are receiving any other investigational agents within 28 days prior to
start of treatment
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to peposertib (M3814) or pegylated liposomal doxorubicin
• Patients who cannot discontinue concomitant medications or herbal supplements that
potentially interact with peposertib (M3814)
• The following categories of medications and herbal supplements must be
discontinued prior to starting study treatment:
• Strong inducers/inhibitors of CYP3A4/5, CYP2C9, and CYP2C19
• Substrates of CYP3A4/5, CYP1A2, and CYP2B6 with a narrow therapeutic index
• Use caution with other substrates of CYP3A4/5, CYP1A2, CYP2B6 and substrates of
P-gp, BCRP, OCT1, OATP1B1, and OATP1B3 with a narrow therapeutic index. Close
monitoring is advised
• Because the lists of these agents are constantly changing, it is important to
regularly consult a frequently-updated medical reference. As part of the
enrollment/informed consent procedures, the patient will be counseled on the risk
of interactions with other agents, and what to do if new medications need to be
prescribed or if the patient is considering a new over-the-counter medicine or
herbal product. Patient Drug Interactions Handout and Wallet Card) should be
provided to patients
• Patients who cannot discontinue concomitant proton-pump inhibitors (PPIs). Patients
may confer with the study doctor to determine if such medications can be discontinued.
These must be discontinued >= 5 days prior to study treatment. Patients do not need to
discontinue calcium carbonate
• Patients receiving sorivudine or any chemically related analogues (such as brivudine)
are excluded
• Patients who have received a live attenuated vaccine within 30 days of dosing with
peposertib (M3814)
• Patients with uncontrolled intercurrent illness, including but not limited to ongoing
or active infection
• Patients with psychiatric illness/social situations that would limit compliance with
study requirements
• Pregnant women are excluded from this study because peposertib (M3814) is DNA-PK
inhibitor agent with the potential for teratogenic or abortifacient effects. Because
there is an unknown but potential risk for adverse events in nursing infants secondary
to treatment of the mother with peposertib (M3814), breastfeeding should be
discontinued if the mother is treated with peposertib (M3814). These potential risks
may also apply to other agents used in this study
• Patients with significant (uncontrolled) cardiac conduction abnormalities are excluded
Making Informed Choices on Incorporating Chemoprevention Into Care (MiCHOICE)
This trial studies the implementation of web-based decision support tools for patients with
atypical hyperplasia or lobular carcinoma in situ and healthcare providers. Decision support
tools are designed to improve informed choice about breast cancer chemoprevention.
Recognizing barriers and facilitators that can influence the adoption of decision support
tools at recruitment centers may help researchers learn how to best implement them into
clinical practice.
Kari Wisinski, MD
All
Not specified
N/A
This study is also accepting healthy volunteers
NCT04496739
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Inclusion Criteria:
• Patients must have histologically-confirmed atypical hyperplasia (AH) or lobular
carcinoma in situ (LCIS) documented by breast pathology report at any time in the
past. Patients with borderline breast lesions and pleomorphic LCIS are also eligible
• Patients must be women at least 35 and no more than 74 years of age at registration,
since the Breast Cancer Surveillance Consortium (BCSC) risk calculator is valid only
for this age range
• Both pre/perimenopausal and postmenopausal women are eligible
• Patients must be able to read and write in English or Spanish since study
questionnaires and educational materials are only available in English and Spanish
• Baseline questionnaires must be completed prior to patient registration
• The S1904 Patient Contact form must be completed prior to patient registration
• Patients must be able to access the internet and receive email or text messages. This
is required to access study materials and receive email/text message reminders from
the S1904 Study Team at Columbia University Irving Medical Center (CUIMC). The patient
decision aid, RealRisks, is accessible via smartphones, tablets, or personal
computers. If patients do not own these devices, local study personnel will provide
resources for patients to access RealRisks via computer kiosks or tablets in clinic
waiting rooms or public locations, such as community centers or public libraries
• Patients and healthcare providers must be informed of the investigational nature of
this study and must sign and give written informed consent in accordance with
institutional and federal guidelines
• As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
treating institution's identity is provided in order to ensure that the current
(within 365 days) date of institutional review board approval for this study has been
entered in the system
• IMPLEMENTATION: Providers who enrolled in S1904 at Group 2 (intervention) recruitment
center and consented to future contact are eligible to participate in the interviews
• IMPLEMENTATION EVALUATION: Patients who registered to S1904 at a Group 2
(Intervention) Recruitment Center and consented to be contacted for future research
are eligible to participate in the interviews
• Recruitment Centers must be National Clinical Trials Network (NCTN), National Cancer
Institute Community Oncology Research Program (NCORP) or Minority Underserved
(MU)-NCORP institutions
• Recruitment Centers must have an active EHR and patient portal used in the outpatient
clinics which is common and accessible across all sites belonging to the Recruitment
Center
• Recruitment Centers must be willing to allow the S1904 study team access to the site's
application program interface (API) for integration of the study materials (standard
educational materials and decision support tools) into the EHR and patient portal.
(NOTE: Both Group 1 (control) and Group 2 (intervention) recruitment centers may
access the standard educational materials via the patient portal or uniform resource
locator (URL)/website)
• Recruitment centers must see at least 50 AH and/or LCIS patients per year
• Recruitment centers must identify a lead principal investigator (PI) to facilitate
recruitment and retention of patients and healthcare providers and to participate in
quarterly stakeholder meetings/conference calls
• Recruitment centers must be willing to register at about 16 patients and 5 healthcare
providers to the study
• Recruitment Centers must be willing to submit monthly screening logs to CUIMC
• Providers must regularly see patients with AH or LCIS at an approved recruitment
center
• Providers must be willing to provide informed consent and complete an online baseline
questionnaire
• Providers who will register patients must be registered members of a Cooperative Group
• Providers who register patients to S1904 must be willing to see those same patients
for their 6-month study visits, as the provider intervention tools require that the
"treating investigator" as designated in OPEN and the provider at the 6-month study
visit be the same
Exclusion Criteria:
• Patients must not have a history of invasive breast cancer or ductal carcinoma in situ
• Patients must not have prior or current use of selective estrogen receptor modulators
(SERMs) or aromatase inhibitors (AIs)
• NOTE: The following are approved SERMS and AIs, however, the study is not limited
to these.
• SERMs: tamoxifen, raloxifene
• AIs: anastrozole, exemestane, letrozole
• Patients must not be currently taking hormone replacement therapy
• Patients must not have a history of bilateral mastectomies or breast implants since
the risk calculator is not applicable to these women
• Patients must not be pregnant or lactating
• Premenopausal patients must not have a history of thromboembolism, since it is a
contraindication to tamoxifen. Tamoxifen is the only Food and Drug Administration
(FDA)-approved drug for breast cancer chemoprevention among high-risk premenopausal
women, whereas postmenopausal women are eligible for both SERMs and AIs
Atypical Hyperplasia of the Breast, Lobular Breast Carcinoma In Situ, Pleomorphic Lobular Breast Carcinoma In Situ, Breast
Testing the Use of Combination Therapy in Adult Patients With Newly Diagnosed Multiple Myeloma, the EQUATE Trial
This phase III trial compares the combination of four drugs (daratumumab, bortezomib,
lenalidomide and dexamethasone) to the use of a three drug combination (daratumumab,
lenalidomide and dexamethasone). Bortezomib may stop the growth of cancer cells by blocking
some of the enzymes needed for cell growth. Chemotherapy drugs, such as lenalidomide, work in
different ways to stop the growth of cancer cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. Daratumumab is a monoclonal antibody
that may interfere with the ability of cancer cells to grow and spread. Anti-inflammatory
drugs, such as dexamethasone lower the body's immune response and are used with other drugs
in the treatment of some types of cancer. Adding bortezomib to daratumumab, lenalidomide, and
dexamethasone may be more effective in shrinking the cancer or preventing it from returning,
compared to continuing on daratumumab, lenalidomide, and dexamethasone.
Timothy Schmidt, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04566328
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Inclusion Criteria:
• STEP 0 •Patient must have an Eastern Cooperative Oncology Group (ECOG) performance
status (PS) of 0-2 (PS 3 allowed if secondary to pain)
• STEP 0 •Patient must have newly diagnosed multiple myeloma (MM) by International
Myeloma Working Group (IMWG) criteria
• STEP 0 •Patient must agree to register to the mandatory REVLIMID Risk Evaluation and
Mitigation Strategy (RevREMS) program and be willing and able to comply with the
requirements of RevREMS
• STEP 0 •Patient must be able to undergo diagnostic bone marrow aspirate following
preregistration.
• NOTE: Bone marrow aspirate specimen must be submitted to Adaptive Biotechnologies
for clonoSEQ Assay
• NOTE: Adaptive Biotechnologies will release results to the diagnostic Portal from
the Clonality (ID) test within fourteen (14) days of receipt and reconciliation
of fresh bone marrow specimen to the submitting institution
• STEP 1 •Patient must meet all eligibility criteria in STEP 0 with exception of
allergy requirement
• STEP 1 •Institution must have received the Clonality (ID) test results from Adaptive
Biotechnologies and dominant sequences were identified
• STEP 1 •Patient must have standard risk MM as defined by the Revised International
Staging System (RISS) stage I or II
• NOTE: R-ISS stage is based on serum beta2 microglobulin, albumin and lactate
dehydrogenase (LDH) levels along with presence of chromosomal abnormalities (CA)
detected by interphase fluorescent in situ hybridization (iFISH). Presence of
del(17p), t(4;14), and/or t(14;16) is considered high risk and absence of these,
including any other findings, are standard risk
• R-ISS stage
• Stage I: ISS stage I [beta2 macroglobulin < 3.5 mg/L, albumin > 3.5 g/dL]
AND standard-risk CA AND normal LDH
• Stage II: Not R-ISS stage I or III
• Stage III: ISS stage III [beta2 macroglobulin > 5.5 mg/L] AND high-risk CA
OR high LDH (> upper limit of normal) [patients with stage III are
ineligible]
• STEP 1 •Patient must have measurable or evaluable disease as defined by having one or
more of the following, obtained within 28 days prior to registration:
• >= 1 g/dL monoclonal protein (M-protein) on serum protein electrophoresis
• >= 200 mg/24 hours of monoclonal protein on a 24-hour urine protein
electrophoresis
• Involved free light chain >= 10 mg/dL or >= 100 mg/L AND abnormal serum
immunoglobulin kappa to lambda free light chain ratio (< 0.26 or > 1.65)
• Monoclonal bone marrow plasmacytosis >= 30% (evaluable disease)
• STEP 1 •Patients must have a serum protein electrophoresis (SPEP), urine protein
electrophoresis (UPEP), and serum free light chain (FLC) assay performed within 28
days prior to registration. In addition, a bone marrow biopsy and/or aspirate is
required within 28 days if bone marrow is being followed for response
• NOTE: UPEP (on a 24-hour collection) is required, no substitute method is
acceptable. Urine must be followed monthly if the baseline urine M-spike is >=
200 mg/24 hr. Please note that if both serum and urine M-components are present,
both must be followed in order to evaluate response
• NOTE: The serum free light chain test is required to be done if the patient does
not have measurable disease in the serum or urine. Measurable disease in the
serum is defined as having a serum M-spike >= 1 g/dL. Measurable disease in the
urine is defined as having a urine M-spike >= 200 mg/24 hr
• STEP 1 •Calculated creatinine clearance > 30 mL/min (obtained =< 14 days prior to
Step 1 registration)
• STEP 1 •Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior to
Step 1 registration)
• STEP 1 •Untransfused platelet count >= 75,000/mm^3 (obtained =< 14 days prior to Step
1 registration)
• STEP 1 •Hemoglobin >= 8.0 g/dL (obtained =< 14 days prior to Step 1 registration)
• STEP 1 •Total bilirubin =< 1.5 x ULN (institutional upper limit of normal) (obtained
=< 14 days prior to Step 1 registration)
• STEP 1 •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x
ULN (obtained =< 14 days prior to Step 1 registration)
• STEP 1 •Patient must have received no more than one cycle (28 days or less) of prior
chemotherapy and no more than 160 mg of prior dexamethasone (or equivalent dose of
prednisone) for treatment of symptomatic myeloma. Patient must not have been exposed
to daratumumab for treatment of symptomatic myeloma. Prior radiation therapy to
symptomatic lesions is allowed provided there are no residual toxicity related to
radiation and blood counts meet the study requirements. Radiation treatment must be
completed at least 14 days prior to Step 1 registration
• STEP 1 •Human immunodeficiency virus (HIV)-infected patients on effective
anti-retroviral therapy with undetectable viral load within 6 months of randomization
are eligible for this trial
• STEP 1 •For patients with evidence of chronic hepatitis B virus (HBV) infection, the
HBV viral load must be undetectable on suppressive therapy, if indicated
• STEP 1 •Patients with a history of hepatitis C virus (HCV) infection must have been
treated and cured. For patients with HCV infection who are currently on treatment,
they are eligible if they have an undetectable HCV viral load
• STEP 1 •Patients with a prior or concurrent malignancy whose natural history or
treatment does not have the potential to interfere with the safety or efficacy
assessment of the investigational regimen are eligible for this trial
• STEP 1 •Patients with known history or current symptoms of cardiac disease, or
history of treatment with cardiotoxic agents, should have a clinical risk assessment
of cardiac function using the New York Heart Association Functional Classification. To
be eligible for this trial, patients should be class 2B or better. Patients must not
have evidence of current uncontrolled cardiovascular conditions, including
hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or
myocardial infarction within 6 months prior to Step 1 registration
• STEP 1 •Patient may have a history of current or previous deep vein thrombosis (DVT)
or pulmonary embolism (PE) but must be willing to take some form of anti-coagulation
as prophylaxis if they are not currently on full-dose anticoagulation
• STEP 1 •Patients with a history of chronic obstructive pulmonary disease (COPD) must
have FEV1 testing done within 28 days prior to Step 1 registration and the forced
expiratory volume in 1 second (FEV1) must be > 50% of predicted normal
• STEP 2 •Institution must have received Tracking (MRD) test results from Adaptive
Biotechnologies
• STEP 2 •Patient must have completed the Step 1 Induction phase of this protocol
without experiencing progression
• STEP 2 •Patient must be registered to Step 2 within 8 weeks of completing Step 1
Induction Treatment, counting from last day of completion of last cycle
• STEP 2 •Patient must have an ECOG performance status (PS) of 0-2 (PS 3 allowed if
secondary to pain)
• STEP 2 •Any adverse event(s) related to Step 1 Induction Treatment must have resolved
to grade 2 or less
• STEP 2 •Hemoglobin >= 8 g/dL (obtained within 14 days prior to Step 2 randomization)
• STEP 2 •Platelet count >= 50,000/mm^3 (obtained within 14 days prior to Step 2
randomization)
• STEP 2 •Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained within 14 days prior
to Step 2 randomization)
• STEP 2 •Calculated creatinine clearance >= 30 mL/min (obtained within 14 days prior
to Step 2 randomization)
• STEP 2 •Total bilirubin =< 1.5 x ULN (Institutional upper limit of normal) (obtained
within 14 days prior to Step 2 randomization)
• STEP 2 •ALT and AST < 3 x ULN (obtained within 14 days prior to Step 2 randomization)
Exclusion Criteria:
• STEP 0 •Patient must not have any known allergies, hypersensitivity, or intolerance
to corticosteroids, monoclonal antibodies or human proteins, or their excipients
(refer to respective package inserts or Investigator's Brochure), or known sensitivity
to mammalian-derived products
• STEP 1 •Women must not be pregnant or breast-feeding due to the potential harm and
teratogenic effects to an unborn fetus and possible risk for adverse events in nursing
infants with the treatment regimens being used. All females of childbearing potential
must have a blood test or urine study with a sensitivity of at least 25 mIU/mL within
10-14 days prior to Step 1 registration to rule out pregnancy and again within 24
hours prior to the first dose of lenalidomide. Females of childbearing potential must
also agree to ongoing pregnancy testing while on protocol treatment. A female of
childbearing potential is defined as any woman, regardless of sexual orientation or
whether they have undergone tubal ligation, who meets the following criteria:
• Has achieved menarche at some point,
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal (amenorrhea following cancer therapy does
not rule out childbearing potential) for at least 24 consecutive months (i.e.,
has had menses at any time in the preceding 24 consecutive months)
• STEP 1 •Women of childbearing potential must not expect to conceive children by using
accepted and effective method(s) of contraception (for this protocol defined as the
use of TWO acceptable methods of birth control, one highly effective method and one
additional effective method AT THE SAME TIME for 1) at least 28 days before starting
protocol treatment; 2) while participating in the study; 3) during dose interruptions;
and 4) for at least 3 months days after the last dose of protocol treatment) OR by
practicing true abstinence from sexual intercourse for the duration of their
participation in the study (periodic abstinence [e.g., calendar, ovulation,
symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of
contraception). Men must not expect to father children by practicing true abstinence
from sexual intercourse for the duration of their participation in the study (periodic
abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and
withdrawal are not acceptable methods of contraception) OR use a latex condom during
sexual contact with a female of child bearing potential while participating in the
study and for at least 3 months after the last dose of protocol treatment even if they
have had a successful vasectomy. Men must also agree to abstain from donating sperm
while on study treatment and for 3 months after the last dose of protocol treatment
even if they have had a successful vasectomy. Both women and men must both agree to
abstain from donating blood during study participation and for at least 28 days after
the last dose of protocol treatment
• STEP 1 •Patient must not have peripheral neuropathy >= grade 2 on clinical
examination or grade 1 with pain at time of Step 1 registration
• STEP 1 •Patient must not have any serious medical or psychiatric illness that could,
in the investigator's opinion, potentially interfere with the completion of treatment
according to this protocol
• STEP 1 •Patient must not have moderate or severe persistent asthma within the past 2
years, or uncontrolled asthma of any classification
• NOTE: Patients who currently have controlled intermittent asthma or controlled
mild persistent asthma are allowed to register
• STEP 1 •Patient must not receive any other concurrent chemotherapy, or any ancillary
therapy considered investigational while on this protocol
• NOTE: Bisphosphonates are considered to be supportive care rather than therapy,
and are thus allowed while on protocol treatment
• STEP 2 •Patient must not have received any non-protocol therapy outside of the
assigned Step 1 Induction treatment including stem cell transplant
• STEP 2 •Women must not be pregnant or breast-feeding due to the potential harm and
teratogenic effects to an unborn fetus and possible risk for adverse events in nursing
infants with the treatment regimens being used. All females of childbearing potential
must have a blood test or urine study with a sensitivity of at least 25 mIU/mL within
10-14 days prior to Step 2 randomization to rule out pregnancy and again within 24
hours prior to the first dose of lenalidomide. Females of childbearing potential must
also agree to ongoing pregnancy testing while on protocol treatment. A female of
childbearing potential is defined as any woman, regardless of sexual orientation or
whether they have undergone tubal ligation, who meets the following criteria:
• Has achieved menarche at some point,
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal (amenorrhea following cancer therapy does
not rule out childbearing potential) for at least 24 consecutive months (i.e.,
has had menses at any time in the preceding 24 consecutive months).
• STEP 2 •Women of childbearing potential must not expect to conceive children by using
accepted and effective method(s) of contraception (for this protocol defined as the
use of TWO acceptable methods of birth control, one highly effective method and one
additional effective method AT THE SAME TIME for 1) at least 28 days before starting
protocol treatment; 2) while participating in the study; 3) during dose interruptions;
and 4) for at least 3 months days after the last dose of protocol treatment) OR by
practicing true abstinence from sexual intercourse for the duration of their
participation in the study (periodic abstinence [e.g., calendar, ovulation,
symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of
contraception).
Men must not expect to father children by practicing true abstinence from sexual
intercourse for the duration of their participation in the study (periodic abstinence
[e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not
acceptable methods of contraception) OR use a latex condom during sexual contact with a
female of child bearing potential while participating in the study and for at least 3
months after the last dose of protocol treatment even if they have had a successful
vasectomy. Men must also agree to abstain from donating sperm while on study treatment and
for 3 months after the last dose of protocol treatment even if they have had a successful
vasectomy. Both women and men must both agree to abstain from donating blood during study
participation and for at least 28 days after the last dose of protocol treatment
Plasma Cell Myeloma, RISS Stage I Plasma Cell Myeloma, RISS Stage II Plasma Cell Myeloma, Multiple Myeloma
A Study of Combination Chemotherapy for Patients With Newly Diagnosed DAWT and Relapsed FHWT
This phase II trial studies how well combination chemotherapy works in treating patients with
newly diagnosed stage II-IV diffuse anaplastic Wilms tumors (DAWT) or favorable histology
Wilms tumors (FHWT) that have come back (relapsed). Drugs used in chemotherapy regimens such
as UH-3 (vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan)
and ICE/Cyclo/Topo (ifosfamide, carboplatin, etoposide, cyclophosphamide, and topotecan) work
in different ways to stop the growth of tumor cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. This trial may help doctors find out
what effects, good and/or bad, regimen UH-3 has on patients with newly diagnosed DAWT and
standard risk relapsed FHWT (those treated with only 2 drugs for the initial WT) and regimen
ICE/Cyclo/Topo has on patients with high and very high risk relapsed FHWT (those treated with
3 or more drugs for the initial WT).
Kenneth Desantes, M.D.
All
up to 30 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT04322318
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Inclusion Criteria:
• Patients with newly diagnosed stages 2 •4 diffuse anaplastic Wilms tumor must be
enrolled on AREN03B2 and have received an initial risk assignment showing DAWT (if
anaplasia first identified at diagnostic, pre-treatment nephrectomy or biopsy) or a
delayed nephrectomy classification showing DAWT (if anaplasia first noted at delayed
nephrectomy) prior to enrollment on AREN1921. Prior enrollment on AREN03B2 is not an
eligibility requirement for patients with relapsed favorable histology Wilms tumor.
• Patients must be =< 30 years old at study enrollment
• Patients with the following diagnoses are eligible for this study:
• Newly diagnosed stages 2 •4 diffuse anaplastic Wilms tumor as confirmed by
central review
• Favorable histology Wilms tumor at first relapse. Relapsed FHWT patients must
have previously achieved remission for their initial FHWT diagnosis to be
eligible for this study. The relapse risk groups are defined as follows,
regardless of radiation therapy:
• Standard-Risk relapse: Patients who received two chemotherapy agents for
frontline therapy; primarily actinomycin D and vincristine
• High-Risk relapse: Patients who received three chemotherapy agents for
frontline therapy; primarily vincristine, actinomycin D and doxorubicin or
vincristine, actinomycin D and irinotecan
• Very High-Risk relapse: Patients who received four or more chemotherapy
agents as part of initial therapy; primarily regimen M or its variations
• Patients with newly diagnosed DAWT must have had histologic verification of the
malignancy. For relapsed FHWT patients, biopsy to prove recurrence is encouraged, but
not required
• Note: For relapsed FHWT patients, an institutional pathology report confirming
favorable histology Wilms tumor (from relapse, if available, or from original
diagnosis) must be available for upload prior to initiation of protocol therapy
• Patients with newly diagnosed Stages 2 •4 diffuse anaplastic Wilms tumor must be
enrolled on AREN1921 within 2 weeks of the tumor-directed surgery or biopsy procedure
that first confirms a diagnosis of DAWT, whether at initial diagnostic procedure or
delayed nephrectomy (such surgery/biopsy is day 0). For patients who received prior
therapy for presumed favorable histology Wilms tumor, later confirmed to have diffuse
anaplastic Wilms tumor at subsequent review of the initial biopsy
• Patients with newly diagnosed DAWT who undergo upfront nephrectomy must have at least
1 lymph node sampled prior to study enrollment
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age
• Patients must have a life expectancy of >= 8 weeks
• Diffuse Anaplastic Wilms Tumor: Patients with diffuse anaplastic histology must have
had no prior systemic therapy, except in the following situations:
• Patients with diffuse anaplastic Wilms tumor who received no more than 12 weeks
of pre nephrectomy chemotherapy for what was originally presumed to be favorable
histology Wilms tumor, subsequently confirmed to be diffuse anaplastic Wilms
tumor at delayed nephrectomy
• Patients with diffuse anaplastic Wilms tumor who received no more than 6 weeks of
chemotherapy following upfront biopsy, initiated within 14 days of biopsy, for
presumed favorable histology Wilms tumor based on institutional review, but
subsequently corrected to diffuse anaplastic Wilms tumor based on the AREN03B2
initial risk assignment results (if available per current version of AREN03B2)
• Treatment consisting of vincristine/doxorubicin/cyclophosphamide initiated on an
emergent basis and within allowed timing as described
• Note: Patients who received prior therapy for presumed favorable histology Wilms
tumor, later identified to have diffuse anaplastic Wilms tumor as per above, must
begin study treatment starting at cycle 3 (week 7) of regimen UH 3. Patients who
received emergency radiation to preserve organ function are eligible as noted.
Patients who received radiation as part of standard of care for presumed newly
diagnosed favorable histology Wilms tumor, along with chemotherapy as noted
above, prior to identification of diffuse anaplasia, are also eligible
• Relapsed Favorable Histology Wilms Tumor: Patients must not have received prior
chemotherapy for their relapsed favorable histology Wilms tumor diagnosis. In
addition, patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry
onto this study
• Radiation therapy (RT): >= 2 weeks (wks) must have elapsed for local palliative
RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >=
50% radiation of pelvis; >= 6 wks must have elapsed if other substantial bone
marrow (BM) radiation. Patients with relapsed favorable histology Wilms tumor who
received emergency radiation to preserve organ function are eligible and do not
need to washout with the above criteria
• Patients may not be receiving any other investigational agents (within 4 weeks prior
to study enrollment)
• Peripheral absolute neutrophil count (ANC) >= 750/uL (performed within 7 days prior to
enrollment)
• Platelet count >= 75,000/uL (transfusion independent) (performed within 7 days prior
to enrollment)
• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (performed
within 7 days prior to enrollment)
• Patients with high-risk or very high-risk relapsed FHWT who will be treated with
regimen ICE/Cyclo/Topo, must have renal function assessed by creatinine clearance or
radioisotope glomerular filtration rate (GFR) and meet the following requirement:
• Creatinine clearance or radioisotope GFR >= 60 mL/min/1.73 m^2 (performed within
7 days prior to enrollment)
• Patients diagnosed with stage 2-4 DAWT or standard risk relapsed FHWT, who will be
treated with regimen UH 3, may either obtain a creatinine clearance, radioisotope GFR
(meeting the above criteria of GFR >= 60 mL/min/1.73 m^2), or an adequate serum
creatinine as per the following table:
• Age: Maximum Serum Creatinine (mg/dL)
• 1 month to < 6 months: 0.4 (male and female)
• 6 months to < 1 year: 0.5 (male and female)
• 1 to < 2 years: 0.6 (male and female)
• 2 to < 6 years: 0.8 (male and female)
• 6 to < 10 years: 1 (male and female)
• 10 to < 13 years: 1.2 (male and female)
• 13 to < 16 years: 1.5 (male), 1.4 (female)
• >= 16 years: 1.7 (male), 1.4 (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age or direct bilirubin =<
ULN for patients whose total bilirubin > 1.5 x ULN (performed within 7 days prior to
enrollment)
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x
upper limit of normal (ULN) for age or =< 5 x ULN for patients with liver metastases
(performed within 7 days prior to enrollment)
• Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by
radionuclide angiogram (obtained within 21 days prior to enrollment and start of
protocol therapy)
Exclusion Criteria:
• Patients with a history of bilateral Wilms tumor (synchronous or metachronous)
• Patients with any uncontrolled, intercurrent illness including, but not limited to,
ongoing or active infection, or symptomatic congestive heart failure (defined as grade
2 or higher heart failure per Common Terminology Criteria for Adverse Events [CTCAE]
version 5.0)
• Relapsed FHWT patients who did not receive frontline chemotherapy (e.g., very low risk
FHWT initially observed without chemotherapy) or received only one chemotherapy agent
for frontline therapy
• For patients with high-risk or very high-risk relapsed FHWT:
• Patients with renal tubular acidosis (RTA) as evidenced by serum bicarbonate < 16
mmol/L and serum phosphate =< 2 mg/dL (or < 0.8 mmol/L) without supplementation
• For stages 2-4 DAWT and standard-risk relapsed FHWT patients:
• Chronic inflammatory bowel disease and/or bowel obstruction
• Concomitant use of St. John's wort, which cannot be stopped prior to the start of
trial treatment
• Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs. A pregnancy test is required for female
patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation
Anaplastic Kidney Wilms Tumor, Recurrent Kidney Wilms Tumor, Stage II Kidney Wilms Tumor, Stage III Kidney Wilms Tumor, Stage IV Kidney Wilms Tumor, Kidney
Inotuzumab Ozogamicin and Blinatumomab in Treating Patients With Newly Diagnosed, Recurrent, or Refractory CD22-Positive B-Lineage Acute Lymphoblastic Leukemia
This phase II trial studies how well inotuzumab ozogamicin and blinatumomab work in treating
patients with CD22-positive B-lineage acute lymphoblastic leukemia that is newly diagnosed,
has come back, or does not respond to treatment. Immunotherapy with monoclonal antibodies,
such as inotuzumab ozogamicin and blinatumomab, may help the body's immune system attack the
cancer, and may interfere with the ability of tumor cells to grow and spread.
Ryan Mattison, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03739814
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Inclusion Criteria:
• Pre-registration Eligibility Criteria (Step 0)
• Submission of bone marrow aspirate and peripheral blood for MRD analysis is mandatory
prior to registration; the bone marrow sample should be from the first aspiration
(i.e. first pull). Aspirate needle should be redirected if needed to get first pull
bone marrow aspirate. It should be initiated as soon as possible after
pre-registration. The specimens should be sent to the HEME Biobank.
• Lumbar Puncture (Spinal Tap) and Intrathecal Methotrexate:
• Patients may receive the day 1 of course IA dose of intrathecal (IT)
methotrexate during the prior-to-registration lumbar puncture (or the venous
line placement) to avoid a second lumbar puncture. If the dose is
administered prior to registration, then systemic chemotherapy must begin
within 7 days of this IT chemotherapy.
• Registration Eligibility Criteria (Step 1)
• Morphologic diagnosis of precursor B-cell acute lymphoblastic leukemia (ALL) based on
World Health Organization (WHO) criteria. Patients with Burkitt lymphoma/leukemia are
not eligible.
• CD22-positive disease defined as CD22 expression by >= 20% of lymphoblasts by local
hematopathology evaluation.
• Philadelphia chromosome/BCR-ABL1-negative ALL by cytogenetics, fluorescence in situ
hybridization (FISH), and/or polymerase chain reaction (PCR). If any test is positive
for Philadelphia chromosome/BCR-ABL1, then the patient is ineligible.
• No active central nervous system (CNS) leukemia (i.e. only CNS-1 disease allowed).
Active CNS leukemia is defined as morphologic evidence of lymphoblasts in the
cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease
within 28 days prior to registration, symptomatic CNS leukemia (i.e. cranial nerve
palsies or other significant neurological dysfunction) within the 28 days prior to
registration, and/or known asymptomatic parenchymal CNS mass lesions; see below for
additional guidance. Prophylactic intrathecal medication alone is not an exclusion.
• Categories of CNS Involvement for CNS Evaluation Prior to Registration:
• CNS 1: CSF has < 5 WBC/uL with cytospin negative for blasts; or >= 10 red
blood cell (RBC)/uL with cytospin negative for blasts.
• CNS 2: CSF has < 5 WBC/uL with cytospin positive for blasts; or >= 10 RBC/uL
with cytospin positive for blasts; or >= 10 RBC/uL, WBC/uL >= 5 but less
than Steinherz/Bleyer algorithm with cytospin positive for blasts (see
below).
• CNS 3: CSF has >= 5 WBC/uL with cytospin positive for blasts; or >= 10
RBC/uL, >= 5 WBC/uL and positive by Steinherz/Bleyer algorithm (see below);
or clinical signs of CNS leukemia (such as facial nerve palsy, brain/eye
involvement or hypothalamic syndrome). Steinherz/Bleyer Method of Evaluating
Initial Traumatic Lumbar Punctures:
• If the patient has leukemia cells in the peripheral blood and the
lumbar puncture is traumatic and contains >= 5 WBC/uL with blasts, the
following algorithm should be used to define CNS disease: CSF WBC/CSF
RBC > 2 x (Blood WBC/Blood RBC count)
• Patients with known or suspected testicular involvement by leukemia are allowed
provided that the patient receives concomitant scrotal/testicular radiotherapy.
• Unilateral or bilateral testicular enlargement should be assessed by ultrasound
or other imaging technique. Biopsy is recommended if clinical findings are
equivocal or suggestive of hydrocele or a non-leukemic mass, but further
assessments are per treating physician discretion.
• Not pregnant and not nursing.
• This study involves agents that have known genotoxic, mutagenic, and teratogenic
effects. Therefore, for women of childbearing potential only, a negative
pregnancy test done =< 7 days prior to registration is required.
• Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
• No unstable cardiac disease such as myocardial infarction, angina pectoris,
uncontrolled heart failure, or uncontrolled cardiac arrhythmia within 6 months of
registration.
• No impaired cardiac function, defined as left ventricular ejection fraction (LVEF) <
45% or New York Heart Association (NYHA) stage III or IV congestive heart failure
(CHF).
• Patients with known human immunodeficiency virus (HIV) infection are eligible if they
have been on effective antiretroviral therapy with an undetectable viral load tested
within 6 months of registration.
• Patients with hepatitis B virus (HBV) are eligible only if they meet all the
following:
• On HBV-suppressive therapy.
• No evidence of active virus.
• No evidence of HBV-related liver damage.
• Patients with hepatitis C virus (HCV) are eligible only if they meet all the
following:
• Successfully completed complete-eradication therapy with undetectable viral load.
• No evidence of HCV-related liver damage.
• No history of clinically relevant neurologic disorder such as epilepsy, seizure,
aphasia, stroke, severe brain injury, structural brain abnormality, benign brain
tumor, dementia, Parkinson's disease, movement disorder, cerebellar disease, or other
significant CNS abnormalities.
• No prior additional malignancy (i.e. in addition to ALL) except adequately treated
basal- or squamous-cell skin cancer, in situ cervical cancer, stage I or II cancer
from which the patient is currently in complete remission, or any other cancer from
which the patient has been disease-free for >= 2 years.
• No history of clinically significant ventricular arrhythmia, unexplained non-vasovagal
syncope, or chronic bradycardic states such as sinoatrial block or higher degree of
atrioventricular block unless a permanent pacemaker has been implanted.
• No history of chronic liver disease, including cirrhosis.
• No history of sinusoidal occlusion syndrome/veno-occlusive disease of the liver.
• No uncontrolled infection or recent history (within 4 months prior to registration) of
deep tissue infections such as fasciitis or osteomyelitis.
• Total bilirubin, serum =< 1.5 x upper limit of normal (ULN)*
• Except in the event of: 1) Gilbert disease, in which case total bilirubin must be
=< 2 x ULN, or 2) elevated bilirubin believed by investigator to be due to
leukemic infiltration, in which case total bilirubin must be =< 2 x ULN.
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
• Creatinine, serum =< 1.5 ULN OR creatinine clearance >= 40 mL/min
• QT interval by Fridericia's correction formula (QTcF) =< 470 msec
• Cohort 1 Patients Only
• Age >= 60 years.
• No prior treatment for ALL except a single dose of intrathecal chemotherapy,
corticosteroids, hydroxyurea, and/or leukapheresis to reduce peripheral blast count
and prevent ALL complications. Allowed therapy may be administered for no more than 14
days and must be completed >= 24 hours prior to the initiation of protocol therapy.
• No plan for allogeneic or autologous hematopoietic cell transplantation (HCT).
• Cohort 2 Patients Only:
• Age >= 18 years.
• Relapsed or refractory disease in salvage 1 or 2.
• No isolated extramedullary relapse.
• Prior allogeneic HCT permitted.
• Patients with prior allogeneic HCT must have completed transplantation >= 4 months
prior to registration.
• Patients with prior allogeneic HCT must have no evidence of graft-versus-host disease
and must have completed immunosuppressive therapy >= 30 days prior to registration.
• Prior treatment with inotuzumab ozogamicin, blinatumomab, other CD22-directed therapy,
or other CD19-directed therapy is not allowed.
• Prior treatment with rituximab must be completed >= 7 days prior to registration.
• Prior treatment with other monoclonal antibodies must be completed >= 6 weeks prior to
registration.
• Prior treatment for ALL must be completed >= 14 days prior to registration with the
following exceptions: intrathecal chemotherapy, hydroxyurea, corticosteroids,
6-mercaptopurine, methotrexate, vincristine, and/or leukapheresis to reduce
circulating absolute lymphoblast count to =< 10,000/uL or prevent complications
related to ALL are allowed but must be completed >= 24 hours prior to the initiation
of protocol therapy.
• Patients should have resolution of any acute non-hematologic toxicities of prior
therapy to National Cancer Institute (NCI) Common Terminology Criteria for Adverse
Events (CTCAE) version (v)5.0 grade =< 1.
• Peripheral blood absolute lymphoblast count =< 10,000/uL (treatment allowed as above
to reduce blast count to =< 10,000/uL)
B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative, Recurrent B Acute Lymphoblastic Leukemia, Refractory B Acute Lymphoblastic Leukemia, Lymphoid Leukemia, Leukemia
Intravesical Photodynamic Therapy ("PDT") in BCG-Unresponsive/Intolerant Non-Muscle Invasive Bladder Cancer ("NMIBC") Patients
This is a phase II, open-label, single-arm, multi-center Study conducted in Canada and the
United States. Patients with NMIBC CIS (with or without resected papillary disease (Ta, T1))
that are considered Bacillus Calmette-Guerin ("BCG")-Unresponsive or who are intolerant to
BCG therapy. BCG-Unresponsive is at least one of the following: At least five of six doses of
an initial induction course plus at least two of three doses of maintenance therapy; or, at
least five of six doses of an initial induction course plus at least two of six doses of a
second induction course. Patients experiencing disease relapse within 12 months after
finishing the second course of BCG therapy are considered BCG-Unresponsive. The Study will
consist of approximately 100 to 125 patients who will undergo two (2) PDT treatments
employing 0.70 mg/cm^2 of Ruvidar® (TLD-1433) at Day 0 and Day 180.
Kyle Richards, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03945162
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Inclusion Criteria:
1. Be willing and able to provide a written Informed Consent Form ("ICF") for the Study.
2. Be > 18 years of age on day of signing ICF.
3. Have histologically confirmed NMIBC CIS via biopsy with/without resected papillary
disease (Ta, T1) (high grade) using the 2004 World Health Organization ("WHO") /
International Society of Urologic Pathology classification system. The most recent
cystoscopy / TURBT must have been performed within 12 weeks of the Study Treatment
date to confirm: histology, grade and stage.
4. Intolerant to BCG or considered BCG-Unresponsive, which is at least one of the
following:
• At least five of six doses of an initial induction course, plus at least two of
three doses of maintenance therapy, or
• At least five of six doses of an initial induction course, plus at least two of
six doses of a second induction course.
5. Are not candidates for cystectomy on medical grounds or refuse radical cystectomy.
6. Have an Eastern Cooperative Oncology Group ("ECOG") performance score of 0 to 2.
7. Have satisfactory bladder function. Ability to retain Study Drug for a minimum of 60
minutes.
8. Are available for the duration of the Study including follow-up (approximately 15
months).
9. Female patients of childbearing potential must have a negative Human Chorionic
Gonadotropin ("HCG") pregnancy test taken during the screening visit and confirmed
prior to the Study Treatment.
10. Female patients of childbearing potential must be willing to use 2 methods of birth
control (i.e.: oral contraceptive, pills, diaphragm or condoms) or be surgically
sterile, or abstain from heterosexual activity for two weeks after the Study
Treatment. Patients of childbearing potential are those who have not been surgically
sterilized or have not been free from menses for >1 year.
Exclusion Criteria:
1. Past or current muscle invasive (i.e.: T2, T3, T4) or metastatic urothelial carcinoma.
2. Has concurrent extravesical (i.e.: urethra, ureter, renal pelvis, prostate or
prostatic ducts) non-muscle invasive transitional cell carcinoma of the urothelium.
(confirmed by staging to exclude extravesical disease, which may include radiological
imaging and/or biopsy) within 3 months of enrollment:
If previous work up occurred more than 3 months prior to enrollment, staging for
extravesical disease must be repeated prior to enrolment in order to determine
eligibility.
3. Active gross hematuria.
4. Have a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
skin that has undergone potentially curative therapy, in situ cervical cancer or
localized prostate cancer under active surveillance with Gleason 6 disease. A history
of prostate cancer that was treated with definitive intent (surgically or through
radiation therapy) is acceptable, provided that the following criteria are met: Stage
T2N0M0 or lower Prostate-Specific Antigen ("PSA") undetectable for 2 years while off
androgen deprivation therapy or no more than 2 consecutive rising PSAs.
5. Have a history or current evidence of any condition, therapy, surgery or laboratory
abnormality that, in the opinion of the PI, might confound the results of the Study,
interfere with the patient's participation in the Study, or is not in the best
interest of the patient to participate.
6. Currently receiving treatment with a prohibited concomitant therapy (refer to 12.2.1,
Prohibited Medications).
7. Participated in a study with an investigational agent or device within 1 month from
the first dose of current Study treatment.
8. Prior treatment with an intravesical chemotherapeutic agent within 1 month of the
first dose of current Study Drug, with the exception of a single perioperative dose of
chemotherapy immediately post-TURBT (not considered treatment).
9. Have an active infection requiring systemic therapy, including active or intractable
Urinary Tract Infection ("UTI"), not resolved prior to the procedure.
10. Has any contraindication to general or spinal anesthesia.
11. Is pregnant or breastfeeding within the projected duration of Study II, starting with
the screening visit through to two weeks following the second Ruvidar® (TLD-1433)
instillation.
Non-Muscle Invasive Bladder Cancer ("NMIBC") Unresponsive/Intolerant to BCG, Urinary Bladder, Bladder
A Study of Encorafenib Plus Cetuximab With or Without Chemotherapy in People With Previously Untreated Metastatic Colorectal Cancer
The purpose of this study is to evaluate two study medicines (encorafenib plus cetuximab)
taken alone or together with standard chemotherapy for the potential treatment of colorectal
cancer that:
- has spread to other parts of the body (metastatic);
- has a certain type of abnormal gene called "BRAF"; and
- has not received prior treatment.
Participants in this study will receive one of the following study treatments:
- Encorafenib plus cetuximab: These participants will receive encorafenib by mouth at home
every day and cetuximab once every two weeks by intravenous (IV) infusion (an injection
into the vein) at the study clinic.
- Encorafenib plus cetuximab with chemotherapy: These participants will receive
encorafenib and cetuximab in the way described in the bullet above. Additionally, they
will receive standard chemotherapy by IV infusion and oral treatment at home.
- Chemotherapy alone: These participants will receive chemotherapy, the standard treatment
for this condition, by IV infusion at the study clinics and oral treatment at home.
This study is currently enrolling participants who will receive either encorafenib plus
cetuximab with chemotherapy or chemotherapy alone.
The study team will monitor how each participant responds to the study treatment for up to
about 3 years.
Dustin Deming, MD
All
16 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04607421
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Inclusion Criteria:
• Safety Lead-In = Male/female ≥ 18 years old
• Phase 3 and Cohort 3: Male/female ≥ 16 years old (where permitted locally)
• Histologically or cytologically confirmed Stage IV CRC that contains BRAF V600E
mutation
• Prior systemic treatment in metastatic setting: 0-1 regimens for Safety Lead In; none
for Phase 3 and Cohort 3. (Note: Prior adjuvant or neoadjuvant therapy considered
metastatic treatment if relapse/metastasis < 6 month from end of adj/neoadjuvant
treatment )
• Measurable disease (Phase 3 and Cohort 3)/ Measurable or evaluable disease (Safety
Lead-in)
• ECOG PS 0-1
• Adequate organ function
Exclusion Criteria:
• Tumors that are locally confirmed or unknown MSI-H or dMMR unless participant is
ineligible to receive immune checkpoint inhibitors due to a pre-existing medical
condition
• Active bacterial or viral infections in 2 weeks prior to starting dosing
• Symptomatic brain metastases
Expanded Access Protocol (EAP) for Subjects Receiving Idecabtagene Vicleucel That is Nonconforming for Commercial Release
This study is designed to evaluate the safety and efficacy of nonconforming idecabtagene
vicleucel (ide-cel) in subjects with multiple myeloma per the approved prescribing
information. This is an expanded access protocol (EAP) to be conducted at Risk Evaluation and
Mitigation Strategies (REMS) qualified sites approved for commercial administration of
idecabtagene vicleucel and where the EAP is authorized to be conducted for use of
nonconforming idecabtagene vicleucel.
Non-conforming idecabtagene vicluecel is idecabtagene vicleucel that does not meet commercial
release specifications but may be acceptable for use as an investigational product in the
Expanded Access Protocol setting.
Natalie Callander, MD
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT04771078
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Inclusion Criteria:
1. Subject has multiple myeloma, 18 years of age or older and subject or legally
authorized representative is able to sign the informed consent form.
2. Subject had a subject-specific batch of idecabtagene vicluecel manufactured intended
for commercial treatment; however, the final manufactured product was nonconforming
and did not meet commercial release criteria. The Sponsor has determined that the
nonconforming idecabtagene vicleucel may be released for use under the Expanded Access
Protocol.
3. Remanufacturing is deemed not feasible or clinically inappropriate per assessment of
the treating physician in discussion with the subject.
4. Subject is clinically stable, has recovered from any prior toxicities prior to
receiving lymphodepleting chemotherapy, and has adequate bone marrow function to
receive lymphodepleting chemotherapy
5. Females of childbearing potential must:
1. Have a negative pregnancy test as verified by the treating physician within 7
days prior to the first dose of lymphodepleting chemotherapy following
institutional testing methodology practices. This applies even if the subject
practices true abstinence from heterosexual contact.
2. Either commit to true abstinence from heterosexual contact or agree to use, and
be able to comply with, effective contraception without interruption.
Contraception methods must include 1 highly effective method from screening until
at least 12 months after the lymphodepleting chemotherapy.
3. Agree to abstain from breastfeeding during study participation and for at least
12 months following lymphodepleting chemotherapy.
4. There are insufficient exposure data to provide any recommendation concerning the
duration of contraception and the abstaining from breastfeeding following
treatment with nonconforming idecabtagene vicluecel. Any decision regarding
contraception and breastfeeding after infusion should be discussed with the
treating physician.
6. Male subjects must:
1. Practice true abstinence or agree to use a condom during sexual contact with a
pregnant female or a female of childbearing potential for at least 12 months
after lymphodepleting chemotherapy even if the subject has undergone a successful
vasectomy.
2. There are insufficient exposure data to provide any recommendation concerning the
duration of contraception following treatment with nonconforming idecabtagene
vicluecel. Any decision regarding contraception after infusion should be
discussed with the treating physician.
Subject must agree to not donate blood, organs, tissue, sperm or semen and egg cells for
usage in other individuals for at least 1 year following lymphodepleting chemotherapy.
There are insufficient exposure data to provide any recommendation concerning the duration
of refraining from tissue donation following treatment with nonconforming idecabtagene
vicluecel. Therefore, participants treated with nonconforming idecabtagene vicluecel should
not donate blood, organs, tissues, and cells for transplantation.
Exclusion Criteria:
1. Subject has a hypersensitivity to the active substance or to any of the excipients.
2. Subject should not experience a significant worsening in clinical status that would,
in the opinion of the treating physician, either increase the risk of AEs associated
with lymphodepleting chemotherapy or exclude them from treatment with nonconforming
idecabtagene vicluecel.
3. Subject has any significant medical condition, laboratory abnormality, or psychiatric
illness, sociologic or geographic condition that would prevent the subject from
participating in the Expanded Access Protocol, complying with protocol requirements or
confound the ability to interpret the data in the Investigator's judgement.
4. Subject has any condition and/or laboratory abnormality that places the subject at
unacceptable risk if he/she were to participate in the Expanded Access Protocol based
on the Investigator's judgement.
5. Pregnant or nursing women or has intention of becoming pregnant during the study.
A Study to Compare Treatment With the Drug Selumetinib Alone Versus Selumetinib and Vinblastine in Patients With Recurrent or Progressive Low-Grade Glioma
This phase III trial investigates the best dose of vinblastine in combination with
selumetinib and the benefit of adding vinblastine to selumetinib compared to selumetinib
alone in treating children and young adults with low-grade glioma (a common type of brain
cancer) that has come back after prior treatment (recurrent) or does not respond to therapy
(progressive). Selumetinib is a drug that works by blocking a protein that lets tumor cells
grow without stopping. Vinblastine blocks cell growth by stopping cell division and may kill
cancer cells. Giving selumetinib in combination with vinblastine may work better than
selumetinib alone in treating recurrent or progressive low-grade glioma.
Kenneth Desantes, M.D.
All
2 Years to 25 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04576117
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Inclusion Criteria:
• Feasibility phase: patients must be >= 2 years and =< 21 years of age at the time of
enrollment
• Efficacy phase: patients must be >= 2 years and =< 25 years of age at the time of
enrollment
• All patients > 21 years of age at the time of enrollment must have had initial
diagnosis of low-grade glioma by 21 years of age
• Patients must have a body surface area (BSA) of >= 0.5 m^2 at enrollment
• Patients must have eligibility confirmed by rapid central pathology and central
molecular screening reviews performed on APEC14B1
• Non-neurofibromatosis type 1 (non-NF1), non-tuberous sclerosis complex (non-TSC)
low-grade glioma (LGG) without a BRAFV600E or IDH1 mutation
• Patients must have progressive or recurrent LGG. Note: Biopsy may be at either
initial diagnosis or recurrence
• Patients must have measurable disease, defined as having a two-dimensional
measurable tumor volume of >= 1 cm^2
• Tumor size will be measured to include both solid and cystic components of
the tumor (whether or not tumor is enhancing) + fluid attenuated inversion
recovery (FLAIR) signal
• Eligible histologies will include all tumors considered low-grade glioma or
low-grade astrocytoma (World Health Organization [WHO] grade 1 and II) by the WHO
Classification of Tumors of the Central Nervous System •4th Edition Revised,
with the exception of subependymal giant cell astrocytoma
• Patients with metastatic disease or multiple independent primary LGGs are
eligible
• Patients must be progressive or recurrent after having been treated with at least one
prior tumor-directed therapy before enrollment
• Patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry
onto this study (4 weeks if prior nitrosourea);
• Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy
with a biologic agent;
• Radiation therapy (RT): >= 2 weeks (wks) for local palliative RT (small port); >=
6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of
pelvis; >= 6 wks must have elapsed if other substantial bone marrow (BM)
radiation;
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody,
and toxicity related to prior antibody therapy must be recovered to =< grade 1;
• MEK inhibitor or vinblastine: Must not have received treatment with a MEK
inhibitor or vinblastine within 6 months of study enrollment
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^ 2 or a serum creatinine based on age/gender as follows (within 7 days
prior to enrollment):
• 2 to < 6 years: 0.8 mg/dL (male) 0.8 mg/dL (female)
• 6 to < 10 years: 1 mg/dL (male) 1 mg/dL (female)
• 10 to < 13 years: 1.2 mg/dL (male) 1.2 mg/dL (female)
• 13 to < 16 years: 1.5 mg/dL (male) 1.4 mg/dL (female)
• >= 16 years: 1.7 mg/dL (male) 1.4 mg/dL (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed on study
regardless of their total and indirect [unconjugated] bilirubin levels as long as
their direct [conjugated] bilirubin is < 3.1 mg/dL)
• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L
(within 7 days prior to enrollment)
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
value of 45 U/L
• Albumin >= 2 g/L (within 7 days prior to enrollment)
• Left ventricular ejection fraction (LVEF) >= 53% (or institutional normal; if the LVEF
result is given as a range of values, then the upper value of the range will be used)
by echocardiogram (within 4 weeks prior to enrollment)
• Corrected QT interval (QTc interval) =< 450 msec by electrocardiogram (EKG) (within 4
weeks prior to enrollment)
• Absolute neutrophil count >= 1,000/uL (unsupported) (within 7 days prior to
enrollment)
• Platelets >= 100,000/uL (unsupported) (within 7 days prior to enrollment)
• Hemoglobin >= 8 g/dL (may be supported) (within 7 days prior to enrollment)
• Patients with a known seizure disorder should be stable and should not have
experienced a significant increase in seizure frequency within 2 weeks prior to
enrollment
• Stable neurological examination for >= 1 week
• HYPERTENSION:
• Patients 2-17 years of age must have a blood pressure that is =< 95th percentile
for age, height, and gender at the time of enrollment (with or without the use of
anti-hypertensive medications);
• Patients >= 18 years of age must have a blood pressure =< 130/80 mmHg at the time
of enrollment (with or without the use of anti-hypertensive medications)
• Note for patients of all ages: Adequate blood pressure can be achieved using
medication for the treatment of hypertension
• All patients must have ophthalmology toxicity assessments performed within 4 weeks
prior to enrollment
• For all patients, an MRI of the brain (with orbital cuts for optic pathway tumors)
and/or spine (depending on the site[s] of primary disease) with and without contrast
must be performed within 4 weeks prior to enrollment
• Note: If surgical resection or biopsy is performed at the time of progression or
recurrence, a post-operative MRI is required
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age
• Patients must have the ability to swallow whole capsules
Exclusion Criteria:
• Prior therapy with vinblastine and/or a MEK inhibitor is permitted, with the following
exceptions:
• Patients must not have had progressive disease while on therapy with vinblastine
or a MEK inhibitor;
• Patients must not have discontinued vinblastine or selumetinib due to toxicity
• Patients with a concurrent malignancy or history of treatment (other than surgery) for
another tumor within the last year are ineligible
• Patients with diffuse intrinsic pontine tumors as seen on MRI (> 2/3 of pons
involvement on imaging) are not eligible even if biopsy reveals grade I/II histology
• Patients may not be receiving any other investigational agents
• Patients must not have known hypersensitivity to selumetinib, vinblastine, or similar
compounds
• CYP3A4 agents: Patients must not have received fluconazole or drugs that are strong
inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment
• Patients with any serious medical or psychiatric illness/condition, including
substance use disorders or ophthalmological conditions, likely in the judgment of the
investigator to interfere or limit compliance with study requirements/treatment
• Patients who, in the opinion of the investigator, are not able to comply with the
study procedures are not eligible
• PRE-EXISTING CONDITIONS (CARDIAC):
• Known genetic disorder that increases risk for coronary artery disease. Note: The
presence of dyslipidemia in a family with a history of myocardial infarction is
not in itself an exclusion unless there is a known genetic disorder documented;
• Symptomatic heart failure
• New York Heart Association (NYHA) class II-IV prior or current
cardiomyopathy
• Severe valvular heart disease
• History of atrial fibrillation
• PRE-EXISTING CONDITIONS (OPHTHALMOLOGIC CONDITIONS):
• Current or past history of central serous retinopathy
• Current or past history of retinal vein occlusion or retinal detachment
• Patients with uncontrolled glaucoma
• If checking pressure is clinically indicated, patients with intraocular
pressure (IOP) > 22 mmHg or upper limit of normal (ULN) adjusted by age are
not eligible
• Any multivitamin containing vitamin E must be stopped prior to study enrollment even
if it contains less than 100% of the daily recommended dosing for vitamin E
• Surgery within 2 weeks prior to enrollment, with the exception of a surgical biopsy,
placement of a vascular access device or cerebrospinal fluid (CSF) diverting procedure
such as endoscopic third ventriculostomy (ETV) and ventriculoperitoneal (VP) shunt
• Note: Patients must have healed from any prior surgery
• Patients who have an uncontrolled infection are not eligible
• Female patients who are pregnant are not eligible since fetal toxicities and
teratogenic effects have been noted for several of the study drugs. A pregnancy test
is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation and for
12 weeks after stopping study therapy are not eligible
• Note: Women of child-bearing potential and males with sexual partners who are
pregnant or who could become pregnant (i.e., women of child-bearing potential)
should use effective methods of contraception for the duration of the study and
for 12 weeks after stopping study therapy to avoid pregnancy and/or potential
adverse effects on the developing embryo
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Recurrent Low Grade Astrocytoma, Recurrent WHO Grade 2 Glioma, Refractory Low Grade Astrocytoma, Refractory Low Grade Glioma, Refractory WHO Grade 1 Glioma, Brain and Nervous System, Brain/Central Nervous System
This is an expanded access protocol that will be conducted at sites qualified and approved to
treat subjects with lisocabtagene maraleucel. Sometimes when lisocabtagene maraleucel is
manufactured the drug does not pass all the testing results to be called lisocabtagene
maraleucel. When this happens the drug is called nonconforming lisocabtagene maraleucel. The
expanded access protocol will be used to allow subjects to receive nonconforming
lisocabtagene maraleucel only if the potential benefit is better than the potential risk.
This expanded access protocol is restricted to those subjects who were prescribed
lisocabtagene maraleucel as part of their routine care.
Subjects will first receive a lymphodepleting chemotherapy regimen and then be treated with
nonconforming lisocabtagene maraleucel as the treatment plan.
Vaishalee Kenkre, MD
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT04400591
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Inclusion Criteria:
1. Subject and/or LAR must understand and voluntarily sign an informed consent form prior
to any study-related assessments/procedures being conducted.
2. Subject has relapsed and/or refractory large B-cell lymphoma and is, per the treating
physician assessment, eligible for treatment with lisocabtagene maraleucel per the
approved prescribing information.
3. Subject is ≥ 18 years of age at the time of signing the informed consent form.
4. Subject had a specific batch of lisocabtagene maraleucel manufactured intended for
commercial treatment; however, the final manufactured product did not meet commercial
release criteria.
5. Remanufacturing (eg, repeat leukapheresis and manufacturing) is deemed not feasible or
clinically inappropriate per assessment of the treating physician in discussion with
the subject.
6. Subject is clinically stable, has recovered from any toxicities prior to receiving
lymphodepleting chemotherapy, and has adequate bone marrow function to receive
lymphodepleting chemotherapy. The treating physician is advised to contact Medical
Monitor in the event there is any concern regarding administration of lymphodepleting
chemotherapy.
7. Females of childbearing potential must:
1. Have a negative pregnancy test as verified by the treating physician within 7
days prior to the first dose of lymphodepleting chemotherapy following
institutional testing methodology practices. This applies even if the subject
practices true abstinence from heterosexual contact.
2. Either commit to true abstinence from heterosexual contact or agree to use, and
be able to comply with, effective contraception without interruption.
Contraception methods must include 1 highly effective method from screening until
at least 12 months after the nonconforming lisocabtagene maraleucel
administration.
3. Agree to abstain from breastfeeding during study participation and for at least
12 months following nonconforming lisocabtagene maraleucel administration.
4. There are insufficient exposure data to provide any recommendation concerning the
duration of contraception and the abstaining from breastfeeding following
treatment with lisocabtagene maraleucel. Any decision regarding contraception and
breastfeeding after infusion should be discussed with the treating physician.
8. Male subjects must:
1. Practice true abstinence or agree to use a condom during sexual contact with a
pregnant female or a female of childbearing potential for at least 12 months
after nonconforming lisocabtagene maraleucel administration even if the subject
has undergone a successful vasectomy.
2. There are insufficient exposure data to provide any recommendation concerning the
duration of contraception following treatment with lisocabtagene maraleucel. Any
decision regarding contraception after infusion should be discussed with the
treating physician
9. Subject must agree to not donate blood, organs, tissue, sperm or semen and egg cells
for usage in other individuals for at least 1 year following nonconforming
lisocabtagene maraleucel administration.
Exclusion Criteria:
1. Subject has a hypersensitivity to the active substance or to any of the excipients.
2. Subject should not experience a significant worsening in clinical status that would,
in the opinion of the treating physician, either increase the risk of adverse events
associated with lymphodepleting chemotherapy, or exclude them from treatment with
nonconforming lisocabtagene maraleucel.
3. Subject has any significant medical condition, laboratory abnormality, or psychiatric
illness, sociologic or geographic condition that would prevent the subject from
participating in the Expanded Access Protocol complying with protocol requirements in
the Investigator's judgement.
4. Subject has any condition and/or laboratory abnormality that places the subject at
unacceptable risk if he/she were to participate in the Expanded Access Protocol based
on the Investigator's judgement
5. Pregnant or nursing women or has intention of becoming pregnant during the study.
6. Subjects with central nervous system (CNS)-only involvement by malignancy (note:
subjects with secondary CNS involvement are allowed on study).
7. Subject has active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
infection at the time of pretreatment evaluation
8. Subject has uncontrolled systemic fungal, bacterial, viral or other infection despite
appropriate antibiotics or other treatment at the time of nonconforming lisocabtagene
maraleucel administration.
9. Subject has presence of acute or chronic graft-versus-host disease (ie, GVHD)
10. Use of the following:
1. Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or
equivalent) within 72 hours prior to nonconforming lisocabtagene maraleucel
administration. Physiologic replacement, topical, and inhaled steroids are
permitted.
2. Low dose chemotherapy (eg, vincristine, rituximab, cyclophosphamide ≤ 300
mg/m2)given after leukapheresis to maintain disease control must be stopped ≥ 7
days prior to lymphodepleting chemotherapy.
3. Cytotoxic chemotherapeutic agents that are not considered lymphotoxic (see below)
within 1 week of LD chemotherapy. Oral chemotherapeutic agents, including
lenalidomide and ibrutinib, are allowed if at least 3 half-lives have elapsed
prior to lymphodepleting chemotherapy.
4. Donor lymphocyte infusions within 6 weeks of nonconforming lisocabtagene
maraleucel administration.
Non-Hodgkin's Lymphoma, Lymphoma, Lymphoma, Large B-Cell, Diffuse
DNA-Guided Second Line Adjuvant Therapy For High Residual Risk, Stage II-III, Hormone Receptor Positive, HER2 Negative Breast Cancer (DARE)
A randomized, Phase II trial of circulating tumor DNA-guided second line Adjuvant therapy for
high Residual risk, stage II-III, Estrogen Receptor positive, HER-2 negative breast cancer
(DARE)
Mark Burkard, MD, PhD
All
Not specified
Phase 2
This study is NOT accepting healthy volunteers
NCT04567420
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Inclusion Criteria:
•4.1.1. Stage II or III, HER2 negative, ER positive invasive breast cancer in male or
female patients. For this study, ER positivity is defined as equal to or greater than 10%
ER positivity by immunohistochemistry, regardless of progesterone receptor (PR) status.
Patients with PR positive but ER negative cancer are not eligible. HER2 negative status is
defined as per the ASCO/CAP 2018 practice guidelines.
(i) if patients have synchronous bilateral ER+ breast cancer tissue from both sites should
be submitted to Natera to perform ctDNA testing.
(ii) patients with multifocal/multicentric tumors are eligible and the largest focus of
cancer should be submitted for testing. All tumors must meet pathological criteria for
HER2-and ER+ status.
(iii) For. patients who received neoadjuvant therapy and have discordant ER and HER2
results between the diagnostic biopsy (pre-treatment) and surgical pathology (post
neoadjuvant therapy), the ER+ and HER2- status of the post-treatment specimen determine
eligibility.
4.1.2. Currently taking an aromatase inhibitor, or tamoxifen, as adjuvant endocrine therapy
and have completed at least 6 months (i.e. 24 weeks), but no more than 7 years with 3 more
years planned, of endocrine therapy. Patients may register for the screening phase of the
study within the first 6 months of adjuvant endocrine therapy but the first ctDNA testing
must occur at, or after, 6 months of endocrine therapy.
(i) Adjuvant bisphosphonate therapy is allowed. (ii) LHRH analogues are required for
premenopausal patients randomized to receive fulvestrant.
4.1.3. Clinical and pathological high risk for recurrence defined as any one of the
following: (i) At least a 15% predicted risk of death within 10 years using ePREDICT V2.1
(https://breast.predict.nhs.uk/tool), or (ii) At least 15% or greater risk of distant
metastasis within 10 years using RSPC,
(https://tools.genomichealth.com/Tools/RSPCTool.aspx), or (iii) At least 15% or greater
risk of distant metastasis within 10 years CTS5 (https://www.cts5-calculator.com) for
patients who have completed a minimum of 4 years of adjuvant endocrine therapy, or (iv)
Tumor size > 5 cm, regardless of lymph node status, or (v) 1-3 involved axillary lymph
nodes and at least one of the following;
• Tumor size > 3 cm,
• High histological grade (e.g. grade 3).
• High genomic risk defined as Oncotype Dx Recurrence Score >26, EndoPredict score >4,
Prosigna risk of recurrence score ≥ 60, or Mammaprint high risk.
(vi) Patients who have received pre-operative (neoadjuvant) chemotherapy must have either:
• greater than or equal to 3 cm invasive residual cancer regardless of nodal status AND
grade 3 disease or RS>26/MammPrint High/Prosigna high/Endopredict high status, or
• greater than or equal to 1 cm invasive residual cancer (ypT1c) and at least 1 positive
lymph node (ypN+) AND grade 3 disease, or RS>26, or MammPrint High, or Endopredict
high or Prosigna high status.
4.1.4. Patients must have FFPE tissue from the primary tumor available for submission to
Natera to perform ctDNA assay (see Appendix B for tissue submission instructions).
4.1.5. Signed and dated informed consent, including willingness to be randomized to
standard of care versus fulvestrant + palbociclib.
4.2 Inclusion and exclusion criteria for treatment randomization
Inclusion criteria for randomization
4.2.1. ctDNA positivity by the Signatera assay, defined as 2 of the 16 cancer specific
markers positive in plasma.
4.2.2. Patients with positive Signatera results obtained in the context of commercial
testing, outside of the screening phase of this trial, are also eligible for randomization
if they meet other eligibility criteria.
4.2.3. No evidence of metastatic disease on CT scan of the chest, abdomen and pelvis.
• If imaging, after review with a radiologist, is low probability for metastatic
disease, patients may proceed to randomization.
• Patients with suspicious but inconclusive imaging results should undergo a diagnostic
biopsy, if biopsy is negative patients are eligible for randomization.
• Patients with positive imaging that is conclusive of metastatic disease, or with
biopsy proven metastatic disease, are not eligible for randomization.
4.2.4. Pre-menopausal women and male patients must be willing to use an adequate method of
contraception for the duration of trial treatment and for 4 additional weeks after
completion of treatment in the control arm, and for 2 years after the last dose of
fulvestrant, if randomized into the experimental arm.
Post-menopausal status is defined as:
• Documented bilateral oophorectomy.
• Age ≥ 60 years.
• Age < 60 years and amenorrhoeic for ≥ 12 consecutive months and FSH and estradiol
levels in the post-menopausal range according to the institutional reference range for
post-menopausal.
Adequate contraception is defined as ONE highly effective form (i.e. abstinence, surgical
sterilization through bilateral tubal ligation, vasectomy), or TWO effective forms (e.g.
non-hormonal IUD and condom / occlusive cap with spermicidal foam / gel / film / cream /
suppository).
•Abstinence is to be interpreted as "true abstinence" for heterosexual intercourse and
therefore, "periodic abstinence" (e.g. calendar, symptothermal, post-ovulation methods) and
withdrawal (coitus interruptus) are not considered highly effective.
Exclusion Criteria
4.1.5. Prior or current treatment with fulvestrant, or current treatment with a CDK4/6
inhibitor, or treatment in the prior 12 months, or participants in the PENELOPE and PALLAS
clinical trials.
4.1.6. Patients cannot start participation in another therapeutic clinical trial for breast
cancer after enrollment in this trial.
4.1.7. Patients with current or past invasive cancer, other than breast cancer are not
eligible, except:
• Adequately treated basal or squamous cell carcinoma of the skin are eligible.
• Cancer survivors of previously diagnosed invasive cancer, who were treated with a
curative intent, have no evidence of disease recurrence for 5 years or more, and are
considered low risk for future recurrence by the treating physician are also eligible.
4.1.8. Patients with a second HER2 positive or triple negative synchronous breast cancer
are not eligible.
Exclusion criteria for randomization
4.2.5. Patients with known contraindications to receive fulvestrant and palbociclib or
those who are unable to tolerate these drugs are not eligible.
• Absolute neutrophil count less than <1000/mm3;
4.2.6. Any concurrent severe and uncontrolled medical condition that would, in the
Investigator' opinion cause unacceptable safety risks or compromise compliance with the
protocol including but not limited to:
• Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of oral medication (e.g. Crohn's disease, ulcerative diseases,
uncontrolled chronic nausea, vomiting, diarrhea, malabsorption syndrome, or small
bowel resection).
• History of pneumonitis, interstitial lung disease or pulmonary fibrosis.
• Known history of Human Immunodeficiency Virus (HIV) (testing is not mandatory).
• Known active Hepatitis B or Hepatitis C (testing is not mandatory).
• Females who are pregnant or breastfeeding.
• History of bleeding diathesis (i.e. disseminated intravascular coagulation, clotting
factor deficiency) that preclude the IM injections of fulvestrant or LHRH agonist as
applicable.
4.2.7 Patients taking any CYPC3A4 strong inducers and inhibitors, that cannot be changed.
Additional Support Program Via Text Messaging and Telephone-Based Counseling for Breast Cancer Patients Receiving Hormonal Therapy
This phase III trial compares an additional support program (text message reminders and/or
telephone-based counseling) with usual care in making sure breast cancer patients take their
endocrine therapy medication as prescribed (medication adherence). Medication adherence is
how well patients take the medication as prescribed by their doctors, and good medical
adherence is when patients take medications correctly. Poor medication adherence has been
shown to be a serious barrier to effective treatment for hormone receptor positive breast
cancer patients. Adding text message reminders and/or telephone-based counseling to usual
care may increase the number of days that patients take their endocrine therapy medication as
prescribed.
Toby Campbell, MD
Female
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04379570
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• Women with an initial pathologically confirmed diagnosis of stage I-III, hormone
receptor positive, HER2-neu negative, invasive breast cancer within 18 months prior to
enrollment
• Women who have undergone neo-adjuvant chemotherapy who have no residual invasive
disease post-surgery are eligible based on an initial pathologically confirmed
diagnosis
• Hormone receptor positive is defined as estrogen receptor (ER) and/or
progesterone receptor (PR) of > 1%
• HER2-neu negative is defined as 0-1+ by immunohistochemical (IHC) analysis, or
non-amplified by fluorescence in situ hybridization (FISH) analysis
• Patients must have received cancer-directed surgery, and/or completed all other
adjuvant therapy, except reconstruction
• Patients must have initiated an endocrine therapy drug within the 6 months prior to
registration, OR have received a prescription with stated intent to initiate within 6
weeks after registration
• No history of previous cancer as follows:
• Invasive or non-invasive breast cancer at any time
• Non-breast cancer, within the past 5 years, excluding non-melanoma skin cancer
• Patients must be willing to use a smart phone for study activities
• Patient is NOT to be deemed ineligible during the recruitment process if they do
not have a smart phone
• If a participant does not own a smart phone or has limited data or texting
capabilities or their smart phone cannot support the Alliance electronic patient
reported outcomes (ePRO) survey application (app), a smart phone and service can
be provided to the participant at no cost through the Ohio State University (OSU)
partnership with Verizon Wireless for the duration of the study activities
• The CRP is ONLY to discuss this option with those patients who self-identify a
phone-related barrier to participation, including: lack of a smart phone,
insufficient phone plan (minutes/text/data), or a smart phone incompatible with
the Alliance ePRO app
• For OSU -provided phones, charges will be paid by the grant through the
intervention period. At the end of the 12-month intervention period, patients
will be responsible for paying monthly fees, if continued service is desired. The
physical phones will belong to the patients at the end of their study activities
• Patients must be willing to use a Pillsy medication event monitoring system for the
duration of study participation
• In order to complete the mandatory patient-completed measures, participants must be
able to speak and read English
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, HER2 Negative Breast Carcinoma, Hormone Receptor Positive Breast Carcinoma, Invasive Breast Carcinoma, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage II Breast Cancer AJCC v8, Prognostic Stage III Breast Cancer AJCC v8, Breast
Study of TJ033721 in Subjects With Advanced or Metastatic Solid Tumors
This is an open label, multi-center, multiple dose Phase 1 study to evaluate the safety,
tolerability, MTD PK, and PD of TJ033721 in subjects with advanced or metastatic solid
tumors.
Jeremy Kratz, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT04900818
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Inclusion Criteria:
• Subjects with advanced or metastatic solid tumor in subjects whose disease has
progressed despite standard therapy, or who has no further standard therapy, or who is
unsuitable for available standard treatment options.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 with adequate
organ function
• Have known PD-L1 status with prior testing by immunohistochemistry and a corresponding
combined positive score (CPS)
For dose expansion study only:
• Advanced or metastatic gastric cancer, gastroesophageal junction carcinoma, and
esophageal adenocarcinoma without further standard therapy or unsuitable for available
standard treatment options.
• Must have CLDN18.2-positive tumor expression as determined by the CLDN18.2 IHC assay
Exclusion Criteria
• Prior exposure to CLDN18.2 -targeted therapy
• Prior exposure to 4-1BB agonists
• Second malignancy within the last 3 years with the exception of cutaneous squamous
cell carcinoma or cutaneous basal cell carcinoma or cervical carcinoma in situ
• Known active or chronic Hepatitis B or Hepatitis C, other hepatitides
• Unstable/active ulcer or digestive tract bleeding within 6 weeks
• Active autoimmune disease requiring systemic treatment within the past 2 years
• Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or
pneumonitis requiring treatment
• Known active CNS metastases and/or carcinomatous meningitis. Subjects with previously
treated brain metastases may participate provided they are clinically stable and
without requirement of steroid treatment for at least 14 days prior to first dose of
study treatment;
• New York Heart Association (NYHA) Class 3 or 4 congestive heart failure,
severe/unstable angina, myocardial infarction (MI), symptomatic congestive heart
failure, cerebrovascular accident, transient ischemic attack (TIA), arterial embolism,
pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA), deep vein
thrombosis, or coronary artery bypass grafting (CABG) in the previous 6 months
• Diagnosis of immunodeficiency such as known active HIV
• Any active infection requiring parenteral treatment
Solid Tumor, Advanced Cancer, Metastatic Cancer, Gastric Cancer, Gastroesophageal Junction Carcinoma, Esophageal Adenocarcinoma, Lip, Oral Cavity and Pharynx, Esophagus, Colon, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Melanoma, Skin, Kaposi's Sarcoma, Breast, Cervix, Corpus Uteri, Other Female Genital, Other Male Genital, Kidney, Eye and Orbit, Brain and Nervous System, Other Endocrine System, Ill-Defined Sites, Anal, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Ovary, Sarcoma, Uterus
Androgen Deprivation, With or Without pTVG-AR, and With or Without T-Cell Checkpoint Blockade, in Patients With Newly Diagnosed, High-Risk Prostate Cancer
The current protocol will examine the use of a plasmid DNA vaccine encoding AR, alone or with
T-cell checkpoint blockade, to induce and/or augment therapeutic T-cells following androgen
deprivation in patients with newly diagnosed prostate cancer scheduled to undergo
prostatectomy. Patients without evidence of metastatic disease, with tissue remaining from a
pre-treatment biopsy, and who are being considered for standard treatment by prostatectomy,
will be invited to participate and will be on study for up to 15 months.
Christos Kyriakopoulos, MD
Male
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04989946
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Inclusion Criteria:
• Histologically confirmed adenocarcinoma of the prostate
• Patients must be considered candidates for prostatectomy as per standard of care
• High-risk patients for recurrent disease, with high risk defined based on one of the
following criteria:
• Gleason score 7 and baseline serum prostate specific antigen (PSA) > 20 ng/mL
• Gleason score > 7
• Life expectancy of at least 12 months at screening
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate hematologic, renal and liver function as evidenced by the following within 4
weeks of day 1:
• Absolute neutrophil count (ANC) > 1000 / mm3
• HgB > 9.0 gm/dL independent of transfusion
• Platelets > 100,000 / mm3
• Creatinine < 2.0 mg/dL
• Aspartate aminotransferase (AST), Alanine transaminase (ALT) < 2.5 x
institutional upper limit of normal (ULN)
• Total bilirubin < 2x institutional ULN (NOTE: in subjects with Gilbert's
syndrome, if total bilirubin is >2x ULN, measure direct and indirect bilirubin
and if direct bilirubin is within normal range, subject may be eligible)
• No known history of HIV 1 and 2, HTLV-1, or active Hepatitis B or Hepatitis C
• Must have adequate tissue (ten 5µm unstained formalin-fixed paraffin-embedded (FFPE)
sections containing prostate cancer) remaining from pre-treatment diagnostic prostate
biopsy for research purposes
• Patients must be willing to undergo large-volume blood draws (up to 200mL per time
point) for the investigational component of this trial
• For those patients who are sexually active, they must be willing to use barrier
contraceptive methods during the period of treatment on this trial
• Patients must be informed of the experimental nature of the study and its potential
risks, and must sign an IRB-approved written informed consent form indicating such an
• Ability to comply with all study procedures and willingness to remain supine for 120
minutes during imaging
Exclusion Criteria:
• Small cell or other variant (non-adenocarcinoma) prostate cancer histology
• Prior treatment for prostate cancer, including androgen deprivation therapy (ADT),
orchiectomy, antiandrogens, ketoconazole, abiraterone acetate or enzalutamide
• Prior radiation to the prostate
• Patients may not be receiving other investigational agents or be receiving concurrent
anticancer therapy other than the treatment-prescribed androgen deprivation therapy
• Treatment with any of the following medications while on study is prohibited, washout
period not required except as indicated:
• Systemic corticosteroids (at doses over the equivalent of 10 mg prednisone daily)
•not permitted within 3 months of registration; inhaled, intranasal or topical
corticosteroids are acceptable
• PC-SPES
• Herbal supplements that have been shown to modulate testosterone or androgen
signaling (e.g. Saw Palmetto) are not allowed while on study
• Megestrol
• Ketoconazole
• 5-α-reductase inhibitors •patients already taking 5-α-reductase inhibitors prior
to 28 days prior to registration may stay on these agents throughout the course
of therapy, but these should not be started while patients are on study
• Diethylstilbesterol
• Any other non-study hormonal agent or supplement being used with the intent of
cancer treatment
• Major surgery within 4 weeks of registration is prohibited
• Active cardiac disease defined as active angina, symptomatic congestive heart failure,
or myocardial infarction within 6 months of registration
• Patients with known psychological or sociological conditions, addictive disorders or
family problems, which would preclude compliance with the protocol
• Patients who have undergone splenectomy
• Patients must not have other active malignancies other than non-melanoma skin cancers
or carcinoma in situ of the bladder, that have been adequately treated. Subjects with
a history of other cancers who have been adequately treated and have been
recurrence-free for > 3 years are eligible.
• Any other medical intervention or condition, which, in the opinion of the principle
investigator (PI) or treating physician, could compromise patient safety or adherence
with the study requirements over the primary 3-6 month treatment period.
• Patients who have concurrent enrollment on other phase I, II, or III investigational
treatment studies cannot be actively receiving treatment and the last dose cannot be
within 4 weeks.
• Patients who have received a live vaccine within 14 days prior to the first dose of
study treatment. Examples of live vaccines include, but are not limited to, the
following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever,
rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza
vaccines for injection are generally killed virus vaccines and are allowed; however,
intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not
allowed
• Patients with a history of life-threatening autoimmune disease or active autoimmune
disease that has required systemic treatment in the past 2 years (i.e. with use of
disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement
therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy
for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
treatment
• Patients with a history of non-infectious pneumonitis that required corticosteroid
treatment, or has current pneumonitis
• Patients with a history of allergic reactions to the tetanus vaccine
Open-label Study Comparing Iberdomide, Daratumumab and Dexamethasone (IberDd) Versus Daratumumab, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) (EXCALIBER-RRMM)
This is a multicenter, two-stage, randomized, controlled, open-label, Phase 3 study comparing
the efficacy and safety of iberdomide in combination with dexamethasone and daratumumab
(IberDd) versus daratumumab, bortezomib, and dexamethasone (DVd) in participants with
relapsed or refractory multiple myeloma (RRMM).
Timothy Schmidt, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04975997
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Inclusion Criteria
• Documented diagnosis of multiple myeloma (MM) and measurable disease.
• Received 1 to 2 prior lines of anti-myeloma therapy.
• Must have documented disease progression during or after their last anti-myeloma
regimen.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
Exclusion Criteria
• Any condition that confounds the ability to interpret data from the study.
• Has plasma cell leukemia, Waldenstrom's macroglobulinemia or POEMS syndrome
(polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes),
or clinically significant amyloidosis.
• Known central nervous system involvement with MM.
• Prior therapy with iberdomide.
• Other protocol-defined Inclusion/Exclusion criteria apply.
T-DM1 and Tucatinib Compared With T-DM1 Alone in Preventing Relapses in People With High Risk HER2-Positive Breast Cancer, the CompassHER2 RD Trial
This phase III trial studies how well trastuzumab emtansine (T-DM1) and tucatinib work in
preventing breast cancer from coming back (relapsing) in patients with high risk, HER2
positive breast cancer. T-DM1 is a monoclonal antibody, called trastuzumab, linked to a
chemotherapy drug, called DM1. Trastuzumab is a form of targeted therapy because it attaches
to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors,
and delivers DM1 to kill them. Tucatinib may stop the growth of tumor cells by blocking some
of the enzymes needed for cell growth. Giving T-DM1 and tucatinib may work better in
preventing breast cancer from relapsing in patients with HER2 positive breast cancer compared
to T-DM1 alone.
Kari Wisinski, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04457596
Show full eligibility criteria
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Inclusion Criteria:
• HER2-positive status will be based on pretreatment biopsy material and defined as an
immunohistochemistry (IHC) score of 3+ and/or positive by in situ hybridization (ISH)
according to current American Society of Clinical Oncology (ASCO) College of American
Pathologists (CAP) guidelines. Central testing is not required
* Known hormone receptor (HR) status as defined by ASCO/CAP guidelines (based on
pretreatment biopsy material). Hormone receptor positive status can be determined by
either known positive estrogen receptor (ER) or known positive progesterone receptor
(PR) status; hormone receptor negative status must be determined by both known
negative ER and known negative PR
• Patients with clinical stage T1-4, N0-3 disease at presentation and residual invasive
disease postoperatively as defined above are eligible. (Note: Patients with T1a/bN0
tumors are not eligible at initial breast cancer diagnosis are not eligible)
• Patients with residual HR-negative, HER2 positive (+) disease in the breast and/or
lymph nodes per the surgical pathology report are eligible; however, patients with HR+
HER2+ cancers must have node-positive residual disease per the surgical pathology
report in order to qualify for the study. The presence of residual invasive disease in
the breast is not mandatory for these patients
• Patients with weakly ER-positive (1-10%) breast cancer (based on the pretreatment core
biopsy) are eligible even if they have node-negative disease per the surgical
pathology report
• The residual disease tissue (breast and/or lymph nodes) is not required to be
HER2-positive, as eligibility for NCI-2020-03770 (A011801) is based on a positive HER2
status at the time of the initial breast cancer diagnosis
* Note: The presence of micrometastases in lymph nodes after preoperative therapy
counts as residual disease, whereas the presence of isolated tumor cells does not
• Patients with synchronous bilateral invasive disease are eligible provided both
lesions were confirmed to be HER2-positive, and at least one of the lesions meets the
criteria outlined above. Multifocal disease is allowed, as long as the largest
biopsied breast tumor was HER2-positive
• Patients must have received neoadjuvant chemotherapy with one of the following
regimens: docetaxel/trastuzumab/pertuzumab (THP), paclitaxel/methotrexate/cisplatin
(TMP), doxorubicin/cyclophosphamide/paclitaxel/trastuzumab/pertuzumab (AC-TH(P));
docetaxel/carboplatin/trastuzumab/pertuzumab (TCH(P));
fluorouracil/doxorubicin/cyclophosphamide-docetaxel/trastuzumab/pertuzumab
(FAC-TH(P)), or
fluorouracil/epirubicin/cyclophosphamide-docetaxel/trastuzumab/pertuzumab (FEC-TH(P)).
Note: apart from TCHP, where T is docetaxel, treatment with docetaxel or paclitaxel is
acceptable
• Prior receipt of T-DM1 in the neoadjuvant setting is not allowed.
• Prior treatment must have consisted of >= 6 cycles of chemotherapy and
HER2-directed therapy, with a total duration of >= 12 weeks, including at least 9
weeks of preoperative taxane and trastuzumab with or without pertuzumab (or Food
and Drug Administration [FDA]-approved biosimilars). Patients who have received
at least 9 weeks of preoperative taxane, pertuzumab and margetuximab are also
eligible if they received >= 6 cycles of systemic therapy prior to enrollment.
Note: Patients who complete at least nine of a planned twelve doses of weekly
paclitaxel, or three of a planned four doses of docetaxel, but discontinue
prematurely due to toxicity are eligible. Patients receiving dose-dense
chemotherapy regimens are also eligible. Prior use of nab-paclitaxel (Abraxane)
instead of paclitaxel or docetaxel is permitted. Prior use of subcutaneous
trastuzumab (Hylecta) and subcutaneous trastuzumab and pertuzumab (Phesgo) is
also allowed.
• Patients who received neoadjuvant systemic therapy which included experimental
HER2-targeted therapy/therapies are potentially eligible, as long as the
investigational agent was not a HER2-targeted antibody-drug conjugate (e.g.
T-DM1, DS-8201a [trastuzumab deruxtecan]) or a HER2 targeted tyrosine kinase
inhibitor (TKI) (e.g. tucatinib, lapatinib, neratinib).
• Patients may have received =< 1 cycles of T-DM1 in the adjuvant setting. Note: These
patients will be randomized to receive a further 14 cycles of T-DM1 and
tucatinib/placebo as tolerated. The most recent cycle of T-DM1 should have been
administered =< 5 weeks prior to registration
* Note: Both of the following two criteria need to be met for the patient to be
eligible for this study
• An interval of no more than 12 weeks between the completion date of the last
definitive treatment (e.g. postoperative chemotherapy or radiation, or if neither
given, breast surgical date) and the date of registration. Concurrent radiation
therapy is permitted while receiving study treatment
• Patients must be registered on study within =< 180 days of the date of the most
recent definitive breast cancer surgery (not including reconstructive surgery)
• All systemic chemotherapy should have been completed preoperatively unless
participating in EA1181 (CompassHER2 pathologic complete response [pCR]) or the BIG
DECRESCENDO Trial (which is very similar to CompassHER2 pCR in terms of study design,
drugs, and eligibility). However, patients who received 4 cycles of neoadjuvant THP
off study can receive a further 2-4 cycles of chemotherapy postoperatively to meet
eligibility for A011801. Patients who participated in EA1181 or MA41 and proceeded to
surgery immediately after the de-escalated trial regimen must receive postoperative
chemotherapy to complete a total of >= 6 cycles of systemic treatment prior to
enrollment on A011801, as outlined above (e.g. 4 cycles pre-operatively, and 2 cycles
post-operatively). The postoperative chemotherapy regimen prescribed is at the
discretion of the treating oncologist (i.e. 2-4 cycles AC or THP, other). Continuation
of trastuzumab + pertuzumab (HP) pre- or post-operatively as maintenance therapy
(while awaiting a surgical date or an official pathology report) is allowed for all
study participants
• Toxicities related to prior systemic treatment should have resolved or be at baseline,
apart from alopecia and peripheral neuropathy =< grade 1
• Adequate excision: surgical removal of all clinically evident disease in the breast
and lymph nodes as follows:
• Breast surgery: total mastectomy with no gross residual disease at the margin of
resection, or breast-conserving surgery with histologically negative margins of
excision
• For patients who undergo breast-conserving surgery, the margins of the resected
specimen must be histologically free of invasive tumor and ductal carcinoma in
situ (DCIS) as determined by the local pathologist. If pathologic examination
demonstrates tumor at the line of resection, additional operative procedures may
be performed to obtain clear margins. If tumor is still present at the resected
margin after re-excision(s), the patient must undergo total mastectomy to be
eligible. Patients with margins positive for classic lobular carcinoma in situ
(LCIS) are eligible without additional resection
• Lymph node surgery ** The axilla needs to be evaluated with either sentinel node
biopsy or axillary lymph node dissection. If patients have a sentinel lymph node
biopsy and sentinel nodes are negative, no further axillary treatment is
necessary. If patients have isolated tumor cells (ITCs) in the setting of
residual breast disease, at least one of the following is required: axillary
lymph node dissection (ALND) or planned nodal irradiation. If patients have
micro- or macro-metastatic nodal disease, ALND and planned nodal irradiation are
required. Of note, co-enrollment on Alliance A011202 is not allowed
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Absolute neutrophil count (ANC) >= 1,000/mm^3
• Hemoglobin >= 8 g/dL (Note: packed red blood cells [PRBC] transfusion is not permitted
to achieve eligibility)
• Platelet count >= 100,000/mm^3
• Creatinine =< 1.5 x upper limit of normal (ULN)
• Total bilirubin =< 1.0 x upper limit of normal (ULN) or direct bilirubin within the
institutional normal range for patients with Gilbert's syndrome
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit
of normal (ULN)
• Screening left ventricular ejection fraction (LVEF) >= 50% on echocardiogram (ECHO) or
multiple-gated acquisition (MUGA) after receiving neoadjuvant chemotherapy and no
decrease in LVEF by more than 15% absolute percentage points from the pre-chemotherapy
LVEF. Or, if pre-chemotherapy LVEF was not assessed, the screening LVEF must be >= 55%
after completion of neoadjuvant chemotherapy. Note: LVEF assessment may be repeated
once up to 3 weeks following the initial screening assessment to assess eligibility
Exclusion Criteria:
• No adjuvant treatment with any anti-cancer investigational drug within 28 days prior
to registration
• Not pregnant and not nursing, because this study involves an agent that has known
genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing
potential only, a negative serum pregnancy test done =< 7 days prior to registration
is required
• Patients with known active and/or untreated hepatitis B or hepatitis C or chronic
liver disease are ineligible. Patients with a diagnosis of hepatitis B or C that has
been treated and cleared and normal liver function are eligible to participate in the
study if the other eligibility parameters are met
• Stage IV (metastatic) breast cancer
• History of any prior (ipsi- or contralateral) invasive breast cancer within 3 years of
registration
• Patients with ER+ HER2+ residual invasive disease that is lymph node-negative per the
surgical pathology report
• Evidence of recurrent disease following preoperative therapy and surgery
• Patients for whom radiotherapy would be recommended for breast cancer treatment but
for whom it is contraindicated because of medical reasons (e.g., connective tissue
disorder or prior ipsilateral breast radiation)
• History of exposure to the following cumulative doses of anthracyclines: doxorubicin >
240 mg/m^2; epirubicin or liposomal doxorubicin-hydrochloride (Myocet) > 480 mg/m^2.
For other anthracyclines, exposure equivalent to doxorubicin > 240 mg/m^2
• Cardiopulmonary dysfunction as defined by any of the following:
• History of National Cancer Institute (NCI) CTCAE version (v) 5.0 grade >= 3
symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA)
criteria class >= II
• Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not
controlled by adequate medication, severe conduction abnormality, or clinically
significant valvular disease
• High-risk uncontrolled arrhythmias: i.e., atrial tachycardia with a heart rate >
100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or
higher-grade atrioventricular block (AV)-block (second degree AV-block type 2
[Mobitz 2] or third degree AV-block)
• Significant symptoms (grade >= 2) relating to left ventricular dysfunction,
cardiac arrhythmia, or cardiac ischemia while or since receiving preoperative
therapy
• History of a decrease in left ventricular ejection fraction (LVEF) to < 40% with
prior trastuzumab treatment (e.g., during preoperative therapy)
• Uncontrolled hypertension (systolic blood pressure > 180 mmHg and/or diastolic
blood pressure > 100 mmHg)
• Current severe, uncontrolled systemic disease
• Major surgical procedure unrelated to breast cancer or significant traumatic injury
within 28 days prior to registration or anticipation of the need for major surgery
during the course of study treatment
• History of intolerance, including grade 3 to 4 infusion reaction or hypersensitivity
to trastuzumab or murine proteins or any components of the product
• Peripheral neuropathy of any etiology that exceeds grade 1
• Assessment by the investigator as being unable or unwilling to comply with the
requirements of the protocol
• Use of a strong CYP3A4 or CYP2C8 inhibitor within 2 weeks, or use of a strong CYP3A4
or CYP2C8 inducer within 5 days prior to registration is prohibited.
• Please note that use of sensitive CYP3A substrates should be avoided two weeks
before registration and during study treatment. Additionally, CYP3A4 or CYP2C8
inducers are prohibited as concomitant medications within 5 days following
discontinuation of tucatinib treatment. Patients who require medications that are
known to be sensitive substrates of CYP3A4 with a narrow therapeutic window
should be excluded.
Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Anatomic Stage IIB Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, HER2 Positive Breast Carcinoma, Invasive Breast Carcinoma, Multifocal Breast Carcinoma, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage IA Breast Cancer AJCC v8, Prognostic Stage IB Breast Cancer AJCC v8, Prognostic Stage II Breast Cancer AJCC v8, Prognostic Stage IIA Breast Cancer AJCC v8, Prognostic Stage IIB Breast Cancer AJCC v8, Prognostic Stage III Breast Cancer AJCC v8, Prognostic Stage IIIA Breast Cancer AJCC v8, Prognostic Stage IIIB Breast Cancer AJCC v8, Prognostic Stage IIIC Breast Cancer AJCC v8, Synchronous Bilateral Breast Carcinoma, Breast
Impact of DNA Repair Pathway Alterations on Sensitivity to Radium-223 in Bone Metastatic Castration-resistant Prostate Cancer
This study investigates how well radium-223 works in treating patients with
castration-resistant prostate cancer than has spread to the bones (bone metastases). Prostate
cancer is the most common cancer in men and the second leading cause of cancer death.
Furthermore, many men with notably advanced disease have been found to have abnormalities in
DNA repair. The purpose of this research is to study the role of a DNA repair pathway in
prostate cancer, specifically in response to administration of radium-223, an FDA-approved
drug known to cause DNA damage to cancerous cells. Understanding how defects in the DNA
repair pathway affects radium-223 treatment of prostate, may help doctors help plan effective
treatment in future patients.
Glenn Liu, MD
Male
18 Years and over
II
This study is NOT accepting healthy volunteers
NCT04489719
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Inclusion Criteria:
• Patient must be >= 18 years of age
• Patient must have histopathologic diagnosis of prostate cancer
• Patient must have castration-resistant prostate cancer
• Patient must have radiographic evidence of bone metastasis
• Patients must be symptomatic from prostate cancer
• Patient must have plans to undergo treatment with radium-223
• Patient must have a PSA level >= 10 ng/mL
• Patient must have castrate testosterone levels demonstrated within the last 3 months
prior to screening
• Patient must have anticipated survival > 3 months
• Patient must be willing and able to authorize consent
• Patient must be willing and able to comply with the protocol, including follow-up
visits
Exclusion Criteria:
• Patient must not have visceral metastasis
• Patients on regimens of radium-223 in combination with other antineoplastic agents are
excluded
* Bone-targeted only therapy (e.g. denosumab or zoledronic acid) will be allowed
• Patients who have received prior radium-223
• Patients who have received prior platinum containing chemotherapy
• Absolute neutrophil count (ANC) < 1.5 x 10^9/L
• Hemoglobin (HB) < 9 g/dL
• Platelets (PLT) < 100 x 10^9/L
• Any condition which, in the investigator's opinion, makes the subject unsuitable for
trial participation
Castration-Resistant Prostate Carcinoma, Metastatic Malignant Neoplasm in the Bone, Metastatic Prostate Carcinoma, Stage IV Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8, Prostate
APOLLO: A Randomized Phase II Double-Blind Study of Olaparib Versus Placebo Following Curative Intent Therapy in Patients With Resected Pancreatic Cancer and a Pathogenic BRCA1, BRCA2 or PALB2 Mutation
This phase II trial investigates how well the addition of olaparib following completion of
surgery and chemotherapy works in treating patients with pancreatic cancer that has been
surgically removed (resected) and has a pathogenic mutation in BRCA1, BRCA2, or PALB2.
Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA)
when it becomes damaged. Blocking PARP may help keep tumor cells from repairing their damaged
DNA, causing them to die. PARP inhibitors are a type of targeted therapy.
Monica Patel
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04858334
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Inclusion Criteria:
• STEP 0 (PRE-REGISTRATION) INCLUSION CRITERIA
• Patient must be >= 18 years of age on day of consent
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0-2
• Patient must have a diagnosis of pancreatic cancer and have successfully undergone a
curative intent surgical resection and must have no evidence of recurrent disease as
determined by the investigator
• NOTE: This includes patients with adenocarcinoma, acinar carcinoma, squamous cell
carcinoma adenosquamous and variants thereof. Patients with neuroendocrine tumors
are excluded from enrolling
• Patient must (1) be planning to receive, (2) be receiving or (3) have received at
least three combined months (i.e., 12 weeks) of perioperative (neoadjuvant, adjuvant
or a combination of both) systemic, multi-agent chemotherapy. Patients may have had up
to 6 months of perioperative systemic therapy as deemed appropriate by their primary
treating medical team (patients can have received radiation or chemoradiation in
addition to this 6 month course)
• Patient must be no more than 12 weeks from their most recent treatment (this may be
chemotherapy, radiotherapy or surgery)
• Patient must have a known pathogenic or likely pathogenic germline or somatic mutation
in BRCA1, BRCA2, or PALB2, as determined by a Clinical Laboratory Improvement
Amendments (CLIA) certified or equivalently-accredited laboratory. Mutations must be
considered pathogenic or likely pathogenic by a reference database such as ClinVar or
OncoKb.org
• STEP 1 (RANDOMIZATION) INCLUSION CRITERIA
• Patient must have met the eligibility criteria outlined above
• Patient must have undergone at least 3 combined months (i.e., 12 weeks) of
perioperative (neoadjuvant, adjuvant or a combination of both) systemic, multi-agent
chemotherapy. Patients may have had up to 6 months of perioperative systemic therapy
as deemed appropriate by their primary treating medical team (patients can have
received radiation or chemoradiation in addition to this 6 months course)
• Central expert reviewer must have determined the patient eligible for randomization
after review of local genetic testing reports
• If mutation in BRCA1, BRCA2 or PALB2 was identified in tumor tissue and the patient
has not previously undergone germline testing, the patient must agree to undergo
germline testing
• Patient must have no evidence of recurrent or metastatic pancreatic cancer at the time
of randomization as documented by baseline scans obtained =< 4 weeks prior to Step 1
randomization
• Patient must not have previously had evidence of progressive pancreatic cancer while
receiving platinum-based therapy
• Patient must be >= 21 days (three weeks) from their last treatment (including
chemotherapy radiotherapy or surgery) but =< 84 days (twelve weeks) from their last
treatment at the time of Step 1 randomization. Patients who have received neoadjuvant
and/or adjuvant radiotherapy are eligible
• Patient must have recovered from any adverse events due to prior anti-cancer therapy
(i.e., have no residual toxicities > grade 1 with the exception of alopecia and/or
neuropathy)
• Patient must not be receiving any other investigational agents at the time of Step 1
randomization and while on protocol treatment
• Patient must not have any history of allergic reactions attributed to compounds of
similar chemical or biological composition to olaparib
• Patient must not have any personal history of myelodysplastic syndrome (MDS) or acute
myeloid leukemia (AML). Patients with myelodysplastic syndrome/acute myeloid leukemia
or with features suggestive of MDS/AML.
• Patient must not have any uncontrolled gastrointestinal disorder that would, in the
opinion of the investigator, interfere with the ingestion or absorption of olaparib
• Patient must not be pregnant or breast-feeding due the potential harm to an unborn
fetus and possible risk for adverse events in nursing infants with the treatment
regimens being used. All patients of childbearing potential must have a blood test or
urine study within 14 days prior to Step 1 randomization to rule out pregnancy. A
patient of childbearing potential is defined as anyone, regardless of sexual
orientation or whether they have undergone tubal ligation, who meets the following
criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy
or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea
following cancer therapy does not rule out childbearing potential) for at least 24
consecutive months (i.e., has had menses at any time in the preceding 24 consecutive
months)
• Patients must not expect to conceive or father children by using accepted and
effective method(s) of contraception or by abstaining from sexual intercourse for the
duration of their participation in the study and for 6 months after the last dose of
protocol treatment for female patients and for 3 months after the last dose of
protocol treatment for male patients. Patients must also not donate sperm while on
protocol treatment and for 3 months after the last dose of protocol treatment.
Patients must also not breast-feed while on protocol treatment and for 1 month after
the last dose of protocol treatment
• Leukocytes >= 3,000/mcL (obtained =< 28 days prior to Step 1 randomization)
• Absolute neutrophil count >= 1,500/mcL (obtained =< 28 days prior to Step 1
randomization)
• Platelets >= 100,000/mcL (obtained =< 28 days prior to Step 1 randomization)
• Hemoglobin >= 9.0 g/dL with no blood transfusion in the past 28 days (obtained =< 28
days prior to Step 1 randomization)
• Total bilirubin =< 1.5 institutional upper limit of normal (ULN) except in patients
with Gilbert's syndrome. Patients with Gilbert's syndrome may enroll if direct
bilirubin =< 2.5 x ULN of the direct bilirubin (obtained =< 28 days prior to Step 1
randomization)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 institutional ULN (obtained =< 28 days prior to Step 1 randomization)
• Creatinine =< 1.5 institutional ULN OR calculated Cockcroft Gault creatinine clearance
> 50 mL/min/1.73 m^2 (obtained =< 28 days prior to Step 1 randomization)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
• Patient must not have resting electrocardiogram (ECG) indicating uncontrolled,
potentially reversible cardiac conditions, as judged by the investigator (e.g.
unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure,
corrected QT [QTc] prolongation > 500 ms, electrolyte disturbances, etc.) or have
congenital long QT syndrome
• Concomitant use of known potent CYP3A4/5 inhibitors such as ketoconazole,
itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and
nelfinavir is prohibited
• Patients who are being actively treated for an ongoing concurrent malignancy are
ineligible, with the exception of those receiving adjuvant hormone therapies and those
receiving topical therapies for skin cancers
• Patient must not have, in the opinion of the investigator, any other concurrent
medical condition that would prevent the patient from complying with the study
procedures
• Patient must not be considered a poor medical risk due to a serious, uncontrolled
medical disorder, non-malignant systemic disease or active, uncontrolled infection.
Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent
(within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable
spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral
lung disease on high resolution computed tomography (HRCT) scan or any psychiatric
disorder that prohibits obtaining informed consent
• Patient must have the ability to understand and the willingness to sign a written
informed consent document, or have legally authorized representative provide
authorization to participate
• Patient must not have had major surgery within 2 weeks prior to Step 1 randomization
and patients must have recovered from any effects of any major surgery
A Study of ARV-766 Given by Mouth in Men With Metastatic Prostate Cancer
A Phase 1/2 study to evaluate the safety and efficacy of ARV-766 given by mouth alone or in
combination with abiraterone in men with metastatic prostate cancer.
Joshua Lang, Post Grad
Male
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05067140
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Inclusion Criteria:
Part A,B,C and D:
• Histological, pathological, or cytological confirmed diagnosis of adenocarcinoma of
the prostate.
• Ongoing androgen deprivation therapy (ADT) with a gonadotropin releasing hormone
analog or inhibitor, or orchiectomy (surgical or medical castration).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Part A:
• Progression on at least 2 prior approved systemic therapies for metastatic prostate
cancer (at least one must be a second-generation androgen inhibitor, e.g.,
abiraterone, enzalutamide, darolutamide, apalutamide).
• Progressive mCRPC
Part B:
• Participants must have received at least one but no more than three prior second
generation anti-androgen agents (e.g., enzalutamide or abiraterone).
• Participants must have received no more than two prior chemotherapy regimens.
• Progressive mCRPC
Part C & D:
• Metastatic castration resistant or sensitive prostate cancer with radiographic evidence
of metastatic disease
Exclusion Criteria:
Part A and B:
• Known symptomatic brain metastases requiring steroids (above physiologic replacement
doses).
• Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular
disease, or previous gastric resection or lap band surgery.
• Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to
>25% of the bone marrow.
• Receipt of an investigational drug(s) within 4 weeks prior to anticipated first dose
• Systemic anti-cancer therapy within 2 weeks of first dose of study drug (except agents
to maintain castrate status). For bicalutamide, mitomycin C, or nitrosoureas the
exclusion period must be 6 weeks and for abiraterone 4 weeks.
Part C and D
• Prior treatment with a second generation NHA
Hypofractionated vs Conventional Fractionated RT in Soft Tissue Sarcomas
This research study is designed to find out if radiation therapy treatment prior to surgery
is safe and effective to treat soft tissue sarcomas. 30 participants with soft tissue sarcoma
will be enrolled and can expect to be on study for up to 5 years.
Zachary Morris, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05109494
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Inclusion Criteria:
• Biopsy proven soft tissue sarcoma of the extremity, trunk, or head and neck
• No prior sarcoma-directed therapy
• Age ≥ 18 years
• Karnofsky performance status ≥ 60
• Able to understand and sign an informed consent
• Life expectancy of greater than 12 weeks
• Hypofractionated or conventionally fractionated radiotherapy using Intensity Modulated
Radiation Therapy (IMRT) are both deemed feasible and safe neoadjuvant treatments, at
the treating physician's discretion
• Operable disease and medically fit for surgery, based on the opinion of the consulting
surgeon; surgery within 5-14 days of completion of radiation therapy (RT)
• Adequate bone marrow function as defined by absolute neutrophil count > 500/mcL,
hemoglobin > 8 g/dL, platelets > 50,000/mcL; adequate renal function as defined by
creatinine clearance > 30 mL/min
Exclusion Criteria:
• Pregnant
• Unable to undergo imaging or positioning necessary for radiotherapy planning
EPI-7386 in Combination With Enzalutamide Compared With Enzalutamide Alone in Subjects With mCRPC
This is a Phase 1/2 study of EPI-7386 orally administered in combination with enzalutamide in
subjects with mCRPC.
Phase 1 of the study will be a single-arm dose escalation study of EPI-7386 in combination
with a fixed dose of enzalutamide. This portion of the study will primarily evaluate the
safety and tolerability of the drug combination and establish the RP2CDs for EPI-7386 and
enzalutamide when dosed in combination. In addition, blood sampling will be conducted for PK
evaluation to assess the potential DDI between the two drugs.
Once the RP2CD for each drug has been established, Phase 2 of the study will commence. Phase
2 is a two-arm, randomized (2:1), open-label study. Approximately 120 subjects will be
randomized 2:1 to:
- Group 1: EPI-7386 at the RP2CD + enzalutamide(depending on the results of the Phase 1)
(n=80)
- Group 2: Enzalutamide single agent (n=40) The planned dose of enzalutamide and EPI-7386
for the combination arm will be those determined in the Phase 1 of this study based on
safety and exposure data. Subjects may remain on study treatment as long as they are
tolerating treatment without disease progression based on RECIST v1.1 and/or PCWG3.
Christos Kyriakopoulos, MD
Male
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05075577
Show full eligibility criteria
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Inclusion Criteria:
• Males ≥18 years.
• Histologically, pathologically, or cytologically confirmed prostate adenocarcinoma.
• Evidence of castration-resistant prostate cancer (CRPC).
• Presence of metastatic disease at study entry documented by 1 or more bone lesions on
bone scan or by soft tissue disease observed by CT/MRI.
• Naïve to second generation anti-androgens.
• Evidence of progressive disease defined as 1 or more Prostate Cancer Working Group 3
(PCWG3) criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Ongoing ADT with luteinizing hormone-releasing hormone (LHRH) agonist/antagonist
therapy or history of bilateral orchiectomy, with castrate level testosterone.
• Serum testosterone ≤1.73 nmol/L (50 ng/dL).
• Subjects receiving bisphosphonates or other approved bone-targeting therapy (e.g.,
denosumab) must be on a stable dose for at least 28 days prior to the start of study
treatment.
• Demonstrate adequate organ function.
Exclusion Criteria:
• Biologic anti-cancer therapy within 28 days prior to the start of study treatment.
• Use of hormonal agents with anti-tumor activity against prostate cancer within 28 days
prior to the start of study treatment.
• Use of herbal products or alternative therapies that may decrease PSA levels or that
may have hormonal anti-prostate cancer activity within 28 days prior to the start of
study treatment or plans to initiate during the study.
• Intervention with any chemotherapy, investigational agents, or other anti-cancer drugs
within 28 days of the first dose of study treatment.
• Use of radium-223 dichloride or other radioligand/radiopharmaceutical within 28 days
prior to the start of study treatment.
• Received limited-field palliative bone radiotherapy >5 fractions and/or any
radiotherapy within 2 weeks prior to the start of study treatment.
• Received a blood transfusion within 28 days of hematologic screening labs.
• Known intra-cerebral disease or brain metastasis unless adequately treated and stable
for the last 28 days before signing of informed consent.
• Spinal cord compression.
• Diagnosis of another clinically significant malignancy within the previous 3 years
other than curatively treated non-melanomatous skin cancer or superficial urothelial
carcinoma and other in situ or non-invasive malignancies.
• Gastrointestinal issues affecting absorption.
• Significant cardiovascular disease.
• Known history of seizure or conditions that may pre-dispose them to seizure, including
brain injury with loss of consciousness, transient ischemic attack within the past 12
months, cerebral vascular accident, brain metastases, and brain arteriovenous
malformation.
• Concurrent disease or any clinically significant abnormality.
• Known or suspected hypersensitivity to any components of the formulation used for
EPI-7386 or enzalutamide.
• Use of strong inhibitors of CYP2C8.
• Use of strong inducers of CYP3A.
• Use of narrow therapeutic index sensitive CYP2C8 or sensitive substrates for CYP3A and
CYP2B6.
• Use of granulocyte colony stimulating factor within 7 days prior to screening
laboratories.
• Not a candidate for enzalutamide treatment.
• Patients with rare hereditary problems of fructose intolerance.
Testing the Addition of the Anti-cancer Drug, Tazemetostat, to the Usual Treatment (Dabrafenib and Trametinib) for Metastatic Melanoma That Has Progressed on the Usual Treatment
This phase I/II trial investigates the best dose, possible benefits and/or side effects of
tazemetostat in combination with dabrafenib and trametinib in treating patients with melanoma
that has a specific mutation in the BRAF gene (BRAFV600) and that has spread to other places
in the body (metastatic). Tazemetostat, dabrafenib, and trametinib may stop the growth of
tumor cells by blocking some of the enzymes needed for cell growth. Giving tazemetostat in
combination with dabrafenib and trametinib may stabilize BRAFV600 mutated melanoma.
Mark Albertini, M.D.
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04557956
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Inclusion Criteria:
• Patient must have a diagnosis of BRAF^V600E/K-mutated metastatic melanoma
• Patient must have had documented radiographic or clinical evidence of progressive
disease while on combination BRAF/MEK inhibitor therapy. For Phase 2 only, no more
than one intervening therapy since progression on BRAF/MEK inhibitor therapy is
allowed. Subjects who have evidence of progression while on, or within 4 weeks of
completing, combination BRAF/MEK inhibitor therapy in the adjuvant setting will be
eligible
• PHASE 2 ONLY: Patient must have EZH2 alteration (somatic mutation or copy number
alteration). Can be performed on either archival or fresh specimen. EZH2 alterations
need to be documented by a Clinical Laboratory Improvement Act (CLIA)/Clinical
Laboratory Improvement Program (CLIP)-certified next generation sequencing platform
(Foundation One, Tempus, Guardant360, etc.)
• PHASE 2 ONLY: Patient must have measurable disease
• PHASE 2 ONLY: Patient must have at least one tumor lesion amenable to biopsy. If
possible, this lesion should be different from the lesion used for following tumor
measurements but is not required
• PHASE 2 ONLY: Patient must agree to planned pre-treatment and planned on-treatment
biopsy. A pre-treatment biopsy will be optional if patient has an archival tissue
block or 5 formalin-fixed paraffin-embedded (FFPE) slides available from specimen used
to document presence of eligible EZH2 alteration that is deemed adequate for
evaluation
• Patient must be >=18 years
• Because no dosing or adverse event data are currently available on the use of
tazemetostat in combination with dabrafenib and trametinib in patients < 18 years
of age, children are excluded from this study
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
(Karnofsky >= 50%)
• Patients with symptomatic central nervous system (CNS) metastases are eligible if
previously treated with surgery and/or radiation with no evidence of radiologic CNS
recurrence or progression for 4 weeks and on a stable/tapering dose of steroid for at
least one week prior to start of study drug. Patients with new or progressive
asymptomatic CNS metastases are eligible
• Hemoglobin >= 9 g/dL
• Albumin >= 2.5 g/dL
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN) except subjects
with known Gilbert's syndrome
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x institutional ULN
• Creatinine =< 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault formula)
>= 50 mL/min
• Glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2
• Patients with a prior (or concurrent, if enrolling in Phase 1) malignancy whose
natural history or treatment does not have the potential to interfere with the safety
or efficacy assessment of the investigational regimen are eligible for this trial
• Patient must be able to swallow and retain oral medication and must not have any
clinically significant gastrointestinal abnormalities that may alter absorption such
as malabsorption syndrome or major resection of the stomach or bowels
• Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin
time (PTT) =< 1.3 x institutional ULN. Prophylactic low dose warfarin may be given to
maintain central catheter patency
• The effects of tazemetostat, and the combination of tazemetostat, dabrafenib and
trametinib on the developing human fetus are unknown. Women of childbearing potential
and all male patients must agree to the following:
• For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods that result in a failure
rate of < 1% per year during the treatment period, for 6 months after
tazemetostat discontinuation, or for 6 months after discontinuation of the
combination of tazemetostat, dabrafenib and trametinib. Should a woman become
pregnant or suspect she is pregnant while she is participating in this study, she
should inform her treating physician immediately
• A woman is considered to be of childbearing potential if she is
postmenarcheal, has not reached a postmenopausal state (>= 12 continuous
months of amenorrhea with no identified cause other than menopause), and has
not undergone surgical sterilization (removal of ovaries and/or uterus)
• Examples of contraceptive methods with a failure rate of < 1% per year
include bilateral tubal ligation, male sterilization, established, proper
use of hormonal contraceptives that inhibit ovulation, hormone-releasing
intrauterine devices, and copper intrauterine devices
• Due to the potential of enzyme induction with tazemetostat, female subjects
who use hormonal contraceptives should use an additional barrier method of
birth control while on study treatment and for 6 months after
discontinuation of tazemetostat or the combination of tazemetostat,
dabrafenib and trametinib
• The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical study and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
post ovulation methods) and withdrawal are not acceptable methods of
contraception
• Women of childbearing potential must have a negative urine or serum pregnancy
test at screening
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or
use contraceptive measures and agreement to refrain from donating sperm, as
defined below:
• With female partners of childbearing potential or pregnant female partners,
men must remain abstinent or use a condom during the treatment period and
for at least 4 months after the last dose of study drug. Men must refrain
from donating sperm during this same period. In addition, female partners of
male subjects should adhere to the following:
• Intrauterine device (IUD) (must provide medical documentation of IUD)
• Hormonal contraceptive (partner must be on a stable dose of the same
hormonal contraceptive product for at least 4 weeks before receiving
study drug) AND a condom (hormonal contraceptives must be supplemented
with condoms)
• The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical study and the preferred and usual lifestyle of the
patient. Periodic abstinence and withdrawal are not acceptable methods of
contraception
• Ability to understand and the willingness to sign a written informed consent document.
Participants with impaired decision-making capacity (IDMC) who have a
legally-authorized representative (LAR) and/or family member available will also be
eligible
• Have progressed on, been intolerant to is, ineligible for, or has refused prior
standard of care anti-PD-1 based immunotherapy
Exclusion Criteria:
• Previous therapy with a demethylating agent (i.e. decitabine) or previous therapy with
an EZH2 inhibitor
• History of second malignancy not treated with curative intent
• History of life-threatening toxicity, including hypersensitivity, related to BRAF or
MEK inhibitor therapy, or known immediate or delayed hypersensitivity reaction or
idiosyncrasy to drugs chemically related to the study treatments, their excipients,
and/or dimethyl sulfoxide (DMSO)
• Active infection requiring intravenous therapy
• Presence of untreated or progressive symptomatic CNS melanoma metastases. Diffuse
leptomeningeal carcinomatosis or metastases causing spinal cord compression are
exclusionary. Previously treated lesions should be stable for >= 4 weeks (must be
documented by imaging). Subjects on a stable dose of corticosteroids for > 1 week can
be enrolled. Subjects must also be off of enzyme-inducing anticonvulsants for > 4
weeks
• Radiation therapy in the last 14 days. Palliative radiation to a localized area
without residual toxicity requires a washout of at least 7 days
• Prior systemic anti-cancer therapy (chemotherapy, targeted therapy, immunotherapy,
biologic therapy, or vaccine therapy) within the 3 weeks preceding the first dose of
study treatment. For Phase 2 only, prior chemotherapy regimens are not permitted
• Use of other investigational drugs within 28 days (or five half-lives, whichever is
shorter; with a minimum of 14 days from the last dose) preceding the first dose of
study treatment and during the study
• Unresolved toxicity of National Cancer Institute Common Terminology Criteria for
Adverse Events, version 5.0 (NCI CTCAE v5.0) grade 2 or higher from previous
anti-cancer therapy, except alopecia, at the time of randomization
• Current use of a prohibited medication. Patients must not be treated with any
medications or substances that are strong or moderate inhibitors or inducers of of
CYP3A or strong inhibitors or inducers of CYP2C8 within 14 days prior to the first
treatment through the end of the study. Current use of, or intended ongoing treatment
with: herbal remedies (e.g., St. John's wort), or strong inhibitors or inducers of
P-glycoprotein (Pgp) or breast cancer resistance protein 1 (Bcrp1) should also be
excluded
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are ineligible because of the potential for pharmacokinetic interactions with
dabrafenib
• A history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (with the
exception of cleared HBV and HCV infection, which will be allowed)
• History of interstitial lung disease or pneumonitis
• Clinically significant bleeding diathesis or coagulopathy, including known platelet
function disorders. Patients on anticoagulation with low molecular weight heparin or
low dose warfarin are allowed
• History of myeloid malignancies, including myelodysplastic syndrome (MDS)
• Has abnormalities known to be associated with MDS (e.g. del 5q, chr 7 abn) and
multiple primary neoplasms (MPN) (e.g. JAK2 V617F) observed in cytogenetic testing and
deoxyribonucleic acid (DNA) sequencing
• History of T-lymphoblastic lymphoma (T-LBL)/T-cell acute lymphoblastic leukemia
(T-ALL)
• Patients with history of RAS mutation-positive tumors are not eligible regardless of
interval from the current study. Note: Prospective RAS testing is not required.
However, if the results of previous RAS testing are known, they must be used in
assessing eligibility
• History or evidence of cardiovascular risks including any of the following:
• QT interval corrected for heart rate using Fridericia's formula (QT corrected by
Fridericia [QTcF]) >= 450 msec
• History of acute coronary syndromes (including myocardial infarction or unstable
angina), coronary angioplasty, or stenting within the past 24 weeks prior to
randomization
• History or evidence of current class II, III, or IV heart failure as defined by
the New York Heart Association (NYHA) functional classification system
• Intra-cardiac defibrillators
• Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram
(ECHO); (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis]
can be entered on study). Subjects with moderate valvular thickening should not
be entered on study
• History or evidence of current clinically significant uncontrolled cardiac
arrhythmias; clarification: Subjects with atrial fibrillation controlled for > 30
days prior to dosing are eligible
• Treatment refractory hypertension defined as a blood pressure of systolic > 140
mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive
therapy
• Left ventricular ejection fraction (LVEF) < institutional lower limit of normal
(LLN) by ECHO or multigated acquisition scan (MUGA)
• Known cardiac metastases
• Patients with uncontrolled intercurrent illness
• Patients with psychiatric illness/social situations that would limit compliance with
study requirements
• Pregnant women are excluded from this study because of the potential for teratogenic
or abortifacient effects. Because there is an unknown but potential risk for adverse
events in nursing infants secondary to treatment of the mother with tazemetostat /
dabrafenib / trametinib, breastfeeding should be discontinued prior to treatment
• Patients with uncontrolled diabetes
• Patients with a history of retinal vein occlusion (RVO), retinal pigment epithelial
detachment (RPED) or other ophthalmologic toxicity
Clinical Stage IV Cutaneous Melanoma AJCC v8, Metastatic Melanoma, Melanoma, Skin, Melanoma/Skin cancer
Study to Assess Change in Disease Activity and Adverse Events of Oral Venetoclax With Intravenous (IV) Obinutuzumab in Adult Participants With Recurring Chronic Lymphocytic Leukemia (CLL) (ReVenG)
Chronic lymphocytic leukemia (CLL) is the most common leukemia (cancer of blood cells). The
purpose of this study is to assess retreatment with venetoclax-obinutuzumab (VenG) in
participants previously treated with fixed duration first-line (IL) therapy of venetoclax in
combination with an anti-CD20 antibody +/- X (where X is any additional drug). Adverse events
and change in disease activity will be assessed.
Venetoclax is an approved drug for the treatment of CLL. Study doctors put the participants
in 1 of 2 groups, called cohorts, based on when symptoms of CLL came back after previous
treatment in first-line. Approximately 75 adult participants with CLL who have been treated
with venetoclax in combination with an anti-CD20 antibody +/- X will be enrolled in the study
in approximately 60 sites worldwide.
Participants will receive intravenous (IV) obinutuzumab + oral venetoclax (VenG) in 28-day
cycles for a total of 6 cycles per cohort, followed by 6 to 18 cycles of venetoclax alone,
for a total treatment of 12 to 24 cycles, depending on the cohort.
There may be higher treatment burden for participants in this trial compared to their
standard of care. Participants will attend regular visits during the study at a hospital or
clinic. The effect of the treatment will be checked by medical assessments, blood tests,
checking for side effects and completing questionnaires.
Christopher Fletcher, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04895436
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Inclusion Criteria:
• Documented diagnosis of chronic lymphocytic leukemia (CLL) that requires treatment for
CLL according to International Workshop for Chronic Lymphocytic Leukemia (iwCLL) 2018
criteria.
• Previously completed venetoclax + anti-CD20 antibody +/- X regimen as a fixed duration
first-line (1L) therapy and achieved documented response, defined as complete
remission, complete remission with incomplete marrow recovery, partial remission, or
nodular partial remission.
• More than 24 months (Cohort 1) or 12-24 months (Cohort 2) have elapsed between last
dose of venetoclax and disease progression after completion of 1L treatment.
Exclusion Criteria:
•Received intervening treatment for CLL after completing previous treatment with a
venetoclax + anti-CD20 antibody +/- X regimen.
Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C)
The purpose of this study is to find out whether the study drug, LY3537982, is safe and
effective in cancer patients who have a specific genetic mutation (KRAS G12C). Patients must
have already received or were not able to tolerate the standard of care, except for specific
groups who have not had cancer treatment. The study will last up to approximately 4 years.
Dustin Deming, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04956640
Show full eligibility criteria
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Inclusion Criteria:
• Patients have measurable disease per Response Evaluation Criteria in Solid Tumors
version 1.1 (RECIST v1.1).
• Patients must have disease with evidence of KRAS G12C mutation in tumor tissue or
circulating tumor deoxyribonucleic acid (DNA).
• Participants must have a histological or a cytologically proven diagnosis of locally
advanced, unresectable, and/or metastatic cancer and meet cohort-specific criteria.
• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Have adequate organ function.
• Have discontinued all previous treatments for cancer with resolution of any
significant ongoing adverse events (AEs), (except in certain scenarios).
• Must be able to swallow capsule/tablet.
• Agree and adhere to contraceptive use, if applicable.
• For some parts of the study, (i.e., one of the two arms with LY3537982 in combination
with pembrolizumab and the arm of LY3537982 in combination with pembrolizumab,
pemetrexed, and platinum therapy) histologically or cytologically confirmed Stage
IIIB-IIIC or Stage IV NSCLC that is previously untreated in the advanced/metastatic
setting and not suitable for curative intent radical surgery or radiation therapy.
Previously untreated patients who received adjuvant and neoadjuvant therapy are
eligible if the last dose of the systemic treatment was completed at least 6 months
prior to enrollment. For untreated patients in the arm with LY3537982 in combination
with pembrolizumab noted above, a single cycle of pembrolizumab may be initiated
within 21 days prior to enrollment. For untreated patients in the arm of LY3537982 in
combination with pembrolizumab, pemetrexed, and platinum therapy, a single cycle of
any or all of the drugs other than LY3537982 may be initiated within 21 days prior to
enrollment. Start of study treatment may be delayed to allow sufficient time for
recovery from treatment-related toxicity.
• For one part of the study, participants must have received at least one prior
oxaliplatin- or irinotecan-containing regimen for advanced or metastatic CRC.
Exclusion Criteria:
• Disease suitable for local therapy administered with curative intent.
• Have an active, ongoing, or untreated infection.
• Have a serious pre-existing medical condition(s) that, in the judgment of the
investigator, would preclude participation in this study.
• Have a serious cardiac condition.
• Have a second active primary malignancy or have been diagnosed and/or treated for an
additional malignancy within 3 years prior to enrollment.
• Have symptomatic central nervous system (CNS) malignancy or metastasis and/or
carcinomatous meningitis. Patients with treated CNS metastases are eligible for this
study if their disease is asymptomatic, radiographically stable for at least 30 days,
and they do not require treatment with steroids in the two-week period prior to study
treatment. This only applies to some parts of the study.
• Have received prior treatment with any KRAS G12C small molecule inhibitor, except in
certain scenarios where such prior therapy is allowed as per protocol.
• The following patients will be excluded from some parts of the study:
• Experienced certain serious side effects with prior immunotherapy.
• Have an active autoimmune disease that has required systemic anti-autoimmune
treatment in the past 2 years.
• Have received a live vaccine within 30 days prior to the first dose of study
drug.
• Pregnant, breastfeeding, or expecting to conceive or father children within the
projected duration of the trial through 180 days after the last dose of study
medication.
• Known allergic reaction against any of the components of the study treatments.
Lip, Oral Cavity and Pharynx, Esophagus, Colon, Anus, Liver, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Melanoma, Skin, Kaposi's Sarcoma, Breast, Cervix, Corpus Uteri, Other Female Genital, Other Male Genital, Kidney, Eye and Orbit, Brain and Nervous System, Other Endocrine System, Ill-Defined Sites, Anal, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Ovary, Sarcoma, Uterus, Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Endometrial Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Biliary Tract Neoplasms
Comparing High-Dose Cisplatin Every Three Weeks to Low-Dose Cisplatin Weekly When Combined With Radiation for Patients With Advanced Head and Neck Cancer
This phase II/III trial compares the effect of the combination of high-dose cisplatin every
three weeks and radiation therapy versus low-dose cisplatin weekly and radiation therapy for
the treatment of patients with locoregionally advanced head and neck cancer. Chemotherapy
drugs, such as cisplatin, work in different ways to stop the growth of tumor cells, either by
killing the cells, by stopping them from dividing, or by stopping them from spreading.
Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. This study
is being done to find out if low-dose cisplatin given weekly together with radiation therapy
is the same or better than high-dose cisplatin given every 3 weeks together with radiation
therapy in treating patients with head and neck cancer.
Paul Harari, MD
All
18 Years and over
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT05050162
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Inclusion Criteria:
• Pathologically (histologically or cytologically) proven diagnosis of SCCHN of the
oropharynx, larynx, hypopharynx, or p16-positive unknown primary prior to
registration; specimen from cervical lymph nodes with a well-defined primary site
documented clinically or radiologically is acceptable; in patients with carcinoma of
unknown primary this will be sufficient for pathologic confirmation without a
clinically or radiographically defined primary site
• For patients with oropharyngeal cancer (OPC)/cancer of unknown primary (CUP):
P16 status based on local site immunohistochemical tissue staining is required. A cell
block obtained from a fine needle aspiration (FNA) biopsy specimen may be used as the sole
diagnostic tissue. Centers are encouraged to contact the pathology chair for clarification
• Note: Institutions must screen patients for p16 status by immunohistochemistry (IHC)
in order to be eligible for the trial using a Clinical Laboratory Improvement
Amendments (CLIA)-certified laboratory. A rigorous laboratory accreditation process
similar to the United States (U.S.) CLIA certification, such as the provincial
accreditation status offered by the Ontario Laboratory Accreditation (OLA) Program in
Canada, the College of American Pathologists (CAP), or an equivalent accreditation in
other countries, is acceptable.
• The p16 results must be reported on the pathology report being submitted. The p16
positivity is defined as > 70% of tumor cells showing strong nuclear and/or
cytoplasmic immunostaining with p16 antibody.
• For patients with laryngeal and hypopharyngeal primaries: Analysis of p16 status
is NOT required
• Patients must have clinically or radiographically evident measurable disease
at the primary site or at nodal stations. Simple tonsillectomy or local
excision of the primary without removal of nodal disease is permitted, as is
excision removing gross nodal disease but with intact primary site. Limited
neck dissections retrieving =< 4 nodes are permitted and considered as
non-therapeutic nodal excisions
• Clinical stage (American Joint Committee on Cancer [AJCC], 8th ed.),
including no distant metastases based on the following diagnostic workup:
• History/physical examination within 60 days prior to registration
• One of the following imaging studies is required within 60 days prior to
registration:
• Computed tomography (CT) scan of neck (diagnostic quality with contrast, unless
contraindicated) OR
• Magnetic resonance imaging (MRI) of the neck (diagnostic quality with contrast, unless
contraindicated) OR
• Fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/CT of the neck; the CT
component must be of diagnostic quality with contrast, unless contraindicated.
• Note: A diagnostic quality CT or MRI with contrast or FDG-PET/CT scan of neck
performed for the purposes of radiation planning may serve as both staging and
planning tools
• One of the following imaging studies is required within 60 days prior to
registration:
• FDG-PET/CT of the chest; FDG-PET/CT scan is strongly preferred and highly recommended
to be used for eligibility OR
• Chest CT
• Exam with laryngopharyngoscopy (mirror or in office direct procedure acceptable)
within 70 days prior to registration;
• Eligibility by patient cohort;
• Non-OPC/p16-negative OPC Cohort; Tumor Site: Larynx/Hypopharynx; Clinical Staging
(AJCC, 8th ed.): T3-4 N0 or T1-4 N1-3 T2 N0 (hypopharynx only)
• Tumor Site: p16-negative OPC; Clinical Staging (AJCC, 8th ed.): T2N1, T1-4 N2-3,
or T3-4 N0-1
• p16-positive OPC/CUP Cohort;
• Tumor Site: OPC; Smoking Status: =< 10 pack-years; Clinical Staging (AJCC, 8th
ed.): T1-3 N2-3 or T4 N0-3
• Tumor Site: OPC; Smoking Status: > 10 pack-years; Clinical Staging (AJCC, 8th
ed.): T1N2-3, T2N1-3 or T3-4 N0-3
• Tumor Site: CUP; Smoking Status: Any; Clinical Staging (AJCC, 8th ed.): T0 N2-3
Note: Cigar and pipe tobacco consumption is not included in calculating the lifetime
pack-years. Marijuana consumption is likewise not considered in this calculation. There is
also no clear scientific evidence regarding the role of chewing tobacco-containing products
in oropharyngeal cancer, although this is possibly more concerning given the proximity of
the oral cavity and oropharynx. In any case, investigators should not count use of
non-cigarette tobacco products in the pack-years calculation.
• Age >= 18
• Zubrod (Eastern Cooperative Oncology Group [ECOG]) performance status of 0-1 within 14
days prior to registration
• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (within 30 days prior to
registration)
• Platelets >= 75,000 cells/mm^3 (within 30 days prior to registration)
• Hemoglobin >= 8.0 g/dL (within 30 days prior to registration)
• Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >=
8.0 g/dL is acceptable)
• Calculated creatinine clearance (CrCl) >= 50 mL/min by the Cockcroft-Gault formula
(within 30 days prior to registration)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 30 days
prior to registration) (not applicable to patients with known Gilbert's syndrome)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 1.5 x
institutional ULN (within 30 days prior to registration)
• Known human immunodeficiency virus (HIV) infected patients on effective
anti-retroviral therapy with undetectable viral load within 6 months and CD4 T Cell
count > 200 cells/mm^3 are eligible for this trial. Testing is not required for entry
into protocol
• Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial
• Negative urine or serum pregnancy test (in persons of childbearing potential) within
14 days prior to registration. Childbearing potential is defined as any person who has
experienced menarche and who has not undergone surgical sterilization (hysterectomy or
bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically
as 12 months of amenorrhea in a woman over 45 in the absence of other biological or
physiological causes
• Willing to use highly effective contraceptives for participants of childbearing
potential (participants who may become pregnant or who may impregnate a partner)
during therapy and for 14 months (females); for 11 months (males) following last dose
of cisplatin; this inclusion is necessary because the treatment in this study may be
significantly teratogenic
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry and, for patients treated in the United States
(U.S.), authorization permitting release of personal health information
Exclusion Criteria:
• Patients with oral cavity cancer, nasopharynx cancer, or p16-negative cancer of
unknown primary (CUP)
• Recurrence of the study cancer
• Definitive clinical or radiologic evidence of distant metastatic disease
• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
different cancer is allowable, however, any prior exposure to cisplatin is excluded
• Prior radiotherapy to the region of the study cancer that would result in overlap of
radiation therapy fields
• Severe, active co-morbidity defined as follows:
• Unstable angina requiring hospitalization in the last 6 months
• Myocardial infarction within the last 6 months
• New York Heart Association Functional Classification III/IV (Note: Patients with
known history or current symptoms of cardiac disease, or history of treatment
with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification.)
• Persistent grade 3-4 (CTCAE version 5.0) electrolyte abnormalities that cannot be
reversed despite replacement as indicated by repeat testing
• Patient must not have an active infection requiring IV antibiotics prior to
registration;
• Other chronic renal disease like nephrotic syndrome, that could be worsened by
cisplatin therapy
• History of allogenic organ transplantation
• Any symptomatic peripheral sensory neuropathy grade >= 2 (CTCAE version 5.0);
• Pregnancy and individuals unwilling to discontinue nursing
• History of hypersensitivity to cisplatin or platinum-containing compounds
Lip, Oral Cavity and Pharynx, Larynx, Unknown Sites, Head and Neck, Advanced Head and Neck Squamous Cell Carcinoma, Advanced Hypopharyngeal Squamous Cell Carcinoma, Advanced Laryngeal Squamous Cell Carcinoma, Advanced Oropharyngeal Squamous Cell Carcinoma, Squamous Cell Carcinoma of Unknown Primary
MSC in Patients With Xerostomia Post XRT in Head and Neck Cancer
This is a single center pilot study designed to determine the safety and tolerability of
autologous bone marrow-derived Mesenchymal Stromal Cells (MSCs) in patients with xerostomia
(dry mouth) after undergoing radiation therapy (XRT) for head and neck cancer (HNC). Up to 12
participants will be enrolled and can expect to be on study for up to 2 years.
Randall Kimple, MD, PhD
All
18 Years to 90 Years old
Phase 1
This study is NOT accepting healthy volunteers
NCT04489732
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Inclusion Criteria:
• Willing to provide informed consent
• Willing to comply with all study procedures and be available for the duration of the
study
• Histological diagnosis of Head and Neck Cancer (HNC) and ≥ 2 years from completion of
treatment for HNC, either clinically or radiologically No Evidence of Disease (NED),
as assessed by ENT or Radiation Oncologist within 28 days of study registration
• Individuals at least 18 years of age and no older than 90 years of age
• Xerostomia defined as less than or equal to 80 percent of baseline (pre-radiation)
salivary function per patient estimate
• Karnofsky performance status ≥ 70, patient eligible for bone marrow aspirate with
wakeful anesthesia
• Radiographically confirmed bilateral submandibular glands
• Females of childbearing potential must agree to have a negative urine or serum
pregnancy test within 7 days prior to bone marrow biopsy. A female of child-bearing
potential is any woman (regardless of sexual orientation, having undergone a tubal
ligation, or remaining celibate by choice) who meets the following criteria:
• has not undergone a hysterectomy or bilateral oophorectomy; or
• has not been naturally postmenopausal for at least 12 consecutive months (i.e.,
has had menses at any time in the preceding 12 consecutive months)
• Women of childbearing potential in sexual relationships with men must have used an
acceptable method of contraception for 30 days prior to study registration and agree
to use an acceptable method of contraception until 4 weeks after completing study
treatment. Males must agree to avoid impregnation of women during and for four weeks
after completing study treatment through use of an acceptable method of contraception.
Note: Acceptable method of contraception includes, but is not limited to, barrier with
additional spermicidal foam or jelly, intrauterine device, hormonal contraception (started
at least 30 days prior to study enrollment), intercourse with men who underwent vasectomy)
Exclusion Criteria:
• History of sialolithiasis
• Patients with one submandibular gland
• History of autoimmune diseases affecting salivary glands, including Sjögren's
syndrome, lupus, scleroderma, type I diabetes, sarcoidosis, and amyloidosis
• Chronic graft vs host disease
• Untreated oral candidiasis
• Use of anti-cholinergic medications (e.g. atropine, ipratropium, oxybutynin,
scopolamine, solifenacin, tiotropium, etc…) while enrolled on study
• Malignancy within the past 2 years, except adequately treated stage I lung cancer, low
risk prostate cancer that has been treated or is undergoing active surveillance,
adequately treated non-melanoma skin cancer, adequately treated ductal carcinoma in
situ (DCIS), or adequately treated stage I cervical cancer
• Expected life expectancy ≤ 6 months
• Lidocaine allergy
• Use of investigational drugs, biologics, or devices within 30 days prior to enrollment
• Women who are pregnant, lactating or planning on becoming pregnant during the study
• Not suitable for study participation due to other reasons at the discretion of the
investigators
Xerostomia Following Radiotherapy, Lip, Oral Cavity and Pharynx, Head and Neck
A Study to Compare Early Use of Vinorelbine and Maintenance Therapy for Patients With High Risk Rhabdomyosarcoma
This phase III trial compares the safety and effect of adding vinorelbine to vincristine,
dactinomycin, and cyclophosphamide (VAC) for the treatment of patients with high risk
rhabdomyosarcoma (RMS). High risk refers to cancer that is likely to recur (come back) after
treatment or spread to other parts of the body. This study will also examine if adding
maintenance therapy after VAC therapy, with or without vinorelbine, will help get rid of the
cancer and/or lower the chance that the cancer comes back. Vinorelbine and vincristine are in
a class of medications called vinca alkaloids. They work by stopping cancer cells from
growing and dividing and may kill them. Dactinomycin is a type of antibiotic that is only
used in cancer chemotherapy. It works by damaging the cell's deoxyribonucleic acid (DNA) and
may kill cancer cells. Cyclophosphamide is in a class of medications called alkylating
agents. It works by damaging the cell's DNA and may kill cancer cells. It may also lower the
body's immune response. Vinorelbine, vincristine, dactinomycin and cyclophosphamide are
chemotherapy medications that work in different ways to stop the growth of cancer cells,
either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. This trial may have the potential to eliminate rhabdomyosarcoma for a long time or
for the rest of patient's life.
Kenneth Desantes, M.D.
All
up to 50 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04994132
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Inclusion Criteria:
• Patients must be =< 50 years of age at the time of enrollment
• Patients with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based
upon institutional histopathologic classification are eligible to enroll on the study
based upon stage, group, and age, as below. FOXO1 fusion status must be determined by
week 4 (day 28) of therapy. RMS types included under embryonal RMS (ERMS) include
those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as
ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the
2020 World Health Organization (WHO) Classification as ERMS (classic, dense and
botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical
spindle cell ERMS variant and the newly recognized sclerosing RMS variant).
Classification of alveolar RMS (ARMS) in the 2020 WHO Classification is the same as in
the ICR and includes classic and solid variants
• ERMS
• Stage 4, group IV, >= 10 years of age
• ARMS
• Stage 4, group IV Patients will be eligible to remain on protocol therapy
based upon stage, group, and age
• Bone marrow metastatic disease is based on morphologic evidence of RMS based on
hematoxylin and eosin (H&E) stains. In the absence of morphologic evidence of marrow
involvement on H&E, patients with bone marrow involvement detected ONLY by flow
cytometry, reverse transcriptase (RT)-polymerase chain reaction (PCR), fluorescence in
situ hybridization (FISH), or immunohistochemistry will NOT be considered to have
clinical bone marrow involvement for the purposes of this study
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (must be
performed within 7 days prior to enrollment):
• Age; Maximum serum creatinine (mg/dL)
• 1 month to < 6 months; 0.4 mg/dL (male); 0.4 mg/dL (female)
• 6 months to < 1 year; 0.5 mg/dL (male); 0.5 mg/dL (female)
• 1 to < 2 years; 0.6 mg/dL (male); 0.6 mg/dL (female)
• 2 to < 6 years; 0.8 mg/dL (male); 0.8 mg/dL (female)
• 6 to < 10 years; 1 mg/dL (male); 1 mg/dL (female)
• 10 to < 13 years; 1.2 mg/dL (male); 1.2 mg/dL (female)
• 13 to < 16 years; 1.5 mg/dL (male); 1.4 mg/dL (female)
• >= 16 years; 1.7 mg/dL (male); 1.4 mg/dL (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (must be performed within
7 days prior to enrollment)
• If there is evidence of biliary obstruction by tumor, then total bilirubin must
be < 3 x ULN for age
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Exclusion Criteria:
• Patients with evidence of uncontrolled infection are not eligible
• RMS that is considered a second malignancy and previous cancer(s) that were treated
with chemotherapy and/or radiation. Surgical resection alone of previous cancer(s) is
allowed
• Patients with central nervous system involvement of RMS as defined below:
• Malignant cells detected in cerebrospinal fluid
• Intra-parenchymal brain metastasis separate and distinct from primary tumor
(i.e., direct extension from parameningeal primary tumors is allowed).
• Diffuse leptomeningeal disease
• Patients who have received any chemotherapy (excluding steroids) and/or radiation
therapy for RMS prior to enrollment.
• Note: the following exception:
• Patients requiring emergency radiation therapy for RMS. These patients are
eligible, provided they are consented to ARST2031 prior to administration of
radiation
• Note: Patients who have received or are receiving chemotherapy or radiation for
non-malignant conditions (e.g. autoimmune diseases) are eligible. Patients must
discontinue chemotherapy for non-malignant conditions prior to starting protocol
therapy
• Vincristine and vinorelbine are sensitive substrates of CYP450 3A4 isozyme. Patients
must not have received drugs that are moderate to strong CYP3A4 inhibitors and
inducers within 7 days prior to study enrollment
• Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs. A pregnancy test is required for female
patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation
Alveolar Rhabdomyosarcoma, Botryoid-Type Embryonal Rhabdomyosarcoma, Embryonal Rhabdomyosarcoma, Metastatic Embryonal Rhabdomyosarcoma, Metastatic Rhabdomyosarcoma, Solid Alveolar Rhabdomyosarcoma, Spindle Cell Rhabdomyosarcoma, Spindle Cell/Sclerosing Rhabdomyosarcoma, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Soft Tissue, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Thyroid, Other Endocrine System, Bladder, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma
Testing the Addition of the Drug Atezolizumab to the Usual Radiation Treatment for Patients With Early Non-small Cell Lung Cancer
This phase III trial studies how well atezolizumab added to the usual radiation therapy works
in treating patients with stage I-IIA non-small cell lung cancer. Immunotherapy with
monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the
cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation
therapy, such as stereotactic body radiation therapy, uses special equipment to position a
patient and deliver radiation to tumors with high precision. This method can kill tumor cells
with fewer doses over a shorter period and cause less damage to normal tissue. Giving
atezolizumab and radiation therapy may work better than radiation therapy alone in treating
patients with early non-small cell lung cancer.
Andrew Baschnagel, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04214262
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Inclusion Criteria:
• Patient must have histologically or cytologically proven stage I-IIA or limited T3N0M0
non-small cell lung cancer (NSCLC), without radiographic evidence of nodal or distant
involvement (N0M0). Patient may have T3 disease with the exclusion of pericardial
involvement. Patients with multifocal tumors with no more than two lesions confirmed
or suspected to be synchronous early stage NSCLCs are eligible provided at least one
lesion is histologically or cytologically proven to be NSCLC and meets one or more
high-risk features
• Disease must have one or more of the following high-risk features:
• Tumor diameter >= 2 cm (inclusive of any non-solid, ground glass component) as
assessed by diagnostic CT
• Tumor standard uptake value (SUV) max >= 6.2 as assessed by FDG PET/CT
• Moderately differentiated, poorly differentiated, or undifferentiated histology
• Patient must have undergone diagnostic chest CT with or without contrast (IV contrast
preferred) within 42 days prior to randomization. PET-CT may be used if the CT portion
is of comparable diagnostic quality to a stand-alone CT. All disease must be assessed
within 42 days prior to randomization
• Patient must have undergone FDG PET/CT of chest within 90 days prior to randomization
• Patient must not have evidence of hilar or mediastinal nodal involvement. Any patient
with radiographically suspicious hilar or mediastinal nodes (including features such
as non-calcified nodes with a short axis diameter > 1 cm, abnormal morphology, and/or
elevated FDG avidity) must undergo cytologic sampling of suspicious nodes to rule out
involvement prior to randomization. Mediastinal nodal sampling for other patients is
optional. For cases in which the treating physician/multidisciplinary opinion is used
to define nodes as "non-suspicious" (such as long-standing, stable enlarged nodes from
other medical causes), the rationale must be clearly documented within the medical
record
• Patient must have undergone history and physical examination within 28 days prior to
randomization
• Patient must be medically or surgically inoperable as documented by a board certified
thoracic surgeon or multi-disciplinary tumor board consensus OR patient's
unwillingness to undergo surgical resection must be clearly documented
• Patient must not have received any prior treatment for the current NSCLC diagnosis
• Patient must not have undergone prior radiation to overlapping regions of the chest
that, in the opinion of the treatment physician, will interfere with protocol
treatment
• Patient must not have received treatment with systemic immunostimulatory or
immunosuppressive agents, including corticosteroids, within 14 days prior to
randomization
• Patient must be >= 18 years old
• Patient must have Zubrod performance status of 0-2
• Patient must have adequate liver function defined as aspartate aminotransferase (AST)
and alanine aminotransferase (ALT) =< 3 x institutional upper level of normal (IULN)
within 28 days prior to randomization
• Patient must have adequate renal function defined as calculated creatinine clearance
>= 30 mL/min using the following formula. The serum creatinine value used in the
calculation must have been collected within 28 days prior to randomization
• Patient must have absolute neutrophil count (ANC), platelets, and hemoglobin measured
within 28 days prior to randomization. The purpose of these tests is to collect
baseline values to compare with on-treatment values
• Patient must have thyroid-stimulating hormone (TSH) measured within 28 days prior to
randomization. The purpose of this test is to collect baseline values to compare with
on-treatment values
• Patient must not have significant cardiovascular disease (New York Heart Association
[NYHA] class II or greater)
• Patient must not have myocardial infarction within 90 days prior to randomization
• Patient must not have unstable arrhythmias or unstable angina
• Patient must not have known left ventricular ejection fraction (LVEF) < 40% within 28
days prior to randomization
• NOTE: Assessment of LVEF by echocardiogram or multigated acquisition (MUGA) is
not an eligibility requirement, but if a standard of care echocardiogram or MUGA
was clinically indicated, the LVEF must not be < 40% within 28 days prior to
randomization
• Patient must not have had an infection >= grade 3 (Common Terminology Criteria for
Adverse Events [CTCAE] version 5.0) within 28 days prior to randomization
• Patient must not have an active autoimmune disease that has required systemic
treatment in past two years (i.e., with use of disease modifying agents,
corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine,
insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is not considered a form of systemic treatment and is allowed
• Patient must be tested for hepatitis B within 28 days prior to randomization. Patient
must not have active (chronic or acute) hepatitis B virus (HBV) infection. Patients
may have past or resolved HBV infection
• Active HBV is defined as having a positive hepatitis B surface antigen (HBsAg)
test
• Past or resolved HBV is defined as having a negative HBsAG test and a positive
total hepatitis B core antibody (HBcAb) test
• Patient must be tested for hepatitis C within 28 days prior to randomization. Patient
must not have active hepatitis C virus (HCV) infection
• Active HCV is defined as having a positive HCV antibody test followed by a
positive HCV ribonucleic acid (RNA) test
• Patient must have pulmonary function testing to include, at a minimum, forced
expiratory volume in 1 second (FEV1) and Diffusing capability of carbon monoxide
(DLCO) documented within 90 days prior to randomization
• Patients with known human immunodeficiency virus (HIV) infection must be receiving
anti-retroviral therapy and have an undetectable viral load at their most recent viral
load test within 6 months prior to randomization
• Patient must not have a history of clinically significant interstitial lung disease or
evidence of active pneumonitis on the screening chest CT
• Patients must not have a prior or concurrent malignancy whose natural history or
treatment has the potential (in the opinion of the treating physician) to interfere
with the safety or efficacy assessment of the investigational regimen
• Patients must not be pregnant due to the potential teratogenic side effects of the
protocol treatment. Women of reproductive potential and men must have agreed to use an
effective contraception method for the duration of protocol treatment, and for 5
months (150 days) after the last dose of atezolizumab. A woman is considered to be of
"reproductive potential" if she has had a menses at any time in the preceding 12
consecutive months. In addition to routine contraceptive methods, "effective
contraception" also includes heterosexual celibacy and surgery intended to prevent
pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy,
bilateral oophorectomy or bilateral tubal ligation. However, if at any point a
previously celibate patient chooses to become heterosexually active during the time
period for use of contraceptive measures outlined in the protocol, he/she is
responsible for beginning contraceptive measures. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with atezolizumab, breastfeeding must be discontinued prior to randomization
• Patients of reproductive potential must have a negative serum pregnancy test within 14
days prior to randomization
• Patients must not have known active tuberculosis
• Patients must not have received a live, attenuated vaccine within 28 days prior to
randomization
• NOTE: All coronavirus disease 2019 (COVID-19) vaccines that have received Food
and Drug Administration (FDA) approval or FDA emergency use authorization are
acceptable
• Patients must not have a known history of allergic reactions attributed to compounds
of similar chemical or biologic composition to atezolizumab
• Patients must not have a known history of severe allergic, anaphylactic, or other
hypersensitivity reactions to chimeric antibodies, fusion proteins, or Chinese hamster
ovary cell products or to any component of the atezolizumab formulation
• Patient must agree to have specimens submitted for translational medicine and banking
• Patients must be informed of the investigational nature of this study and must sign
and give written informed consent in accordance with institutional and federal
guidelines
• As a part of the OPEN registration process the treating institution's identity is
provided in order to ensure that the current (within 365 days) date of institutional
review board approval for this study has been entered in the system
• Patients who can complete quality of life instruments in English, French, or Spanish
must agree to complete the questionnaires at the protocol-specified time points
Lung, Lung Non-Small Cell Carcinoma, Stage I Lung Cancer AJCC v8, Stage II Lung Cancer AJCC v8
Clinical Trial of Alpelisb and Tucatinib in Patients With PIK3CA-Mutant HER2+ Metastatic Breast Cancer.
Phase IB/II clinical trial of Alpelisb and Tucatinib in patients with PIK3CA-Mutant
HER2-positive metastatic breast cancer.
Marina Sharifi, MD, PhD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05230810
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Criteria:
Inclusion criteria:
1. Women and men ≥ 18 years old are eligible to enroll
2. ECOG performance status 0-1
3. Life expectancy of more than 6 months, in the opinion of the investigator
4. Histologically confirmed diagnosis of HER2+ locally advanced unresectable or
metastatic breast cancer. HER2 positivity is defined by fluorescence in situ
hybridization (FISH) and/or 3+ staining by IHC according to the latest ASCO/CAP
guidelines.
5. Documented presence of activating mutation in PIK3CA in the tumor, based on the
analysis of solid or liquid biopsy by an assay approved for clinical decision makingby
an FDA-approved test (examples include FoundationOne Liquid®; Guardant360®,
Therrascreen® PIK3CA).
6. Known ER and PR status of the tumor defined by IHC according to the latest ASCO/CAP
guidelines
7. Patients with HR-/HER2+ or HR+/HER2+ breast cancer may enroll
8. HR+/HER2+ patients should be men or post-menopausal women; premenopausal women with
HR+/HER2+ breast cancer are eligible if on ovarian suppression, or agreeable to
mandatory ovarian suppression
9. HR+/HER2+ patients should be agreeable to concomitant treatment with fulvestrant per
study protocol. Prior therapy with fulvestrant is allowed.
10. Patients should have received at least two FDA-approved HER2-targeted agents at any
time in the course of their disease. Note: 1 line of therapy containing EGFR or
HER2-tyrosine kinase inhibitors (for example, neratinib, tucatinib, lapatinib,
afatinib, pyrotinib, etc.) in the metastatic setting is allowed
11. Measurable and/or evaluable disease per RECIST 1.1 criteria and/or RANO-BM criteria
(appendix C). Bone only disease is allowed.
12. CNS inclusion criteria:
Based on screening contrast brain MRI, patients must have one of the following:
1. No evidence of brain metastases 2. Untreated brain metastases not needing immediate
local therapy. For patients with untreated CNS lesions > 2.0 cm on screening contrast brain
MRI, discussion with and approval from the medical monitor is required prior to enrollment
3. Previously treated brain metastases
a. Brain metastases previously treated with local therapy may either be stable since
treatment or may have progressed since prior local CNS therapy, provided that there is no
clinical indication for immediate re-treatment with local therapy in the opinion of the
investigator b. Patients treated with CNS local therapy for newly identified lesions found
on contrast brain MRI performed during screening for this study may be eligible to enroll
if all of the following criteria are met: i. Time since WBRT is ≥ 21 days prior to first
dose of treatment, time since surgical resection of CNS metastases is ≥ 14 days prior to
the first dose of study treatment, or time since SRS is ≥ 7 days prior to first dose of
treatment.
ii. Other sites of disease evaluable by RECIST 1.1 or RANO-BM are present c. Relevant
records of any CNS treatment must be available to allow for classification of target and
non-target lesions. 13. Adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1,500/mm3
• Platelets ≥ 75,000/mm3
• Hemoglobin ≥ 9.0 mg/dL without red blood cell transfusion ≤ 7 days prior to Cycle 1
Day 1 of therapy
• Total serum bilirubin ≤ 1.5 X upper limit of normal (ULN) except for subjects with
known Gilbert's disease, who may enroll if the conjugated bilirubin is ≤ 1.5 ULN
• AST (SGOT)/ALT (SGPT) ≤2.5 X ULN;
• Serum creatinine Estimated creatinine clearance ≥50 mL/min as calculated by
Cockroft-Gault formula; actual body weight must be used for creatinine clearance
calculations unless BMI > 30 kg/m2 then lean body weight must be used;≤ 1.5 mg/dL
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT)
≤ 1.5 X ULN unless on medication known to alter INR and aPTT
• Fasting blood glucose ≤140 mg/dL
• HbA1C≤6.4%
• Left ventricular ejection fraction (LVEF) ≥ 50% (as assessed by ECHO or MUGA)
documented within 4 weeks prior to first dose of study treatment
• Serum or urine pregnancy test (for women of childbearing potential, defined as
premenopausal women who are not permanently sterile due to hysterectomy, bilateral
oophorectomy, bilateral tubal ligation, or bilateral tubal occlusion) negative ≤ 7
days of starting treatment 14. Patients with body mass index >25, or FBG 110-140mg/dL,
or HbA1C 5.7 •6.4% should be agreeable for low glycemic diet and lifestyle
modifications, and consulted by nutritionist prior to initiation of the study drugs.
Ability to understand and the willingness to sign a written informed consent and
comply with the study scheduled visits, treatment plans, laboratory tests and other
procedures.
Exclusion criteria:
1. Patients with contraindications to undergo contrast MRI imaging of the brain are
excluded from the study
2. Pregnancy or breast feeding
3. Any systemic anti-cancer therapy (including hormonal therapy or investigational
agents) or surgery in <14 days prior to the first dose of study treatment WBRT in <21
days, SBRT for CNS disease in <7 days, or palliative radiation to extracranial sites
in <14 days prior to the first dose of study treatment5.
4. Based on screening brain MRI, patients must not have any of the following:
1. Any untreated brain lesions > 2.0 cm in size, unless discussed with medical monitor and
approval for enrollment is given 2. Ongoing use of systemic corticosteroids for control of
symptoms of brain metastases at a total daily dose of > 2 mg of dexamethasone (or
equivalent). However, patients on a chronic stable dose of ≤ 2 mg total daily of
dexamethasone (or equivalent) may be eligible with discussion and approval by the medical
monitor 3. Any brain lesion thought to require immediate local therapy, including (but not
limited to) a lesion in an anatomic site where increase in size or possible
treatment-related edema may pose risk to patient (e.g. brain stem lesions). Patients who
undergo local treatment for such lesions identified by screening contrast brain MRI may
still be eligible for the study based on criteria described under CNS inclusion criteria 3b
4. Known or suspected leptomeningeal disease as documented by the investigator 5. Have
poorly controlled (> 1/week) generalized or complex partial seizures, or manifest
neurologic progression due to brain metastases notwithstanding CNS-directed therapy 5. Any
toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1, with the
exception of peripheral neuropathy, which must have resolved to ≤ Grade 2, and alopecia 6.
More than 1 line of therapy containing tucatinib, lapatinib, neratinib, afatinib,
pyrotinib, or other EGFR or HER2 tyrosine kinase inhibitor in the metastatic setting. Note:
receiving the above medications for <30 days is not considered to be a "line of therapy".
Adjuvant treatment with EGFR or HER2 tyrosine kinase inhibitors does not count.
7. Previous treatment with alpelisib or other PI3K, mTOR or AKT inhibitor of more than 30
days duration.
8. An established diagnosis of diabetes mellitus type I, or uncontrolled diabetes mellitus
type II 9. History of acute pancreatitis within 1 year of screening, or a past medical
history of chronic pancreatitis 10. History of severe cutaneous hypersensitivity reactions
(Steven Johnson syndrome, erythema multiforme or toxic epidermal necrolysis) 11. Active
bacterial, fungal or viral infections requiring treatment with IV antibiotic, IV
anti-fungal, or IV anti-viral drugs 12. Known active hepatitis B (HBV) or, active hepatitis
C (HCV) or human immunodeficiency virus (HIV) infections. Note: pretesting is not required.
Patients with history of treated and cured HCV infection may enroll if they have documented
undetectable viral load.
13. Known HIV infection with CD4+ T-cell (CD4+) counts < 350 cells/μL. Note: pretesting is
not required. Patients with known HIV infection and CD4+ T-cell (CD4+) counts ≥ 350
cells/μL may enroll.
14. Inability to swallow pills or any significant gastrointestinal disease which would
preclude the adequate oral absorption of medications 15. Use of prohibited medications
listed in the Appendix D (strong CYP3A4 inducers or inhibitors, and strong CYP2C8 inducers
or inhibitors) within 3 elimination half-lives prior to initiation of study treatments 16.
Myocardial infarction, severe/unstable angina, percutaneous transluminal coronary
angioplasty/stenting (PTCA), or coronary artery bypass graft (CABG) within 6 month of the
first dose of the study treatment 17. Clinically significant cardio-vascular disease, such
as ventricular arrhythmia requiring therapy, uncontrolled hypertension (defined as
persistent systolic blood pressure > 160 mm Hg and/or diastolic blood pressure > 100 mm Hg
on antihypertensive medications), or any history of symptomatic congestive heart failure
(CHF) 18. Other severe acute or chronic medical or psychiatric conditions or laboratory
abnormalities that may increase the risk associated with study participation or study drug
administration, or may interfere with the interpretation of study results, or in the
judgment of the investigator would make the subject inappropriate for entry into the study.
Study of GS-1811 Given Alone or With Zimberelimab in Adults With Advanced Solid Tumors
This is a first-in-human (FIH) study to evaluate the safety and tolerability and to determine
the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of GS-1811 as
monotherapy and in combination with zimberelimab in participants with advanced solid tumors.
This study will be conducted in 6 parts (Parts A, B, and E: monotherapy, Parts C and D:
combination therapy, and Part F for both monotherapy and combination therapy) in participants
with advanced solid tumors who have received, been intolerant to, or been ineligible for all
treatments known to confer clinical benefit or in participants with select solid tumors.
Nataliya Uboha, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05007782
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Key
Inclusion Criteria:
• Disease:
• Part A: Individuals with histologically or cytologically confirmed advanced solid
tumors who have received, been intolerant to, or been ineligible for all
treatment known to confer clinical benefit.
• Part B: Individuals with histologically or cytologically confirmed select
indications who have received, been intolerant to, or been ineligible for all
treatment known to confer clinical benefit.
• Part C: Individuals with histologically or cytologically confirmed advanced solid
tumors who have received, been intolerant to, or been ineligible for all
treatments known to confer clinical benefit or whose disease is indicated for
anti- programmed cell death protein 1 or programmed cell death ligand 1 (PD-[L]1)
monoclonal antibody monotherapy.
• Part D: Individuals with pathologically confirmed select advanced solid tumors.
• Part E: Individuals with pathologically confirmed select advanced solid tumors.
Participants must have received, have been intolerant to, or have been ineligible
for all treatment known to confer clinical benefit.
• Part F: Individuals with pathologically-confirmed select advanced solid tumors.
Participants must have received, have been intolerant to, or have been ineligible
for all treatments known to confer clinical benefit; or, for participants who
will undergo combination therapy, have disease which is indicated for
anti-PD-(L)1 mAb monotherapy.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 for
individuals in Parts A, B, and C, and 0 or 1 for individuals in Parts D, E, and F.
• Adequate organ function.
• Male individuals and female individuals of childbearing potential who engage in
heterosexual intercourse must agree to use methods of contraception.
• Tissue requirement:
• Parts A, C, D, E and F: Must provide pre-treatment adequate tumor tissue sample
prior to enrollment.
• Part B and select participants in Parts C and F: Must have fresh pre-treatment
and on-treatment biopsies for biomarker analysis.
Key
Exclusion Criteria:
• Concurrent anticancer treatment.
• Any anti-cancer therapy, whether investigational or approved, within protocol
specified time prior to initiation of study including: immunotherapy or biologic
therapy (< 28 days), chemotherapy (< 21 days), targeted small molecule therapy (< 14
days), hormonal therapy or other adjunctive therapy (< 14 days) or radiotherapy (< 21
days).
• Any prior CCR8 directed therapy.
• Prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell
transplantation. Exception: prior corneal transplant without requirement for systemic
immunosuppressive agents is allowed.
• Concurrent active malignancy other than nonmelanoma skin cancer, curatively resected
carcinoma in situ, localized prostate cancer, or superficial bladder cancer after
undergoing potentially curative therapy with no evidence of disease. Individuals with
other previous malignancies are eligible if disease-free for > 2 years.
• History of intolerance, hypersensitivity, or treatment discontinuation due to severe
immune-related adverse events (irAEs) on prior immunotherapy.
• History of autoimmune disease or active autoimmune disease requiring systemic
treatment within 2 years.
• History of pneumonitis, interstitial lung disease, or severe radiation pneumonitis
(excluding localized radiation pneumonitis).
• Active and clinically relevant bacterial, fungal, or viral infection that is not
controlled or requires IV antibiotics.
• Active hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and/or human
immunodeficiency virus (HIV).
• Positive serum pregnancy test or breastfeeding female.
• Live vaccines within 30 days prior to first dose.
• Significant cardiovascular disease.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Advanced Solid Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
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