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 of a New Way to Treat Children and Young Adults With a Brain Tumor Called NGGCT
This phase II trial studies the best approach to combine chemotherapy and radiation therapy
(RT) based on the patient's response to induction chemotherapy in patients with
non-germinomatous germ cell tumors (NGGCT) that have not spread to other parts of the brain
or body (localized). This study has 2 goals: 1) optimizing radiation for patients who respond
well to induction chemotherapy to diminish spinal cord relapses, 2) utilizing higher dose
chemotherapy followed by conventional RT in patients who did not respond to induction
chemotherapy. Chemotherapy drugs, such as carboplatin, etoposide, ifosfamide, and thiotepa,
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 or high-energy protons to kill tumor cells and shrink tumors. Studies have
shown that patients with newly-diagnosed localized NGGCT, whose disease responds well to
chemotherapy before receiving radiation therapy, are more likely to be free of the disease
for a longer time than are patients for whom the chemotherapy does not efficiently eliminate
or reduce the size of the tumor. The purpose of this study is to see how well the tumors
respond to induction chemotherapy to decide what treatment to give next. Some patients will
be given RT to the spine and a portion of the brain. Others will be given high dose
chemotherapy and a stem cell transplant before RT to the whole brain and spine. Giving
treatment based on the response to induction chemotherapy may lower the side effects of
radiation in some patients and adjust the therapy to a more efficient one for other patients
with localized NGGCT.
Kenneth Desantes, M.D.
All
3 Years to 29 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT04684368
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Inclusion Criteria:
• Patients must be >= 3 years and < 30 years at the time of study enrollment
• Patients must be newly diagnosed with localized primary CNS NGGCT of the suprasellar
and/or pineal region by pathology and/or serum or cerebrospinal fluid (CSF) elevation
of AFP above institutional normal or > 10 ng/mL or human chorionic gonadotropin (hCG)
beta > 100 mIU/mL as confirmed by Rapid Central Marker Screening Review on
APEC14B1-CNS. Suprasellar, pineal and bifocal tumors are included. (CSF tumor markers
and cytology must be within 31 days prior to enrollment and start of protocol therapy
[repeat if necessary]. Serum tumor markers, AFP and hCGbeta must be within 7 days
prior to enrollment and start of protocol therapy [repeat if necessary]). Basal
ganglia or other primary sites are excluded
• Patients with any of the following pathological elements are eligible: endodermal
sinus (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratoma
and mixed germ cell tumor (GCT) (i.e., may include some pure germinoma) if malignant
elements listed above are present. Patients with only mature teratoma are excluded.
Patients with pure germinoma admixed with mature teratoma are excluded (would be
eligible for pure germinoma protocols)
• Patients must have a cranial MRI with and without gadolinium at diagnosis/prior to
enrollment. If surgical resection is performed, patients must have pre-operative and
post operative brain MRI with and without gadolinium. The post operative brain MRI
should be obtained within 72 hours of surgery. If patient has a biopsy only,
post-operative brain MRI is recommended but not required (within 31 days prior to
study enrollment and start of protocol therapy )
• Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to
enrollment. Spine MRI with and without gadolinium is recommended (within 31 days prior
to study enrollment and start of protocol therapy)
• Lumbar CSF must be obtained prior to study enrollment unless medically
contraindicated. If a patient undergoes surgery and lumbar CSF cytology cannot be
obtained at the time of surgery, then it should be performed at least 10 days
following surgery and prior to study enrollment. False positive cytology can occur
within 10 days of surgery
• Patients must have RAPID CENTRAL TUMOR MARKER REVIEW CSF tumor markers obtained prior
to enrollment unless medically contraindicated. Ventricular CSF obtained at the time
of CSF diversion procedure (if performed) is acceptable for tumor markers but lumbar
CSF is preferred. In case CSF diversion and biopsy/surgery are combined, CSF tumor
markers should be collected first
• Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to
enrollment)
• Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to
enrollment)
• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (within 7 days
prior to 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):
• Age: Maximum serum creatinine (mg/dL)
• 3 to < 6 years: 0.8 (male), 0.8 (female)
• 6 to < 10 years: 1 (male), 1 (female)
• 10 to < 13 years: 1.2 (male), 1.2 (female)
• 13 to < 16 years: 1.5 (male), 1.4 (female)
• >= 16 years: male (1.7), 1.4 (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment)
• Serum glutamate pyruvate 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
• Central nervous system function defined as:
• Patients with seizure disorder may be enrolled if on anticonvulsants and well
controlled
• Patients must not be in status epilepticus, coma or assisted ventilation prior to
study enrollment
• Protocol therapy must begin within 31 calendar days of definitive surgery or clinical
diagnosis, whichever is later. If a biopsy only was performed, the biopsy date will be
considered the date of definitive surgery. For patients who have a biopsy or
incomplete resection at diagnosis followed by additional surgery, the date of the last
resection will be considered the date of definitive surgery.
• 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
• NEUROCOGNITIVE FUNCTION AND QUALITY OF LIFE ASSESSMENT:
• English-, Spanish-, or French- speaking
• Note: Patients who speak a language other than English, Spanish, or French will
be allowed to participate in ACNS2021 but will not complete the neurocognitive
and quality of life assessments
• No known history of neurodevelopmental disorder prior to diagnosis of NGGCT (e.g.,
Down syndrome, fragile X, William syndrome, intellectual disability). Patients with
NF1 will be allowed to participate
• Additional eligibility criteria for the COG Standardized Neuropsychological Battery
only: must be at a site that has a psychologist to administer the battery
• Note: If not eligible for the COG Standardized Battery, patients should still
complete the Behavior Rating Inventory of Executive Function, Second Edition
(BRIEF-2), Pediatric Quality of Life Inventory (PedsQL), Adaptive Behavior
Assessment System Third Edition (ABAS-3), and Behavior Assessment System for
Children, Third Edition (BASC-3) questionnaires
Exclusion Criteria:
• Patients with tumors located outside the ventricles (i.e., basal ganglia, thalamus)
• Patients with only mature teratoma and non-elevated markers upon tumor sampling at
diagnosis
• Patients who have received any prior tumor-directed therapy for their diagnosis of
NGGCT other than surgical intervention and corticosteroids
• Patients with metastatic disease (i.e., MRI evaluation, lumbar CSF cytology or
intraoperative evidence of dissemination)
• Female patients who are pregnant, since fetal toxicities and teratogenic effects have
been noted for several of the study drugs
• Note: Serum and urine pregnancy tests may be falsely positive due to
HCGbeta-secreting germ cell tumors. Ensure the patient is not pregnant by
institutional standards
• 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
Central Nervous System Nongerminomatous Germ Cell Tumor, Choriocarcinoma, Embryonal Carcinoma, Immature Teratoma, Malignant Teratoma, Mixed Germ Cell Tumor, Pineal Region Germ Cell Tumor, Pineal Region Immature Teratoma, Pineal Region Yolk Sac Tumor, Suprasellar Germ Cell Tumor, Brain and Nervous System, Brain/Central Nervous System
This study will use different types of medical imaging to assess how lesions from advanced
prostate cancer become resistant to second-generation AR-targeted therapy, and how the
different types of imaging compare in that assessment. Participants in this study have
advanced prostate cancer and are either scheduled to start a second-generation androgen
receptor (AR) targeted therapy (such as enzalutamide, abiraterone, or apalutamide) or are
already being treated with one. Participants can expect to be in the study for at least 9
months, and up to 2 years.
Christos Kyriakopoulos, MD
Male
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT05647564
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Inclusion Criteria:
• Histologically proven adenocarcinoma of the prostate.
• At least 1 radiographic metastases as seen on conventional CT imaging or bone scan
• Progressive prostate cancer as evident by at least two separate increase in PSA over
nadir, and absolute PSA value at least 2 ng/ml (INTRINSIC RESISTANCE COHORT ONLY)
• Patients must be candidate for a second-generation androgen receptor (AR) inhibitor
(e.g. enzalutamide, abiraterone, apalutamide), or Lu177-PSMA radioligand therapy
(INTRINSIC RESISTANCE COHORT ONLY)
• Men of age >18 years.
• Patients must be able to comply with all study procedures, including having both the
ability and willingness to lie flat for ≥ 30 minutes during imaging
• Patients must be informed of the exploratory nature of the study and its potential
risks, and must sign IRB- approved consent form indicating such understanding.
• Life-expectancy at least 12 months
• Patients currently receiving a second-generation androgen receptor (AR) inhibitor
(e.g. enzalutamide, abiraterone, apalutamide) and must have had 1) PSA decline on
treatment and 2) now have PSA increase over nadir while still on treatment (patients
must be registered within 12 weeks of first documented PSA increase) (ACQUIRED
RESISTANCE COHORT ONLY)
Exclusion Criteria:
• Must not have uncontrolled diabetes (fasting blood sugar > 200 mg/dL or inability to
safely hold diabetes medication or fast 6 hours prior to FDG PET scan)
• Prior treatment with second-generation AR inhibitor for prostate cancer in the
metastatic disease setting (prior second-generation AR inhibitor in the neoadjuvant or
adjuvant setting is permitted unless patient developed progression while on treatment)
(INTRINSIC RESISTANCE COHORT, AR-INHIBITOR GROUP ONLY)
• Pain or clinical symptoms from metastatic prostate cancer requiring opioid analgesics
• Known neuro-endocrine prostate cancer
• Prior radioisotope therapy for castration-resistant prostate cancer
• To avoid the possibility of unintended coercion, vulnerable populations such as
incarcerated subjects, subjects unable to provide their own informed consent and
non-English speaking patients will not be considered
A Study of Zilovertamab Vedotin (MK-2140) as Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (MK-2140-006)
The purpose of this study is to assess the safety and tolerability of zilovertamab vedotin as
monotherapy and in combination in participants with select B-cell lymphomas including mantle
cell lymphoma (MCL), Richter's transformation lymphoma (RTL), follicular lymphoma (FL), and
chronic lymphocytic leukemia (CLL). This study will also evaluate zilovertamab vedotin as
monotherapy and in combination with respect to objective response rate.
- Cohort A: Participants with relapsed or refractory MCL relapsed or refractory disease
after at least 2 prior systemic therapies including a Bruton's tyrosine kinase
inhibition/inhibitor (BTKi), and post therapy chimeric antigen receptor T (CAR-T) cell
therapy or ineligible for CAR-T cell therapy
- Cohort B: Participants with relapsed or refractory RT disease after at least 1 prior
systemic therapy
- Cohort C: Participants with relapsed or refractory MCL relapsed or refractory disease
after at least 1 prior systemic therapy and no prior exposure to a non-covalent BTKi
- Cohort D: Participants with relapsed or refractory FL and CLL relapsed or refractory
disease after at least 2 prior systemic therapies and have no other available therapy
- Cohort E: Participants with relapsed or refractory FL after at least 2 prior systemic
therapies and have no other available therapy
- Cohort F: Participants with relapsed or refractory CLL after at least 2 prior systemic
therapies and have no other available therapy
The primary study hypothesis is that zilovertamab vedotin monotherapy has an increased
Objective Response Rate (ORR) per Lugano Response Criteria as assessed by blinded independent
central review (BICR).
Christopher Fletcher, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05458297
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The main inclusion criteria include, but are not limited to the following:
Inclusion Criteria:
• For aggressive B-cell malignancies MCL: Has histologically confirmed biopsy according
to the 2016 World Health Organization (WHO) classification of neoplasms of the
hematopoietic and lymphoid tissues and has relapsed or refractory disease after at
least 2 prior systemic therapies including a Bruton's tyrosine kinase
inhibition/inhibitor(s) (BTKi), and is post chimeric antigen receptor T (CAR-T) cell
therapy or is ineligible for CAR-T cell therapy.
• For aggressive B-cell malignancies MCL Cohort C: Has histologically confirmed biopsy
according to the 2016 World Health Organization (WHO) classification of neoplasms of
the hematopoietic and lymphoid tissues and has relapsed or refractory disease after at
least 1 prior systemic therapy and has no prior exposure to a non-covalent BTKi.
• For aggressive B-cell malignancies Richter transformation lymphoma (RTL): Has
histologically confirmed biopsy according to the 2016 World Health Organization (WHO)
classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed
or refractory disease.
• For indolent B-cell malignancies FL and CLL: Has histologically confirmed biopsy and
has relapsed or refractory disease after at least 2 prior systemic therapies and no
other available therapy.
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they
have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have
undetectable HBV viral load prior to randomization/allocation.
• Have an ECOG performance status of 0 to 2 assessed within 7 days before cycle 1 day 1.
Exclusion Criteria:
• Has received solid organ transplant at any time.
• Has clinically significant (ie, active) cardiovascular disease: cerebral vascular
accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months
prior to enrollment), unstable angina (<6 months prior to enrollment), congestive
heart failure (New York Heart Association Classification Class ≥II), or serious
cardiac arrhythmia requiring medication.
• Has pericardial effusion or clinically significant pleural effusion.
• Has ongoing Grade >1 peripheral neuropathy.
• Has a demyelinating form of Charcot-Marie-Tooth disease.
• Has a history of a second malignancy, unless potentially curative treatment has been
completed with no evidence of malignancy for 2 years.
• Participants with FL who have transformed to a more aggressive type of lymphoma.
• Has received prior systemic anticancer therapy within 5 half-lives or 4 weeks (if
prior therapy was a monoclonal antibodies) or 2 weeks (if prior therapy was small
molecules like kinase inhibitors) prior to the first dose of study intervention.
• Has received prior radiotherapy within 28 days of start of study intervention.
Participants must have recovered from all radiation-related toxicities.
• Has ongoing corticosteroid therapy exceeding 30 mg daily of prednisone equivalent.
• Has received a live or live-attenuated vaccine within 30 days before the first dose of
study intervention.
• Has known active central nervous system (CNS) lymphoma involvement or active CNS
involvement by lymphoma.
• Has an active infection requiring systemic therapy.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Active HBV or hepatitis C virus (HCV) infection.
• For Cohort C only: has any clinically significant gastrointestinal abnormalities that
might alter absorption.
MC1R-targeted Alpha-particle Therapy Trial in Adults With Advanced Melanoma
In this first-in human, phase I/IIa study, the safety and efficacy of [212Pb]VMT01, an
alpha-particle emitting therapeutic agent targeted to melanocortin sub-type 1 receptor (MC1R)
is being evaluated in patients with unresectable and metastatic melanoma.
Zachary Morris, MD
All
18 Years to 90 Years old
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05655312
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Inclusion Criteria:
• Ability to understand and willingness to provide informed consent, willingness to
comply with all study procedures for the duration of the study
• Male or female, aged ≥ 18 years
• Diagnosed with Stage IV metastatic melanoma, or unresectable Stage III
• Previously progressed (clinical or radiological progression) on at least one prior
therapy for metastatic melanoma
• Uptake of [68Ga]VMT02 or [203Pb]VMT01 by PET or SPECT imaging observed in at least one
melanoma tumor site using quantitative imaging analysis compared to reference normal
tissue
• Subjects on prior intravenous therapy (e.g., chemotherapy or checkpoint inhibitors),
or prior oral therapy (e.g., BRAF or MEK inhibitors) who demonstrate MC1R positivity
during screening are eligible for enrollment, provided that they undergo a wash-out
period of 21 days, or 14 days, respectively, prior to Day 1 treatment with
[212Pb]VMT01.
• Presence of measurable disease by RECIST v1.1 criteria assessed within 30 days prior
to the start of Day 1
• Ability to lie flat and still for up to two hours for imaging scans; moderate
conscious sedation allowed if indicated
• For females of reproductive potential: use of highly effective contraception for at
least one month prior to screening, and agreement to use such a method during study
participation and for an additional four weeks after the last administration of an
investigational product
• For males of reproductive potential: use of condoms or other methods to ensure
effective contraception with partner during study participation and for an additional
four weeks after the last administration of an investigational product
• ECOG performance score of < 2 at Screening
• Life expectancy of at least 3 months
• Evidence of sufficient organ function as determined by all of the following:
Oxygen saturation > 90% on room air eGFR > 50 mL/min/1.73m2 by CKD-EPI equation Complete
blood count with differential, within 7 calendar days prior to therapy and off Growth
Factors White blood cells (WBC) > 2500/mm3 Hemoglobin (Hgb) > 9.0 g/dL Platelets >
60,000/mm3 Absolute Neutrophil Count (ANC) > 1,250/mm3
The comprehensive metabolic panel, within seven calendar days prior to Day 1, demonstrating
values within the site's upper limit of normal (ULN), with the following exceptions:
Alanine aminotransferase (ALT) < 3x ULN Aspartate aminotransferase (AST) < 3x ULN Alkaline
phosphatase (ALP) < 2.5x ULN
Exclusion Criteria:
• Active secondary malignancy
• Prior treatment (for any reason) with radioactive nuclides; however, imaging tracers
are acceptable
• Pregnancy or breastfeeding a child
• Active infection
• Brain metastasis requiring acute therapy of any modality (i.e., surgical or external
beam radiotherapy) within two weeks of enrollment or clinical instability, including
signs or symptoms of brain edema. Subjects must demonstrate stable or decreasing brain
metastasis by a noninvasive imaging scan and must be off steroids or on decreasing
doses prior to enrollment.
• Treatment with another investigational drug product (therapeutic IND agents) within
the last 30 days.
• Current abuse of alcohol or illicit drugs
• Existence of any medical or social issues likely to interfere with study conductor
that may cause increased risk to the subject or to others, e.g., lack of ability to
follow radiation safety precautions
Melanoma, Skin, Melanoma/Skin cancer, Melanoma (Skin), Metastatic Melanoma, Melanoma Stage IV, Melanoma, Uveal, Mucosal Melanoma, Melanoma Stage III
Testing the Addition of Trastuzumab or Trastuzumab/Pertuzumab to the Usual Chemotherapy for HER2 Positive Endometrial Serous Carcinoma or Carcinosarcoma
This phase II/III trial tests whether adding trastuzumab and hyaluronidase-oysk (Herceptin
HylectaTM) or pertuzumab, trastuzumab and hyaluronidase-zzxf (PhesgoTM) to the usual
chemotherapy (paclitaxel and carboplatin) works to shrink tumors in patients with HER2
positive endometrial serous carcinoma or carcinosarcoma. Trastuzumab and pertuzumab are
monoclonal antibodies and forms of targeted therapy that attach to specific molecules
(receptors) on the surface of tumor cells, known as HER2 receptors. When trastuzumab or
pertuzumab attach to HER2 receptors, the signals that tell the cells to grow are blocked and
the tumor cell may be marked for destruction by the body's immune system. Hyaluronidase is an
endoglycosidase. It helps to keep pertuzumab and trastuzumab in the body longer, so that
these medications will have a greater effect. Hyaluronidase also allows trastuzumab and
trastuzumab/pertuzumab to be given by injection under the skin and shortens their
administration time compared to trastuzumab or pertuzumab alone. Paclitaxel is a taxane and
in a class of medications called antimicrotubule agents. It stops cancer cells from growing
and dividing and may kill them. Carboplatin is in a class of medications known as
platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin,
but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing
the growth of tumor cells. Giving Herceptin Hylecta or Phesgo in combination with paclitaxel
and carboplatin may shrink the tumor and prevent the cancer from coming back in patients with
HER2 positive endometrial serous carcinoma or carcinosarcoma.
Ellen Hartenbach, M.D.
Female
18 Years and over
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT05256225
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Inclusion Criteria:
• Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA-IVB, non-recurrent,
chemotherapy (chemo)-naive, HER2-positive endometrial serous carcinoma or endometrial
carcinosarcoma
• Histologic confirmation of the original primary tumor is required. Submission of
surgical pathology report (or endometrial biopsy pathology report in patients who
never undergo hysterectomy) is required
• Patients must be within 8 weeks of primary surgery (or endometrial biopsy in patients
who never undergo hysterectomy) at the time of study registration
• Patients may have measurable disease, non-measurable disease, or no measurable
disease. In patients with measurable disease, lesions will be defined and monitored by
RECIST v 1.1. Measurable disease is defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded). Each
lesion must be >= 10 mm when measured by computed tomography (CT) or magnetic
resonance imaging (MRI). Lymph nodes must be >= 15 mm in short axis when measured by
CT or MRI
• For patients with uterine-confined (stage I) disease, the tumor must be invasive into
the myometrium. Any amount of myoinvasion is acceptable for eligibility. Patients with
non-invasive disease, endometrial intraepithelial carcinoma alone, or disease confined
to a polyp will be excluded
• Additionally, patients must have the following histologic types to be eligible:
• Serous adenocarcinoma (may include =< 10% non-serous histology)
• Carcinosarcoma with serous epithelial component (only the serous component needs
to be HER2 positive; may include =< 10% non-serous histology)
• In cases where determination of serous is equivocal or challenging, aberrant p53
immunohistochemistry (IHC) (defined as overexpression of p53 compared to internal
controls) will be sufficient for inclusion
• All patients must have tumors that are HER2 positive as defined by American Society of
Clinical Oncology (ASCO)/College of American Pathologists (CAP) 2018 Breast Cancer
guidelines (https://documents.cap.org/documents/algorithim-evaluation-her2.pdf. In
general HER2 positivity is defined as any of the following:
• 3+ immunohistochemistry (IHC),
• 2+ IHC with positive in situ hybridization (ISH)
• Average HER2 copy number >= 6.0 signals/cell
• Average HER2 copy number >= 4.0 and < 6.0 signals/cell, with concurrent IHC 3+
• HER2/CEP17 ratio >= 4.0 signals/cell
• HER2/CEP 17 ratio >= 2.0 and < 4.0, with concurrent IHC 3+ IHC and ISH testing
will be done locally, at each participating institution and interpreted by local
pathologists. Alternatively, patients could be eligible if next generation
sequencing (NGS) demonstrates HER2 (ERBB2) amplification. NGS testing can be
performed through any designated labs as per the National Cancer Institute (NCI)
MATCH/NCI Combo-MATCH trial
(https://ecog-acrin.org/nci-match-eay131-designated-labs).
Pathology report showing results of institutional HER2 testing (or NGS testing results)
must be submitted.
Sites must submit all results available (IHC, ISH, and NGS)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Age >= 18
• Platelets >= 100,000/mcl (within 14 days prior to registration)
• Absolute neutrophil count (ANC) >= 1,500/mcl (within 14 days prior to registration)
• Creatinine =< 1.5 x institutional/laboratory upper limit of normal (ULN) or estimated
Glomerular filtration rate (eGFR) >= 50 mL/min using either the Cockcroft-Gault
equation, the Modification of Diet in Renal Disease Study, or as reported in the
comprehensive metabolic panel/basic metabolic panel (eGFR). (within 14 days prior to
registration)
• Total serum bilirubin level =< 1.5 x ULN (patients with known Gilbert's disease who
have bilirubin level =< 3 x ULN may be enrolled) (within 14 days prior to
registration)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (within
14 days prior to registration)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months of registration are eligible for
this trial
• Although the uterus will have been removed in the vast majority of patients, for
patients of child-bearing potential: negative urine or serum pregnancy test. If the
urine test is positive or cannot be confirmed as negative, a serum pregnancy test is
required. Patients will be considered of non-reproductive potential if they are
either:
• Postmenopausal (defined as at least 12 months with no menses without an
alternative medical cause; in women < 45 years of age, a high follicle
stimulating hormone [FSH] level in the postmenopausal range may be used to
confirm a postmenopausal state in women not using hormonal contraception or
hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single
FSH measurement is insufficient); OR
• Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or
bilateral tubal ligation/occlusion at least 6 weeks prior to registration
• Have a congenital or acquired condition that prevents childbearing
• 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. NOTE: Patients with prior
anthracycline exposure are NOT eligible
• Patients with evidence of chronic hepatitis B virus (HBV) infection must have an
undetectable HBV viral load 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 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:
• Prior Therapy:
• Patients must NOT have received prior chemotherapy, biologic therapy, or targeted
therapy for treatment of endometrial carcinoma
• Patients must NOT have received prior radiation therapy for treatment of
endometrial carcinoma. Prior radiation includes external beam pelvic radiation
therapy, external beam extended field pelvic/para-aortic radiation therapy,
and/or intravaginal brachytherapy
• NOTE: Vaginal brachytherapy for treatment of endometrial cancer is permitted
during study treatment. Planned use of vaginal brachytherapy must be
declared at time of registration
• Patients may have received prior hormonal therapy for treatment of endometrial
carcinoma. All hormonal therapy must be discontinued at least one week prior to
registration
• Patients may not have a planned interval cytoreduction or hysterectomy, prior to
documentation of progression, after study registration
• Patients may not have planned external beam radiotherapy, prior to documentation of
progression, after study registration
• Significant cardiovascular disease including:
• Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm
Hg despite antihypertensive medications
• Myocardial infarction or unstable angina within 6 months prior to registration
• New York Heart Association functional classification II, III or IV
• Serious cardiac arrhythmia requiring medication. This does not include
asymptomatic, atrial fibrillation with controlled ventricular rate
• Significant lung disease: dyspnea at rest grade 2 or greater (resulting from extensive
tumor involvement or other causes), pneumonitis grade 2 or greater, interstitial lung
disease grade 2 or greater, idiopathic pulmonary fibrosis, cystic fibrosis,
Aspergillosis, active tuberculosis, or history of opportunistic infections
(pneumocystis pneumonia or cytomegalovirus pneumonia)
• Patients with uncontrolled intercurrent illness including, but not limited to: ongoing
or active infection (except for uncomplicated urinary tract infection), uncontrolled
interstitial lung disease, symptomatic congestive heart failure, or psychiatric
illness/social situations that would limit compliance with study requirements
• Treatment with strong CYP2C8 or CYP3A4 inhibitors or inducers within 14 days or 5
drug-elimination half-lives, whichever is longer, prior to registration
• Women who are unwilling to discontinue nursing
Endometrial Serous Adenocarcinoma, Uterine Corpus Carcinosarcoma, Corpus Uteri, Uterus
A Trial of Robotic Versus Open Hysterectomy Surgery in Cervix Cancer (ROCC)
This is a randomized controlled trial to compare survival for patients who undergi robotic
assisted laparoscopy versus open radical hysterectomy and lymph node assessment for the
treatment of early stage cervical cancer.
Stephen Rose, MD
Female
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT04831580
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Inclusion Criteria:
1. Patient must have histologically confirmed adenocarcinoma (usual/classic/NOS),
squamous cell carcinoma, adenosquamous carcinoma (Including glassy cell)
2. Patient must be FIGO Stage IA2, IBI, IB2 (2018 staging) without evidence of definitive
parametrial, vaginal, nodal or distant metastases on exam or imaging. Patients with
tumor size less than or equal to 4 cm confirmed on MRI prior to randomization are
eligible.
3. Patient must have uterine size <12 cm AND felt to be appropriate for vaginal delivery
of the specimen per investigator.
4. Patient must be suitable surgical candidate with preoperative assessments such as labs
and EKG performed per institutional standard.
5. Patient must be age 18 years or older.
6. Patient must have ECOG performance status 0-1.
7. Patient must have a negative urine pregnancy test within 30 days of surgery in
pre-menopausal women.
8. Patient must have signed an approved informed consent and authorization permitting the
release of personal health information.
Exclusion Criteria:
1. Patients with any tumor histology other than those listed above, specifically
excluding the following histologies: neuroendocrine, other adenocarcinoma (gastric
type, endometrioid, clear cell, serous, signet ring, minimal deviation)
2. Patients with FIGO stage 1A1, IB3, II-IV (2018 staging).
3. Patient with inability to receive an MRI.
4. Patients with a tumor size greater than 4cm or on MRI confirmed prior to randomization
are excluded. Patients with definite evidence of vaginal/parametrial involvement on
MRI are excluded; if MRI findings are not definitive, then clinical examination must
also not reveal parametrial or vaginal extension).
5. Patients with evidence of metastatic disease (imaging or histologically positive lymph
nodes).
6. Patients with a history of prior pelvic or abdominal radiotherapy.
7. Patients with a prior malignancy < 5 years from enrollment with the exception of
non-melanoma skin cancer.
8. Patients who are unable to withstand prolonged lithotomy or steep trendelenberg.
9. Patient compliance and geographic proximity that do not allow adequate follow-up.
10. Patients with poorly controlled HIV with CD4 counts <500.
Phase 2 Study of DKN-01 in Colorectal Cancer (DeFianCe)
This is a Phase 2 randomized, open-label, two-part, multicenter study with a safety run-in to
evaluate efficacy and safety of DKN-01 plus FOLFIRI/FOLFOX and bevacizumab versus standard of
care (SOC) [FOLFIRI/FOLFOX and bevacizumab] as second-line treatment of advanced CRC
patients.
Dustin Deming, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05480306
Show full eligibility criteria
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Adult patients with advanced CRC with measurable disease (RECIST v1.1) who have
radiographically progressed during or following one line of systemic treatment will be
enrolled in the study.
Inclusion Criteria:
Patients meeting all of the following criteria will be considered eligible for study entry:
1. Disease progression following first-line systemic therapy with any
fluoropyrimidine-based regimen for advanced disease (except FOLFOXIRI, see exclusion
criteria).
• Patients may have received prior neoadjuvant or adjuvant therapy which could have
included irinotecan or oxaliplatin. If progression has occurred within 12 months from
last dose of neoadjuvant or adjuvant treatment, this regimen will be considered as the
one line of systemic therapy for advanced disease.
• If assigned to receive FOLFIRI, patient may have received no prior irinotecan as
part of first-line systemic therapy.
• If assigned to receive FOLFOX, patient may have received no prior oxaliplatin as
part of first line systemic therapy.
• Prior treatment with an anti-VEGF or anti-EGFR therapy is allowed as first-line
and/or maintenance systemic therapy.
2. Able to provide written informed consent for any study specific procedures.
3. One or more tumors measurable on radiographic imaging as defined by RECIST 1.1
4. Sufficient tumor tissue for mandatory pre-treatment evaluation (fresh biopsy
[preferred], or archived tissue block specimen).
5. ECOG performance status ≤1 within 7 days of first dose of study drug. Acceptable
liver, renal, hematologic, and coagulation function
6. Females of childbearing potential and male partners of female patients must agree to
use adequate contraception during the study and for 6 months after their last dose of
study drug
Exclusion Criteria:
Patients meeting any of the following criteria are not eligible for study entry:
1. Diagnosis of Microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR)
and/or BRAF V600E mutation positive colorectal cancer.
2. Prior therapy with an anti-DKK1, FOLFOXIRI, PD-1, anti-PD-L1, anti-PD-L-2 or any other
antibody or drug specifically targeting T-cell co-stimulation or coinhibitory
checkpoint.
3. Systemic anti-cancer therapy within 28 days prior to first dose of study drug.
4. Major surgery within 28 days prior to first dose of study drug.
5. Prior radiation therapy within 14 days prior to first dose of study drug.
6. Active leptomeningeal disease or uncontrolled brain metastases.
7. Any active cancer ≤ 2 years before first dose of study drug with the exception of
cancer for this study.
8. New York Heart Association Class III or IV cardiac disease, myocardial infarction
within the past 6 months, or unstable arrhythmia.
9. Fridericia-corrected QT interval (QTcF) > 470 msec (female) or history of congenital
long QT syndrome.
10. Active, uncontrolled bacterial, viral, or fungal infections, within 14 days of study
entry requiring systemic therapy.
11. Serious nonmalignant disease
12. Pregnant or nursing.
13. History of osteonecrosis of the hip or have evidence of structural bone abnormalities
in the proximal femur on MRI scan that are symptomatic and clinically significant.
14. Known osteoblastic bony metastasis.
15. Major surgery 28 days prior to study entry.
16. Prior radiation therapy within 14 days prior to study entry.
17. Significant allergy to a pharmaceutical therapy that, in the opinion of the
Investigator, poses an increased risk to the patient.
18. Active substance abuse.
19. Known dihydropyrimidine dehydrogenase deficiency.
20. Administration of a live vaccine within 28 days before first dose of study drug
Colorectal Cancer, Colorectal Adenocarcinoma, Colo-rectal Cancer, Colorectal Cancer Metastatic, Colon, Rectum, Colon and Rectum
A Phase 1 in Patients With HLA-A*0201+ and WT1+ Recurrent/Metastatic Cancers
This is a Phase 1, open-label, 2-part, multi-center study evaluating the safety,
tolerability, PK, pharmacodynamics (PD), immunogenicity, and antitumor activity of CUE-102
intravenous (IV) monotherapy in HLA-A*0201 positive patients with WT1 positive
recurrent/metastatic solid tumors who have failed conventional therapies.
Nataliya Uboha, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05360680
Show full eligibility criteria
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Inclusion Criteria:
1. Ability to provide informed consent and documentation of informed consent prior to
initiation of any study-related tests or procedures that are not part of standard of
care for the patient's disease.
2. Age ≥18 years old
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
4. Life expectancy ≥12 weeks
5. Measurable disease as per RECIST 1.1 and documented by CT and/or MRI.
6. All tumors must have histologically or cytologically confirmed cancer diagnosis
7. Patients must have any of the following cancers to be eligible:
A. Colorectal cancer
1. Histologically or cytologically documented adenocarcinoma of colon or rectum at
the time of initial presentation
2. Metastatic or locally advanced/unresectable disease
3. Documented disease progression after the last administration of standard
therapies or intolerance to at least 2 prior systemic treatment regimens (CUE-102
will be 3rd line therapy or greater).
B. Gastric cancer (including gastroesophageal junction)
1. Histologically or cytologically documented gastric cancer at the time of initial
presentation
2. Metastatic or locally advanced/unresectable disease
3. Documented disease progression after last administration of standard therapies or
intolerance to standard therapies. (CUE-102 will be 2nd line therapy or greater).
C. Pancreatic cancer
1. Histologically or cytologically documented pancreatic adenocarcinoma at the time
of initial presentation
2. Patients with metastatic or locally advanced/unresectable disease.
3. Prior systemic treatment must include either a fluoropyrimidine-based or
gemcitabine-based regimen in either the (neo)adjuvant or relapsed setting.
(CUE-102 will be 2nd line therapy or greater).
D. Ovarian cancer
1. Histologically or cytologically documented ovarian cancer at the time of initial
presentation
2. Metastatic or locally advanced/unresectable disease, with documented disease
progression after last administration of standard therapies or intolerance to
standard therapies.
3. Prior systemic treatment must include a platinum-based regimen. (CUE-102 will be
2nd line therapy or greater).
4. For patients determined to have platinum-sensitive disease, treatment with a
second platinum-based combination regimen +/- bevacizumab should be considered
prior to treatment with CUE-102 (CUE-102 will be 3rd line therapy or greater).
8. Patient must have HLA-A*0201 genotype as determined by genomic testing.
9. Patient must have histologically and/or cytologically proven tumor(s) that is WT1
positive.
10. Acceptable laboratory parameters.
11. Female patients of childbearing potential must agree to use acceptable contraceptive
measures from the time of main study consent through 90 days after discontinuation of
study drug administration.
12. Non-vasectomized male patients with partners of childbearing potential must use
barrier contraception from the time of main study consent through 90 days after
discontinuation of study drug.
13. Patients who have previously received an immune CPI (e.g., anti-programmed cell death
ligand 1 (anti PD-L1), anti-programmed cell death 1 (anti-PD-1), anti-cytotoxic T
lymphocyte-associated antigen 4 [CTLA-4]) prior to enrollment must have toxicities
related to the CPI resolved to CTCAE ≤ Grade 1 or baseline (level prior to the CPI) to
be eligible for enrollment. Patients who have experienced CPI-related endocrinopathies
(e.g., diabetes, adrenal insufficiency) may participate if endocrinopathies are
controlled (CTCAE ≤ Grade 1) with endocrinology support and appropriate repletion.
Note: Patients who experienced previous hypothyroidism toxicity on a CPI are eligible
to enter study regardless of CTCAE grade resolution as long as the patient is well
controlled on thyroid replacement hormone.
Exclusion Criteria:
1. Female patients who are pregnant or plan to become pregnant during the course of the
trial
2. Female patients who are breastfeeding
3. Patients with symptomatic central nervous system (CNS) metastases must have been
treated, be asymptomatic, and not have any of the following at the time of enrollment:
1. Need for concurrent treatment for the CNS disease (e.g., surgery, radiation,
corticosteroids >10 mg prednisone/day or equivalent)
2. Progression of CNS metastases on CT or MRI for at least 28 days after last day of
prior therapy for the CNS metastases
3. Concurrent leptomeningeal disease or cord compression.
4. Has an active autoimmune disease that has required systemic treatment in past 2 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 permitted.
5. History of prior allogeneic bone marrow, stem-cell, or solid organ transplantation
6. Treatment with any systemic anti-neoplastic therapy, or investigational therapy within
the 14 days (or 28 days, for antibody drugs), before the first dose of CUE-102.
7. Treatment with radiation therapy within 14 days before the first dose of CUE-102
8. Treatment with corticosteroids (> 10 mg per day prednisone or equivalent) or other
immune suppressive drugs within 14 days before the first dose of CUE-102. Steroids for
topical, ophthalmic, inhaled, or nasal administration are permitted. Physiological
replacement with up to a maximum dose of 5 mg equivalence of prednisone per day is
permitted.
9. History of clinically significant cardiovascular disease
10. Clinically significant pulmonary compromise (e.g., requirement for supplemental
oxygen)
11. Clinically significant gastrointestinal (GI) disorders
12. Patients who experienced the following immune CPI-related AEs are ineligible even if
the AE resolved to ≤ Grade 1 or baseline:
1. ≥ Grade 3 ocular AE
2. Changes in liver function tests that met the criteria for Hy's Law (> 3× ULN of
either ALT/AST with concurrent > 2× ULN of total bilirubin (total and direct) and
without alternate etiology)
3. ≥ Grade 3 neurologic toxicity
4. ≥ Grade 3 colitis
5. ≥ Grade 3 renal toxicity
13. Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral
treatment within 7 days before the first dose of CUE-102.
14. No known history of infection or positive test for HIV, Hepatitis B or Hepatitis C,
testing prior to enrollment is not required unless mandated by local authority
15. Second primary invasive malignancy that has not been in remission for > 2 years.
16. History of trauma or major surgery within 28 days before the first dose of CUE-102
17. Any serious underlying medical or psychiatric condition that would impair the ability
of the patient to receive or tolerate the planned treatment at the investigational
site
18. Known hypersensitivity to recombinant proteins, polysorbate 80 or any excipient
contained in the drug formulation for CUE-102
19. Vaccination with any live virus vaccine within 28 days before the first dose of
CUE-102. Inactivated annual influenza vaccination is allowed.
20. Dementia or altered mental status that would preclude understanding and rendering of
informed consent
21. Active or history of significant alcohol or other substance abuse within 1 year before
the first dose of CUE-102
Colorectal Cancer, Gastric Cancer, Pancreatic Cancer, Ovarian Cancer, Esophagus, Stomach, Colon, Pancreas, Other Digestive Organ, Ovary, Colon and Rectum, Gastrointestinal cancers, other
A Study of Tazemetostat With Rituximab and Abbreviated Bendamustine in the Frontline Treatment of High Tumor Burden Follicular Lymphoma
This study is planned as a single arm clinical trial of tazemetostat in combination with
bendamustine and rituximab with both a phase I and phase II component. All patients will
receive tazemetostat twice daily on days 1-28 in combination with bendamustine 90 mg/m2 IV on
days 1 and 2 and rituximab 375 mg/m2 IV on day 1 of a 28-day cycle for up to three cycles.
Following this, patients will receive tazemetostat twice daily on days 1-28 and rituximab 375
mg/m2 IV on day 1 of a 28-day cycle for up to three cycles.
Vaishalee Kenkre, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05551936
Show full eligibility criteria
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Inclusion Criteria:
• Written informed consent and HIPAA authorization for release of personal health
information. NOTE: HIPAA authorization may be included in the informed consent or
obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-2 within 10 days prior to registration.
• Low grade follicular lymphoma (grade 1-2 or 3A by WHO-HAEM4R and/or cFL by WHO-HAEM5).
Specifically, grade 3B or FLBL will not be allowed. Must not have evidence of
transformed lymphoma at the time of study enrollment.
• Stage II, III, or IV by Ann Arbor staging system.
• Meet the definition of high tumor burden follicular lymphoma as defined by Groupe
d'Etude des Lymphomes Follicularies (GELF) Criteria or be defined as high risk by the
follicular lymphoma international prognostic index (FLIPI) 1 or FLIPI 2.
--GELF Criteria (Must meet ≥ 1 of the following)
• Any nodal or extranodal mass ≥ 7 cm in diameter
• Involvement of ≥ 3 nodal sites ≥ 3 cm
• Systemic or B symptoms
• Presence of serous effusion
• Splenic enlargement
• Risk of compression syndrome (epidural, ureteral, etc)
• Leukemic phase of disease
• Cytopenia deemed due to disease involvement (hemoglobin < 10, granulocyte count <
1.5×10^9/L, or platelet count < 100×10^9/L)
• In addition to meeting GELF criteria, must have at least one FDG-avid site on PET that
measures 1.5 cm in at least one dimension of a nodal site or 1cm in at least one
dimension for extranodal sites.
• Received no prior therapy except local radiation therapy (field did not exceed 2
adjacent nodal regions), single agent rituximab (limited to 4 doses), or steroids for
symptom control in the 28 days preceding trial enrollment.
• Must have prior EZH2 testing already performed or have tissue available to perform
retrospective EZH2 testing. If prior EZH2 results are not available, tissue must be
submitted. Tissue block is preferred but unstained slides are also acceptable.
Patients who have insufficient or suboptimal tissue must be willing to have a biopsy
performed prior to starting study drugs. See Correlative Lab Manual for details.
• Demonstrate adequate organ function as defined below; all screening labs to be
obtained within 28 days prior to registration.
• Hematological
• Platelets ≥ 50 K/dL
• Absolute Neutrophil Count (ANC) ≥ 1000 K/mm3
• Hemoglobin (Hgb) ≥ 8 g/dL
• Renal
• Calculated creatinine clearance ≥ 40 mL/min using the Cockcroft-Gault
formula
• or Serum creatinine < 2 mg/dL
• Hepatic
• Bilirubin ≤ 1.5 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 3 × ULN
• Alanine aminotransferase (ALT) ≤ 3 × ULN
• Coagulation ---International Normalized Ratio (INR) or Prothrombin Time (PT)
Activated Partial Thromboplastin Time (aPTT) ≤ 2 × ULN
• Females of childbearing potential with a male partner able to father a child must have
a negative serum or urine pregnancy test within 7 days prior to registration. See the
protocol for definition of childbearing potential.
• Females of childbearing potential must be willing to abstain from vaginal intercourse
or use an effective method(s) of contraception from the time of informed consent,
during the study and for 6 months after the last dose of study drug(s). Males able to
father a child must be willing to abstain from vaginal intercourse or to use an
effective method(s) of contraception from initiation of treatment, during the study
and for 3 months after the last dose of study drug(s). See the protocol.
• As determined by the enrolling physician or protocol designee, ability of the subject
to understand and comply with study procedures for the entire length of the study.
Exclusion Criteria:
• Active infection requiring systemic therapy with 4 weeks of study drug administration.
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
mother is being treated on study).
• Concurrent malignancy or malignancy within the last 3 years (except for ductal breast
cancer in situ, non-melanoma skin cancer, prostate cancer not requiring treatment, and
cervical carcinoma in situ) whose natural history or treatment has the potential to
interfere with the safety or efficacy assessment of the investigational regimen are
not eligible for this trial.
• Active central nervous system (CNS) metastases or leptomeningeal disease. NOTE:
Subjects who are symptomatic and have not undergone prior brain imaging must undergo a
head computed tomography (CT) scan or brain MRI within 28 days prior to registration
to exclude brain metastases.
• Treatment with any investigational drug within 4 weeks prior to registration.
• Subjects who require chronic use of moderate or strong CYP3A4/5 inhibitors or inducers
within 28 days prior to registration.
• Clinically significant acute infection requiring systemic antibacterial, antifungal,
or antiviral therapy.
• Known Uncontrolled Human Immunodeficiency Virus infection. Testing not required. NOTE:
If a subject is known to have HIV/AIDS, then they will be allowed on study with
adequate antiviral therapy, no detectable viral load, and stable on antiviral
treatment for ≥ 4 weeks prior to first dose of study drug(s).
• Known hepatitis C infection. Testing not required. NOTE: If hepatitis C antibody test
is known positive, patients are excluded unless a hepatitis C virus ribonucleic acid
(HCV RNA) is negative.
• Must be tested for hepatitis B within 28 days of registration: including hepatitis B
surface antigen, hepatitis B surface antibody, hepatitis B core antibody. A positive
hepatitis B core antibody should be followed by hepatitis B DNA PCR testing to confirm
or rule out active infection. Patients with hepatitis B surface antigen and/or
detectable hepatitis B DNA PCR are not allowed on study. Patients with a positive
hepatitis B core antibody but negative hepatitis B surface antigen and hepatitis B DNA
PCR will be allowed on study, but hepatitis B prophylactic treatment should be
strongly considered.
• Clinically significant cardiovascular disease or cardiac insufficiency (New York Heart
Association classes III-IV), cardiomyopathy, preexisting clinically significant
arrhythmia, acute myocardial infarction within 3 months of enrollment, angina pectoris
within 3 months of enrollment.
This Study Aims to Find the Best Dose of BI 907828 (Brigimadlin) in Patients With Different Types of Advanced Cancer (Solid Tumors)
This study is open to adults with different types of advanced cancer (solid tumors). The
purpose of this study is to find out the most suitable dose of BI 907828 (brigimadlin) the
participants can tolerate. The most suitable dose is used in the second part to find out
whether brigimadlin makes tumors shrink.
In this study, brigimadlin is given to humans for the first time. Brigimadlin is a so-called
MDM2 inhibitor that is being developed to treat cancer. Brigimadlin is taken as a tablet.
Participants either take a dose of brigimadlin on one day every 3 weeks or on two days every
4 weeks.
The participants are in the study for as long as they benefit from and can tolerate
treatment. The doctors regularly check the participants' general health during the study.
Jeremy Kratz, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT03449381
Show full eligibility criteria
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Inclusion Criteria:
• Provision of signed and dated, written informed consent form ICF in accordance with
ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or
analyses.
• Pathologically documented, advanced solid tumors.
• Patients fulfilling one or more of the following criteria:
• Radiologically documented disease progression or relapse
• Patients who are not eligible to receive standard of care treatments, and for
whom no proven treatments exist.
• Patients with MDM2 amplified sarcomas who require first line treatment (for Ph
Ib/dose expansion •Cohort 1 only).
• Patients with MDM2 amplified sarcomas may fulfil any one of the above three criteria
to be considered eligible.
• Phase Ia (dose escalation) only:
• Patient has a tumor with either a known TP53 wild type status, or unknown TP53 status,
and regardless of MDM2 amplification status, at the time of study entry.
• Phase Ib (expansion phase) only:
• Cohort 1: TP53 wt and MDM2-amplified sarcoma with advanced/metastatic disease at any
line of therapy. If TP53 status is not available during screening, the patient may be
included with unknown TP53 status if a tissue sample is submitted for central
laboratory assessment. If TP53 status cannot be evaluated, the patient may be included
if agreed between the Investigator and Sponsor.
• Cohort 2: TP53 wt and MDM2- amplified NSCLC, urothelial, gastric, biliary tract
(including cholangiocarcinoma, intra- and extrahepatic biliary tree, gall blander and
ampulla of vater) or pancreatic solidPDAC tumors who have had at least one previous
line of therapy for advanced/metastatic disease. If TP53 status cannot be evaluated
the patient may be included if agreed between the Investigator and Sponsor
• Phase Ia (dose escalation) only:
• Patient with either measurable or non-measurable disease.
• Non-evaluable disease allowed.
• Phase Ib (expansion phase) only:
• At least one target lesion that can be accurately measured per RECIST v.1.1.
• Phase Ia:
• Patient must be willing to undergo blood sampling for PK, pharmacodynamic, biomarker,
and PGx analyses.
• Phase Ib:
• Patient must be willing to undergo tumor biopsy sampling for pharmacodynamic analyses
and blood sampling for PK, pharmacodynamics, and biomarker analyses.
• Willingness to provide a fresh tumor tissue sample obtained after relapse/ progression
during or after prior therapy. In case a fresh biopsy cannot be obtained (e.g.
inaccessible lesions or patient safety concern), an archived specimen, collected
before screening within 12 months of enrollment, may be submitted. If these
requirements cannot be met, then the patient may be allowed to enter the study at
Sponsor discretion, after agreement between the Investigator and Sponsor.
• Further inclusion criteria apply
Exclusion Criteria:
• Previous administration of BI 907828 (brigimadlin) or any other MDM2-p53 or MDMX
(MDM4)-p53 antagonist.
• Known TP53 mutant tumor.
• Symptomatic metastases from non-brain tumors. Note: Patients with previously treated
brain metastases may participate provided they are stable, without evidence of
progression by imaging (using the identical imaging modality for each assessment,
either MRI or computed tomography (CT) scan), for at least four weeks prior to the
first dose of trial treatment, and any neurologic symptoms have returned to baseline;
have no evidence of new or enlarging brain metastases. Patients on corticosteroids
must have a stable dose for at least 5 days prior to baseline MRI.
• Patients with history of bleeding diathesis.
• Major surgery (major according to the Investigator's assessment) performed within 12
weeks prior to start of study treatment, or planned within 12 months after screening
(e.g. hip replacement).
• Any other documented active or suspected malignancy or history of malignancy within 3
years prior to screening, except appropriately treated basal cell carcinoma of the
skin or in situ carcinoma of uterine cervix, or other local tumors considered cured by
local treatment.
• Patients who must or wish to continue the intake of restricted medications or any drug
considered likely to interfere with the safe conduct of the trial.
• Further exclusion criteria apply.
Neoplasms, 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, Unknown Sites, Ill-Defined Sites, Any Site, 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
Safety and Efficacy of IMC-F106C as a Single Agent and in Combination With Checkpoint Inhibitors
IMC-F106C is an immune-mobilizing monoclonal T cell receptor against cancer (ImmTAC ®)
designed for the treatment of cancers positive for the tumor-associated antigen PRAME. This
is a first-in-human trial designed to evaluate the safety and efficacy of IMC-F106C in adult
patients who have the appropriate HLA-A2 tissue marker and whose cancer is positive for
PRAME.
Vincent Ma, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04262466
Show full eligibility criteria
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Inclusion Criteria:
1. ECOG PS 0 or 1
2. HLA-A*02:01 positive
3. PRAME positive tumor
4. Relapsed from, refractory to, or intolerant of standard therapies; or, in combination
with standard therapies
5. If applicable, must agree to use highly effective contraception
Exclusion Criteria:
1. Symptomatic or untreated central nervous system metastasis
2. Recent bowel obstruction
3. Ongoing ascites or effusion requiring recent drainages
4. Significant immune-mediated adverse event with prior immunotherapy (patients in
checkpoint inhibitor combination treatment)
5. Inadequate washout from prior anticancer therapy
6. Significant ongoing toxicity from prior anticancer treatment
7. Out-of-range laboratory values
8. Clinically significant lung, heart, or autoimmune disease
9. Ongoing requirement for immunosuppressive treatment
10. Prior solid organ or bone marrow transplant
11. Active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency
virus (HIV) infection
12. Significant secondary malignancy
13. Hypersensitivity to study drug or excipients
14. Antibiotics, vaccines or surgery within 2-4 weeks prior to the first dose of study
intervention
15. Pregnant or lactating
16. Any other contraindication for applicable combination partner based on local
prescribing information
Testing the Safety and Tolerability of the Anti-cancer Drugs Trastuzumab Deruxtecan and Neratinib for Cancers With Changes in the HER2 Gene
This phase I trial tests the safety, side effects, and best dose of neratinib in combination
with trastuzumab deruxtecan in treating patients with solid tumors that have spread to other
parts of the body (metastatic) or that cannot be removed by surgery (unresectable), and have
changes in a gene called human epidermal growth factor receptor 2 (HER2). Neratinib is in a
class of medications called kinase inhibitors. It works by blocking the action of an abnormal
protein that signals tumor cells to multiply. This helps slow or stop the spread of tumor
cells. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates.
It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug,
called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and
delivers deruxtecan to kill them. Adding neratinib to trastuzumab deruxtecan may be able to
shrink cancer with a change in the HER2 gene.
Nataliya Uboha, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05372614
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patients must have histologically confirmed malignancy that is metastatic or
unresectable with participation in this clinical trial determined to be the best
option for next treatment in the opinion of the investigator
• Patients must have a solid tumor with HER2-positivity as determined by any one or more
of the following:
• HER2 overexpression defined by IHC 3+
• ERBB2 amplification by ISH or next-generation sequencing as determined by any
CLIA certified lab
• A known HER2 activating mutation
• HER2 overexpression by IHC/ISH will follow histology specific ASCO-CAP guidelines
for breast and gastric cancers. For tumor histologies without specific guidelines
the following criteria will apply:
• HER2 IHC should be performed first, followed by ISH methods in cases showing
2+ (equivocal) expression by IHC. Positive (IHC 3+) or negative (IHC 0 or
1+) do not require further ISH testing. Cases with HER2:CEP17 ratio ≥2 or an
average HER2 copy number ≥6.0 signals per cell are considered positive by
ISH
• Known HER2 activating mutations:
• G309A/E
• S310F/Y
• S653C
• V659E
• G660D
• R678Q
• E693K
• Q709L
• L755S/P
• Del. 755-759
• D769Y/H
• G776V/C
• V777L
• V842I
• T862A
• L869R
• H878Y
• All exon 20 insertions, including:
• A771_Y772insYVMA
• A775_G776insYVMA
• Y772_A775dup
• P780_Y781insGSP
• G778_P780dup
• V697L
• T733I
• D769N
• L841V
• L866M
• R896C
• If a different mutation is identified, contact the study chair for conferral.
Synonymous mutations are not eligible
• Patients must have received at least 1 prior line of therapy in the
advanced/metastatic setting. No limitation on number of prior therapies; however,
patients may not have received neratinib or DS-8201a previously. Prior HER2-targeted
therapy other than neratinib or DS-8201a is allowed (e.g., trastuzumab, pertuzumab,
TDM-1, lapatinib, etc.)
• Age >= 18 years. Because no dosing or adverse event data are currently available on
the use of neratinib in combination with DS-8201a in patients < 18 years of age,
children are excluded from this study
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1
(Karnofsky >= 70%)
• Hemoglobin >= 9.0 g/dL (>= 8.0 g/dL for gastric cancer [GC] only) (within 14 days of
enrollment)
• No transfusions with red blood cells or platelets are allowed within 1 week prior
to screening assessment
• Serum albumin >= 2.5 g/dL (within 14 days of enrollment)
• Leukocytes >= 3.0 K/cumm (within 14 days of enrollment)
• Absolute neutrophil count >= 1.5 K/cumm (within 14 days of enrollment)
• No administration of granulocyte colony-stimulating factor (G-CSF) is allowed
within 1 week prior to screening assessment
• Platelets >= 100 K/cumm (within 14 days of enrollment)
• No transfusions with red blood cells or platelets are allowed within 1 week prior
to screening assessment
• Total bilirubin =< 1.5 × institutional upper limit of normal (ULN), (< 3 × ULN in the
presence of documented Gilbert's syndrome or liver metastases at baseline) (within 14
days of enrollment)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 3 x ULN (if liver metastases are present =< 5 x ULN) (within 14 days of enrollment)
• International normalized ratio (INR)/prothrombin time (PT) and activated partial
thromboplastin time (aPTT) =< 1.5 x institutional ULN (within 14 days of enrollment)
• This applies only to patients who are not receiving therapeutic anticoagulation
that may affect INR. Those who are on therapeutic anticoagulation, should be on a
stable dose for 4 weeks and should be considered within therapeutic range
• Creatinine =< 1.5 x institutional ULN OR Glomerular filtration rate (GFR) >= 30
mL/min/1.73 m^2 (using the Cockcroft-Gault equation) (within 14 days of enrollment)
• Patients who are human immunodeficiency virus (HIV)-positive may participate IF they
meet the following eligibility requirements:
• They must be stable on their anti-retroviral regimen, and they must be healthy
from an HIV perspective
• They must have a CD4 count of greater than 250 cells/mcL over the past 6 months
on this same anti-retroviral regimen and must not have had a CD4 count < 200
cells/ul over the past 2 years, unless it was deemed related to THE CANCER AND/OR
CHEMOTHERAPY-induced bone marrow suppression
• For patients who have received chemotherapy in the past 6 months, a CD4
count < 250 cells/ul during chemotherapy is permitted as long as viral loads
were undetectable during this same chemotherapy
• They must have an undetectable viral load and a CD4 count >= 250 cells/uL within
7 days of enrollment
• They must not be currently receiving prophylactic therapy for an opportunistic
infection and must not have had an opportunistic infection within the past 6
months HIV-infected patients should be monitored every 12 weeks for viral load
and CD4 counts
• 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 the following criteria are met:
1) follow-up brain imaging done at least in 4 weeks after central nervous system
(CNS)-directed therapy shows no evidence of progression and 2) the patient no longer
requires steroids, or is on a stable steroid dose > 4 weeks
• Patients with radiographically new or progressive brain metastases (active brain
metastases) or leptomeningeal disease are eligible only if has no progressive clinical
symptoms and if the treating physician determines that immediate CNS specific
treatment is not required and is unlikely to be required during the first cycle of
therapy
• Patients should be New York Heart Association functional classification of class 2B or
better
• Patients must have left ventricular ejection fraction (LVEF) >= 50% by either an
echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before
randomization/enrollment
• Dose expansion phase (PD cohort): Patients must have disease that is evaluable or
measurable by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Dose expansion phase (PD cohort): Patients must have at least one lesion suitable for
biopsy without significant risk to the patient. The biopsiable lesion can be the same
as the evaluable lesion for response by RECIST 1.1
• Patients who had clinically significant side effects from prior cancer therapy must
have recovered to grade 1 or below
• HER2 antibody conjugated to a topoisomerase 1 inhibitor agents as well as other
therapeutic agents used in this trial are known to be teratogenic; thus, women of
child-bearing potential and men must agree to use adequate contraception (hormonal or
barrier method of birth control; abstinence) prior to study entry, for the duration of
study participation, and for at least 1 month after the last dose of neratinib, or at
least 7 months after the last dose of DS-8201a, whichever is longer (women of
childbearing potential [WOCBP] only). 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. Men treated or enrolled on this protocol must also
agree to use adequate contraception prior to the study, for the duration of study
participation, and 3 months after the last dose of neratinib, or 4 months after
completion of DS-8021a administration, whichever is longer
• Women of non-child-bearing potential defined as pre-menopausal females with a
documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of
spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous
follicle-stimulating hormone [FSH] > 40 mIU/mL and estradiol < 40 pg/mL [< 147 pmol/L]
is confirmatory) are eligible. Females on hormone replacement therapy (HRT) and whose
menopausal status is in doubt will be required to use one of the contraception methods
outlined for women of child-bearing potential if they wish to continue their HRT
during the study. Otherwise, they must discontinue HRT to allow confirmation of
post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4
weeks will elapse between the cessation of therapy and the blood draw; this interval
depends on the type and dosage of HRT. Following confirmation of their post-menopausal
status, they can resume use of HRT during the study without use of a contraceptive
method
• Male subjects must not freeze or donate sperm starting at screening and throughout the
study period, and at least 4 months after the final study drug administration.
Preservation of sperm should be considered prior to enrollment in this study
• Female subjects must not donate, or retrieve for their own use, ova from the time of
screening and throughout the study treatment period, and for at least 7 months after
the final study drug administration
• Ability to understand and the willingness to sign a written informed consent document.
Participants with impaired decision-making capacity who have a legally-authorized
representative (LAR) and/or family member available will also be eligible
Exclusion Criteria:
• With the exception of medications that are under investigation in the study (e.g.,
standard of care, comparators, or combination therapies), the following medications,
treatment, and procedures will be prohibited during the treatment period. The sponsor
must be notified if a subject receives any of these during the study:
• Other anticancer therapy, including small-molecule targeted agents within 2 weeks
or five half-lives, whichever is longer; chemotherapy otherwise not specified
(including, but not limited to cytotoxic chemotherapy, antibody drug conjugates,
retinoid therapy, hormonal therapy) within 3 weeks; immunotherapy or monoclonal
antibody within 4 weeks; and nitrosureas or mitomycin C within 6 weeks
(concurrent use of hormones for noncancer-related conditions [e.g., insulin for
diabetes and hormone replacement therapy] is acceptable)
• Other investigational therapeutic agents
• Patients who have had major surgery or radiation within 4 weeks; palliative
stereotactic radiation within 2 weeks (except for palliative radiation to known
metastatic sites as long as it does not affect assessment of response or
interrupt treatment for more than the maximum time specified in dose modification
section)
• Radiotherapy to the thorax (palliative radiation to known metastatic sites in the
thoracic spine is permitted in this study)
• Concomitant use of chronic systemic (IV or oral) corticosteroids or other
immunosuppressive medications except for managing adverse events (inhaled
steroids or intra-articular steroid injections are permitted in this study);
chronic replacement dose steroids (e.g., for those with adrenal insufficiency)
are permitted in this study
• Subjects with bronchopulmonary disorders who require intermittent use of
bronchodilators (such as albuterol) will not be excluded from this study
• Concomitant treatment with chloroquine or hydroxychloroquine is not allowed
during the study treatment due to concern for overlapping toxicities. If
treatment with chloroquine and hydroxychloroquine treatment is absolutely
required, study treatment must be interrupted. If chloroquine or
hydroxychloroquine is administered, then a wash-out period of more than 14 days
is required before restarting study treatment
• Patients with a history of (non-infectious) interstitial lung disease
(ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where
suspected ILD/pneumonitis cannot be ruled out by imaging at screening
• Patients with clinically severe pulmonary compromise resulting from intercurrent
pulmonary illnesses including, but not limited to, any underlying pulmonary disorder
(i.e. pulmonary emboli within three months of the study enrollment, severe asthma,
severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural
effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with
potential pulmonary involvement (i.e. rheumatoid arthritis, Sjogren's, sarcoidosis,
etc.), or prior pneumonectomy
• Patients with history of allergic reactions attributed to compounds of similar
chemical or biologic composition to DS-8201a, the inactive ingredients in the drug
product, or neratinib
• Patients who have a history of severe hypersensitivity reactions to other monoclonal
antibodies
• Patients receiving any medications or substances that are moderate or strong
inhibitors or inducers of CYP3A4 and P-glycoprotein are ineligible. Avoid concomitant
use with proton pump inhibitors and P-glycoprotein substrates. 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
• Patients with a medical history of myocardial infarction within 6 months before
enrollment, or symptomatic congestive heart failure (CHF) (New York Heart Association
class II to IV)
• Patients with a corrected QT interval (QTc) prolongation to > 470 ms (females) or >
450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram
(ECG)
• Patients with clinically significant corneal disease in the opinion of the
investigator
• Patients with a pleural effusion, ascites, or pericardial effusion that requires
drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy
(CART). (Drainage and CART are not allowed within 2 weeks prior to screening
assessment) (GC indication)
• Patients with spinal cord compression
• Patients with an uncontrolled infection requiring IV antibiotics, antivirals, or
antifungals
• Patients with unresolved toxicities from previous anticancer therapy, defined as
toxicities (other than alopecia) not yet resolved to grade =< 1 or baseline. Subjects
with chronic grade 2 toxicities may be eligible per the discretion of the investigator
after consultation with the sponsor medical monitor or designee (e.g., grade 2
chemotherapy-induced neuropathy)
• Patients with substance abuse or any other medical conditions such as clinically
significant cardiac or psychological conditions, that may, in the opinion of the
investigator, interfere with the subject's participation in the clinical study or
evaluation of the clinical study results
• Pregnant women are excluded from this study because DS-8201a is a HER2 antibody
conjugated to a topoisomerase 1 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 DS-8201a,
breastfeeding should be discontinued if the mother is treated with DS-8201a. These
potential risks may also apply to other agents used in this study
• Prior treatment with neratinib or DS-8201a
• Clinically significant chronic gastrointestinal disorder with diarrhea as a major
symptom; G2 or greater diarrhea at baseline. Please contact the study PI for any
patient with more than two episodes of diarrhea per day averaged over at least a 7 day
period at time of screening to determine whether the diarrhea would be considered
clinically significant
• Inability to swallow tablets
• Patients with active additional malignancy or a personal history of additional
malignancy that may affect outcome of disease under treatment (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 at the discretion of the treating investigator are allowed)
• Patients with prior allogeneic organ transplantation including allogeneic stem cell
transplantation
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, Unknown Sites, Ill-Defined Sites, Any Site, 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, Malignant Solid Neoplasm
Treating Prostate Cancer That Has Come Back After Surgery With Apalutamide and Targeted Radiation Based on PET Imaging
This phase III trial tests two questions by two separate comparisons of therapies. The first
question is whether enhanced therapy (apalutamide in combination with abiraterone +
prednisone) added to standard of care (prostate radiation therapy and short term androgen
deprivation) is more effective compared to standard of care alone in patients with prostate
cancer who experience biochemical recurrence (a rise in the blood level of prostate specific
antigen [PSA] after surgical removal of the prostate cancer).
A second question tests treatment in patients with biochemical recurrence who show prostate
cancer spreading outside the pelvis (metastasis) by positron emission tomography (PET)
imaging. In these patients, the benefit of adding metastasis-directed radiation to enhanced
therapy (apalutamide in combination with abiraterone + prednisone) is tested.
Diagnostic procedures, such as PET, may help doctors look for cancer that has spread to the
pelvis. Androgens are hormones that may cause the growth of prostate cancer cells.
Apalutamide may help fight prostate cancer by blocking the use of androgens by the tumor
cells. Metastasis-directed targeted radiation therapy uses high energy rays to kill tumor
cells and shrink tumors that have spread. This trial may help doctors determine if using PET
results to deliver more tailored treatment (i.e., adding apalutamide, with or without
targeted radiation therapy, to standard of care treatment) works better than standard of care
treatment alone in patients with biochemical recurrence of prostate cancer.
John Floberg, Assistant Professor
Male
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04423211
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Inclusion Criteria:
• STEP 0: REGISTRATION ELIGIBILITY CRITERIA
• Patient must be male and >= 18 years of age.
• Patient must have had a radical prostatectomy (RP) as definitive therapy for
histopathologically-proven prostatic adenocarcinoma
• Patient must have biochemical recurrence (BCR) after RP, defined as follows:
• If time to BCR, defined as time to first detectable PSA ( > lower limit of normal
for assay used) after RP, is < 12 months, a minimum PSA level of >= 0.2 ng/mL and
a confirmatory reading of >= 0.2 ng/mL is required, per the American Urological
Association (AUA) definition (Note: patients with a persistent PSA reading of at
least 0.2 ng/mL are eligible)
• If time to BCR, defined as time to first detectable PSA (> lower limit of normal
for assay used) after RP, is >= 12 months, a minimum absolute PSA of 0.5 ng/mL is
required
• If the patient has a detectable PSA (> lower limit of normal for assay used) at
any time after RP AND has an eligible baseline SOC PET (PET1) with at least one
positive lesion in any location, then there is no minimum PSA requirement
• Patients must have no definite evidence for extrapelvic metastatic disease by
conventional imaging modalities (CIM) (CT abdomen/pelvis or MRI abdomen/pelvis AND
bone scintigraphy, or equivalent), within 26 weeks prior to Step 0 registration. If a
patient only has a study-eligible PET/CT or PET/MR (i.e., PET done without prior CIM):
if the PET is negative for extrapelvic lesions, then baseline CIM is NOT required. If
the PET positive for extrapelvic lesions, then patient should have a baseline CT/MRI
for soft tissue lesions and/or a bone scan for osseous lesions
• Study eligible = PET using FDA-approved radiotracer and performed within 16 weeks
prior to study registration
• Extra-pelvic metastases is defined as any osseous metastases and/or any extrapelvic
soft tissue, lymph nodes and organ metastases; extra-pelvic is defined as superior to
common iliac bifurcation, outside of standard prostate bed + whole pelvis nodal RT
fields. Baseline PET/CT or PET/MR scan (PET1) is eligible for this study if the SOC
PET scan is completed with an FDA approved radiotracer for prostate cancer after Step
0 registration and prior to Step 1 randomization OR up to 16 weeks prior to Step 0
registration
• Patient must be a candidate for SOC post-prostatectomy radiation therapy (RT) to the
prostate bed and pelvic nodes with androgen deprivation therapy (ADT)
• Patient must have the ability to understand and the willingness to sign a written
informed consent document. Patients with impaired decision-making capacity (IDMC) who
have a legally authorized representative (LAR) or caregiver and/or family member
available will also be considered eligible
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Patient must not have started ADT for biochemical recurrence prior to baseline PET
(PET1) imaging. A short course of low-dose anti-androgen such as bicalutamide, given
after baseline study PET/CT but prior to study registration, is permitted as a brief
temporizing measure in advance of starting protocol-approved SOC ADT.
• Patient must not be enrolled in another therapeutic clinical trial
• Patient must be able to lie flat and still for approximately 20-30 minutes or
otherwise tolerate a PET scan and radiation treatment planning and delivery
• Patients undergoing a PET/MR must meet local institutional safety guidelines for MRI
• Patient must not have history of seizures or known condition that may cause
predisposal to seizures (e.g., stroke or head trauma resulting in loss of
consciousness) within 1 year prior to registration
• Patient must not have history of inflammatory bowel disease or any gastrointestinal
disorder affecting absorption that is expected to increase risk of complication from
radiotherapy
• Hemoglobin (Hgb) >= 9.0 g/dL (independent of transfusion and/or growth factors within
3 months prior to Step 0 registration) (obtained within 8 weeks prior to Step 0
registration)
• Leukocytes >= 3,000/mcL (obtained within 8 weeks prior to Step 0 registration)
• Absolute neutrophil count >= 1,500/mcL (obtained within 8 weeks prior to Step 0
registration)
• Platelets >= 100,000/mcL (obtained within 8 weeks prior to Step 0 registration)
• Total bilirubin < 1.5 x institutional upper limit of normal (ULN) (patients with
Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, must have a direct bilirubin of
< 1.5 x ULN to be eligible) (obtained within 8 weeks prior to Step 0 registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x institutional ULN (obtained within 8 weeks prior to Step 0 registration)
• Creatine < 1.5 x instituional ULN (or measured 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
• 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 I or II (by patient symptoms) or A
or B (by objective assessment)
• Patient must not have completed a course of prior pelvic radiation therapy for any
reason
• Patient must agree not to father children while on study
• Patient must be English or Spanish speaking to be eligible for the QOL component of
the study
• NOTE: Sites cannot translate the associated QOL forms
• STEP 1: RANDOMIZATION ELIGIBILITY CRITERIA
• Patient must have completed a baseline SOC PET/CT or PET/MR (PET1 scan) using FDA
approved radiotracer with results of extra-pelvic metastases involvement known
(positive or negative). The PET1 must have been completed after Step 0 registration
and prior to Step 1 randomization OR up to 12 weeks prior to Step 0 registration
• For patients with negative extra-pelvic metastases, PET-imaging status of intra-pelvic
nodes must be known (positive or negative)
• For patients with positive extra-pelvic metastases (defined as any PET positive
lesions outside of standard salvage RT fields [prostate bed +/- typical whole
pelvis]), the number of extra-pelvic lesions must be known (1 •5 or > 5 extra-pelvic
lesions)
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
This study collects blood and tissue samples from patients with cancer and without cancer to
evaluate tests for early cancer detection. Collecting and storing samples of blood and tissue
from patients with and without cancer to study in the laboratory may help researchers develop
tests for the early detection of cancers.
David Kosoff, MD
All
40 Years to 75 Years old
N/A
This study is also accepting healthy volunteers
NCT05334069
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Inclusion Criteria:
• Participants with a cancer diagnosis: Documentation of disease:
• Histologic documentation: Histologically confirmed diagnosis of invasive cancer
• Stage: Stage I-IV per American Joint Committee on Cancer (AJCC) 7th edition, with
the exception of patients with leukemia, lymphoma, and multiple myeloma
• For leukemia: Type (chronic lymphocytic leukemia [CLL], chronic myeloid
leukemia [CML], acute lymphoblastic lymphoma [ALL], acute myeloid leukemia
[AML])
• For lymphoma: Stage I-IV based on Ann Arbor staging
• For multiple myeloma: Stage I, II, III based on Revised International
Staging System (RISS)
• One of the following tumor types:
• Colorectal
• Bladder
• Head and neck
• Hepatobiliary
• Lung
• Lymphoma
• Leukemia
• Ovary *** For these specific cancer types only, patients may be enrolled
prior to histologic confirmation of malignancy. Sites are required to
contact the study chairs to review appropriateness for enrollment
• Pancreas *** For these specific cancer types only, patients may be enrolled
prior to histologic confirmation of malignancy. Sites are required to
contact the study chairs to review appropriateness for enrollment
• Multiple myeloma
• Gastric, esophageal or gastroesophageal
• Breast
• Thyroid
• Kidney
• For these specific cancer types only, patients may be enrolled prior to
histologic confirmation of malignancy. Sites are required to contact
the study chairs to review appropriateness for enrollment
• Endometrium
• Prostate
• Melanoma
*** For these specific cancer types only, patients may be enrolled prior to
histologic confirmation of malignancy. Sites are required to contact the
study chairs to review appropriateness for enrollment
• Sarcoma
• Participants with a cancer diagnosis: No prior definitive systemic or local
anti-cancer intervention
• Participants with a cancer diagnosis: Age >= 40 and =< 75
• Participants with a cancer diagnosis: No known current pregnancy by self-report
• Participants with a cancer diagnosis: No known or prior history of in situ or invasive
malignancy (excluding in situ non-melanoma skin cancers) other than the current cancer
diagnosis
• Participants with a cancer diagnosis: Willingness to provide blood samples for
research use
• Participants with a cancer diagnosis: Absence of medical contraindications to a
research blood draw volume of 60 mL
• Participants with a cancer diagnosis: No history of organ transplantation
• Participants with a cancer diagnosis: Ability to read and comprehend English or
Spanish
* Eligibility is restricted to individuals who can comprehend and read English or
Spanish given that participation in the study will require the ability to read and
complete questionnaires that are available only in those two languages
• Participants without a cancer diagnosis and without suspicion of cancer: Age >= 40 and
=< 75
• Participants without a cancer diagnosis and without suspicion of cancer: No known
current pregnancy by self-report
• Participants without a cancer diagnosis and without suspicion of cancer: No known or
prior history of in situ or invasive malignancy (excluding in situ non-melanoma skin
cancers)
• Participants without a cancer diagnosis and without suspicion of cancer: Willingness
to provide blood samples for research use
• Participants without a cancer diagnosis and without suspicion of cancer: Absence of
medical contraindications to a research blood draw volume of 60 mL
• Participants without a cancer diagnosis and without suspicion of cancer: No history of
organ transplantation
• Participants without a cancer diagnosis and without suspicion of cancer: Ability to
read and comprehend English or Spanish
* Eligibility is restricted to individuals who can comprehend and read English or
Spanish given that participation in the study will require the ability to read and
complete questionnaires that are available only in those two languages
• Participants with a high suspicion of cancer: High suspicion of ovarian cancer,
pancreatic cancer, kidney cancer, or melanoma by clinical and/or radiological
assessment, with plans for histologic or cytologic confirmation within 28 days after
study blood draw
* Examples of highly suspicious cases include: elevated CA125 and abnormal
transvaginal ultrasound, suspicious renal or pancreatic mass on imaging, suspicious
cutaneous lesion concerning for melanoma
• Participants with a high suspicion of cancer: Central review of radiology reports
and/or clinical documentation conducted by study chairs
• Participants with a high suspicion of cancer: Age >= 40 and =< 75
• Participants with a high suspicion of cancer: No known current pregnancy by
self-report
• Participants with a high suspicion of cancer: No known or prior history of in situ or
invasive malignancy (excluding in situ non-melanoma skin cancers) other than the
current cancer diagnosis
• Participants with a high suspicion of cancer: Willingness to provide blood samples for
research use
• Participants with a high suspicion of cancer: Absence of medical contraindications to
a research blood draw volume of 60 mL
• Participants with a high suspicion of cancer: No history or organ transplantation
• Participants with a high suspicion of cancer: Ability to read and comprehend English
or Spanish * Eligibility is restricted to individuals who can comprehend and read
English and Spanish given that participation in the study will require the ability to
read and complete questionnaires that are available only in those two languages
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, Mycosis Fungoides, 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, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Uterus, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Ann Arbor Stage I Lymphoma, Ann Arbor Stage II Lymphoma, Ann Arbor Stage III Lymphoma, Ann Arbor Stage IV Lymphoma, Chronic Lymphocytic Leukemia, Chronic Myeloid Leukemia, Gastroesophageal Junction Adenocarcinoma, Head and Neck Carcinoma, Hematopoietic and Lymphoid Cell Neoplasm, Invasive Breast Carcinoma, Kidney Carcinoma, Malignant Hepatobiliary Neoplasm, Malignant Solid Neoplasm, Melanoma, Muscle-Invasive Bladder Carcinoma, RISS Stage I Plasma Cell Myeloma, RISS Stage II Plasma Cell Myeloma, RISS Stage III Plasma Cell Myeloma, Sarcoma, Stage I Bladder Cancer AJCC v6 and v7, Stage I Breast Cancer AJCC v7, Stage I Colorectal Cancer AJCC v6 and v7, Stage I Esophageal Cancer AJCC V7, Stage I Gastric Cancer AJCC V7, Stage I Lung Cancer AJCC v7, Stage I Ovarian Cancer AJCC v6 and v7, Stage I Pancreatic Cancer AJCC v6 and v7, Stage I Prostate Cancer AJCC v7, Stage I Uterine Corpus Cancer AJCC v7, Stage II Bladder Cancer AJCC v6 and v7, Stage II Breast Cancer AJCC v6 and v7, Stage II Colorectal Cancer AJCC v7, Stage II Esophageal Cancer AJCC v7, Stage II Gastric Cancer AJCC v7, Stage II Lung Cancer AJCC v7, Stage II Ovarian Cancer AJCC v6 and v7, Stage II Pancreatic Cancer AJCC v6 and v7, Stage II Prostate Cancer AJCC v7, Stage II Uterine Corpus Cancer AJCC v7, Stage III Bladder Cancer AJCC v6 and v7, Stage III Breast Cancer AJCC v7, Stage III Colorectal Cancer AJCC v7, Stage III Esophageal Cancer AJCC v7, Stage III Gastric Cancer AJCC v7, Stage III Lung Cancer AJCC v7, Stage III Ovarian Cancer AJCC v6 and v7, Stage III Pancreatic Cancer AJCC v6 and v7, Stage III Prostate Cancer AJCC v7, Stage III Uterine Corpus Cancer AJCC v7, Stage IV Bladder Cancer AJCC v7, Stage IV Breast Cancer AJCC v6 and v7, Stage IV Colorectal Cancer AJCC v7, Stage IV Esophageal Cancer AJCC v7, Stage IV Gastric Cancer AJCC v7, Stage IV Lung Cancer AJCC v7, Stage IV Ovarian Cancer AJCC v6 and v7, Stage IV Pancreatic Cancer AJCC v6 and v7, Stage IV Prostate Cancer AJCC v7, Stage IV Uterine Corpus Cancer AJCC v7, Thyroid Gland Carcinoma
This is a pediatric basket study to investigate the safety and efficacy of afamitresgene
autoleucel in HLA-A*02 eligible and MAGE-A4 positive subjects aged 2-21 years of age with
advanced cancers
Christian Capitini, MD
All
2 Years to 21 Years old
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05642455
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Inclusion Criteria:
• Age 2-21 years
• Body weight ≥ 10 kg
• Subject has histologically confirmed diagnosis of any one of the following cancers:
(A) Synovial Sarcoma, (B) MPNST, (C) Neuroblastoma, or (D) Osteosarcoma
• Must have previously received a systemic chemotherapy
• Measurable disease according to RECIST v1.1 (or INCR, 2017 Neuroblastoma only).
• HLA-A*02 positive
• Tumor shows MAGE-A4 expression confirmed by central laboratory.
• Performance Status: ECOG 0-1 or Lansky Score ≥ 80
Exclusion Criteria:
• HLA-A*02:05 in either allele; or any A*02 having same protein sequence as HLA-A*02:05
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to fludarabine, cyclophosphamide.
• History of autoimmune or immune mediated disease
• Known central nervous system (CNS) metastases.
• Other prior malignancy that is not considered by the Investigator to be in complete
remission
• Clinically significant cardiovascular disease
• Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C
virus, or human T cell leukemia virus
• Pregnant or breastfeeding
Synovial Sarcoma, Malignant Peripheral Nerve Sheath Tumor (MPNST), Neuroblastoma, Osteosarcoma, 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, 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
Colon Adjuvant Chemotherapy Based on Evaluation of Residual Disease (CIRCULATE-US)
This Phase II/III trial will evaluate the what kind of chemotherapy to recommend to patients
based on the presence or absences of circulating tumor DNA (ctDNA) after surgery for colon
cancer.
Dustin Deming, MD
All
18 Years and over
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT05174169
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Inclusion Criteria:
The patient must have an ECOG performance status of 0 or 1.
Patients must have histologically/pathologically confirmed colon adenocarcinoma (T1-3,
N1/N1c) with R0 resection accordingly to AJCC 8th edition criteria. NOTE: Patients with
pathologic stages II or IIIC colon adenocarcinoma with R0 resection who have a commercially
obtained Signatera™ ctDNA+ve assay result post-operatively meeting all timelines and
eligibility requirements otherwise, are eligible for enrollment and inclusion in Cohort B.
No radiographic evidence of overt metastatic disease within 28 days prior to study entry
(CT with IV contrast or MRI imaging is acceptable and must include chest, abdomen, and
pelvis).
The distal extent of the tumor must be greater than or equal to 12 cm from the anal verge
on colonoscopy or above the peritoneal reflection as documented during surgery or on
pathology specimen (i.e., excluding rectal adenocarcinomas warranting treatment with
chemoradiation).
The patient must have had an en bloc complete gross resection of tumor (curative
resection). Patients who have had a two-stage surgical procedure, to first provide a
decompressive colostomy and then in a later procedure to have the definitive surgical
resection, are eligible.
The resected tumor specimen and a blood specimen from patients with Stage IIIA or Stage
IIIB colon cancer must have central testing for ctDNA using the Signatera™ assay by Natera.
NOTE: Patients with stage IIIA or IIIB colon cancer who otherwise meet eligibility criteria
and have had ctDNA status checked with the Signatera™ assay as routine care outside of the
study, are allowed to be enrolled, and will be retested and placed in either Cohort A or
Cohort B depending on the central ctDNA testing result.
NOTE: Patients with stage II or IIIC colon cancer who otherwise meet eligibility criteria
and have had ctDNA status checked with the Signatera™ assay as routine care outside of the
study AND have a ctDNA+ve result, are allowed to be enrolled. Patients will have central
ctDNA testing, confirmed to be ctDNA+ve, and placed in Cohort B.
Tumor must be documented as microsatellite stable or have intact mismatch repair proteins
through CLIA-approved laboratory testing. Patients whose tumors are MSI-H or dMMR are
excluded.
The treating investigator must deem the patient a candidate for all potential agents used
in this trial (5FU, LV, oxaliplatin and irinotecan).
The interval between surgery (post-operative Day 7) and study entry must be no more than 60
days.
Availability and provision of adequate surgical tumor tissue for molecular diagnostics and
confirmatory profiling.
Adequate hematologic function within 28 days before study entry defined as follows:
• Absolute neutrophil count (ANC) must be greater than or equal to 1500/mm3;
• Platelet count must be greater than or equal to 100,000/mm3; and
• Hemoglobin must be greater than or equal to 9 g/dL.
Adequate hepatic function within 28 days before study entry defined as follows:
• total bilirubin must be less than or equal to ULN (upper limit of normal) for the lab
and
• alkaline phosphatase must be less than 2.5 x ULN for the lab; and
• AST and ALT must be less than 2.5 x ULN for the lab.
Adequate renal function within 28 days before study entry defined as serum creatinine less
than or equal to 1.5 x ULN for the lab or measured or calculated creatinine clearance
greater than or equal to 50 mL/min using the Cockroft-Gault formula for patients with
creatinine levels greater than 1.5 x ULN for the lab.
For Women Creatinine Clearance (mL/min) = (140 •age) x weight (kg) x 0.85 72 x serum
creatinine (mg/dL) For Men Creatinine Clearance (mL/min) = (140 •age) x weight (kg) 72 x
serum creatinine (mg/dL)
HIV-infected patients on effective anti-retroviral therapy with undetectable viral load
within 6 months are eligible for this trial.
Pregnancy test (urine or serum according to institutional standard) done within 14 days
before study entry must be negative (for women of childbearing potential only).
Patients receiving a coumarin-derivative anticoagulant must agree to weekly monitoring of
INR if they are randomized to Arm 1 or Arm 3 and receive capecitabine.
Eligibility Criteria for Cohort A Arm-2 patients on Second Randomization
Patient must have developed a ctDNA +ve assay during serial monitoring.
Patient's willingness to be re-randomized affirmed.
The patient must continue to have an ECOG performance status of 0 or 1.
No radiographic evidence of overt metastatic disease.
Pregnancy test (urine or serum according to institutional standard) done within 14 days
before study entry must be negative (for women of childbearing potential only).
Adequate hematologic function within 28 days before randomization defined as follows:
• Absolute neutrophil count (ANC) must be greater than or equal to 1500/mm3;
• Platelet count must be greater than or equal to 100,000/mm3; and
• Hemoglobin must be greater than or equal to 9 g/dL.
Adequate hepatic function within 28 days before randomization defined as follows:
• total bilirubin must be less than or equal to ULN (upper limit of normal) for the lab
and
• alkaline phosphatase must be less than 2.5 x ULN for the lab; and
• AST and ALT must be less than 2.5 x ULN for the lab.
Adequate renal function within 28 days before randomization defined as serum creatinine
less than or equal to 1.5 x ULN for the lab or measured or calculated creatinine clearance
greater than or equal to 50 mL/min using the Cockroft-Gault formula for patients with
creatinine levels greater than 1.5 x ULN for the lab.
For Women Creatinine Clearance (mL/min) = (140 •age) x weight (kg) x 0.85 72 x serum
creatinine (mg/dL) For Men Creatinine Clearance (mL/min) = (140 •age) x weight (kg) 72 x
serum creatinine (mg/dL)
Exclusion Criteria:
Colon cancer histology other than adenocarcinoma (i.e., neuroendocrine carcinoma, sarcoma,
lymphoma, squamous cell carcinoma, etc.).
Pathologic, clinical, or radiologic overt evidence of metastatic disease. This includes
isolated, distant, or non-contiguous intra-abdominal metastases, even if resected.
Tumor-related bowel perforation.
History of prior invasive colon malignancy, regardless of disease-free interval.
History of bone marrow or solid organ transplantation (regardless of current
immunosuppressive therapy needs). Bone grafts, skin grafts, corneal transplants and
organ/tissue donation are not exclusionary.
Any prior systemic chemotherapy, targeted therapy, or immunotherapy; or radiation therapy
administered as treatment for colorectal cancer (e.g., primary colon adenocarcinomas for
which treatment with neoadjuvant chemotherapy and/or radiation is warranted are not
permitted).
Other invasive malignancy within 5 years before study entry. Exceptions are colonic polyps,
non-melanoma skin cancer or any carcinoma-in-situ.
Synchronous primary rectal and/ or colon cancers.
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.
Sensory or motor neuropathy greater than or equal to grade 2, according to CTCAE v5.0.
Blood transfusion within two weeks before collection of blood for central ctDNA testing.
Active seizure disorder uncontrolled by medication.
Active or chronic infection requiring systemic therapy.
Known homozygous DPD (dihydropyrimidine dehydrogenase) deficiency.
Patients known to have Gilbert's Syndrome or homozygosity for UGT1A1*28 polymorphism.
Pregnancy or lactation at the time of study entry.
Co-morbid illnesses or other concurrent disease that would make the patient inappropriate
for entry into this study (i.e., unable to tolerate 6 months of combination chemotherapy or
interfere significantly with the proper assessment of safety and toxicity of the prescribed
regimens or prevent required follow-up).
Ineligibility Criteria for Cohort A Arm-2 patients on Second Randomization
Pregnancy or lactation at the time of randomization.
No longer a candidate for systemic chemotherapy (FOLFOX, CAPOX, and mFOLFIRINOX) in the
opinion of the treating investigator.
Comparing the Addition of Radiation Either Before or After Surgery for Patients With Brain Metastases
This phase III trial compares the addition of stereotactic radiosurgery before or after
surgery in treating patients with cancer that has spread to the brain (brain metastases).
Stereotactic radiosurgery is a type of radiation therapy that delivers a high dose of
radiation only to the small areas of cancer in the brain and avoids the surrounding normal
brain tissue. Surgery and radiation may stop the tumor from growing for a few months or
longer and may reduce symptoms of brain metastases.
Andrew Baschnagel, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05438212
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Inclusion Criteria:
• Radiographic confirmation of 1-4 brain metastases, one of which requires resection, as
defined by magnetic resonance imaging (MRI) with contrast obtained within 14 days
prior to registration
• The maximum diameter of the lesion to be resected on the post-contrast MRI, as
measured on any orthogonal plane (axial, sagittal, coronal), must measure > 2.0
cm and < 5.0 cm.
• The maximum diameter of the lesions not to be resected must measure < 4.0 cm
• Known active or history of invasive non-central nervous system (CNS) primary cancer
based on documented pathologic diagnosis within the past 3 years
• All brain metastases must be located > 5 mm from the optic chiasm and outside the
brainstem
• Patient is able to medically tolerate surgery and SRS
• The lesion chosen for surgical therapy must be deemed an appropriate target for safe,
gross total resection by the treating surgeon
• History/physical examination within 14 days prior to registration
• Age >= 18
• Karnofsky performance status (KPS) >= 60 within 14 days prior to registration
• A 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 for at least 12
consecutive months
• Participants who are sexually active must agree to use medically acceptable forms of
contraception during treatment on this study to prevent pregnancy
• 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:
• Prior cranial radiotherapy, including whole brain radiotherapy, or SRS to the
resection site
• Note: The index lesion to be resected cannot have been previously treated with
SRS (i.e. repeat radiosurgery to the same location/lesion is not allowed on this
protocol). Previous SRS to other lesions is allowed
• Evidence of leptomeningeal disease (LMD)
• Note: For the purposes of exclusion, LMD is a clinical diagnosis, defined as
positive cerebrospinal fluid (CSF) cytology and/or unequivocal radiologic or
clinical evidence of leptomeningeal involvement. Patients with leptomeningeal
symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be
considered to have LMD even in the absence of positive CSF cytology. In contrast,
an asymptomatic or minimally symptomatic patient with mild or nonspecific
leptomeningeal enhancement (MRI) would not be considered to have LMD. In that
patient, CSF sampling is not required to formally exclude LMD, but can be
performed at the investigator's discretion based on level of clinical suspicion
• Any medical conditions which would make this protocol unreasonably hazardous,
including, but not limited to: contraindications to general endotracheal anesthesia;
intracranial surgery; and stereotactic radiosurgery
• Primary histology of germ cell tumor, small cell carcinoma or lymphoma
• More than one brain metastasis planned for resection
• Inability to undergo MRI with contrast
• Planned administration of cytotoxic chemotherapy or tyrosine/multi-kinase inhibitors
within the 3 days prior to, the day of, or within 3 days after the completion of SRS
• Note: chemotherapy and immunotherapy outside of this window are allowed
Metastatic Malignant Neoplasm in the Brain, Colon, Rectum, Lung, Breast, Prostate, Colon and Rectum
Comparison of Chemotherapy Before and After Surgery Versus After Surgery Alone for the Treatment of Gallbladder Cancer
This phase II/III trial compares the effect of adding chemotherapy before and after surgery
versus after surgery alone (usual treatment) in treating patients with stage II-III
gallbladder cancer. Chemotherapy drugs, such as gemcitabine and 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. Giving chemotherapy before surgery may make the
tumor smaller; therefore, may reduce the extent of surgery. Additionally, it may make it
easier for the surgeon to distinguish between normal and cancerous tissue. Giving
chemotherapy after surgery may kill any remaining tumor cells. This study will determine
whether giving chemotherapy before surgery increases the length of time before the cancer may
return and whether it will increase a patient's life span compared to the usual approach.
Sam Lubner, MD
All
18 Years and over
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT04559139
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Inclusion Criteria:
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0-1
• Patient must have histologically-confirmed T2 or T3 gallbladder cancer discovered
incidentally at the time of or following routine cholecystectomy for presumed benign
disease
• NOTE: Patients with histologically-confirmed Tis, T1a, T1b, or T4 tumors are not
eligible
• Patient must have undergone initial cholecystectomy within 12 weeks prior to
randomization
• Patient must have the ability to understand and the willingness to sign a written
informed consent document
• Leukocytes >= 3,000/mcL (obtained =< 28 days prior to randomization)
• Absolute neutrophil count >= 1,500/mcL (obtained =< 28 days prior to randomization)
• Platelets >= 100,000/mcL (obtained =< 28 days prior to randomization)
• Total bilirubin =< institutional upper limit of normal (ULN) except in patients with
Gilbert's syndrome. Patients with Gilbert's syndrome are eligible if direct bilirubin
< 1.5 x ULN of the direct bilirubin (obtained =< 28 days prior to randomization)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x
institutional ULN (obtained =< 28 days prior to randomization)
• Serum creatinine =< institutional ULN OR creatinine clearance >= 50 mL/min/1.73 m^2
(Based on Cockcroft Gault estimation) (obtained =< 28 days prior to randomization)
• 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
• 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 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
Exclusion Criteria:
• Patient must not have any evidence of metastatic disease or inoperable loco-regional
disease based on high-quality, preoperative, cross-sectional imaging (computed
tomography [CT] or magnetic resonance imaging [MRI]) of the chest, abdomen, and pelvis
(C/A/P) obtained within 6 weeks prior to randomization, defined as
• No radiographic evidence of distant disease (M1 disease)
• No radiographic evidence of tumor invasion into multiple extrahepatic organs (T4
disease)
• No radiographic evidence of distant lymph node involvement (celiac, para-aortic,
para-caval lymph nodes)
• No evidence of new-onset ascites
• Soft tissue thickening within or in direct communication with the gallbladder
fossa, peri-portal lymph node involvement, involvement of one extrahepatic organ,
and other disease within the confines of what constitutes 'localized resectable'
disease are allowable
• Women must not be pregnant or breast feeding due to the potential harm to unborn fetus
and possible risk for adverse events in nursing infants with the treatment regimens
being used. All females of child bearing potential must have a serum or urine
pregnancy test to rule out pregnancy within 14 days prior to randomization. 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: 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)
• Women of childbearing potential and sexually active males must not expect to conceive
or father children by being strongly advised to use accepted and effective method(s)
of contraception or to abstain from sexual intercourse for the duration of their
participation in the study
Stage II Gallbladder Cancer AJCC v8, Stage IIA Gallbladder Cancer AJCC v8, Stage IIB Gallbladder Cancer AJCC v8, Stage III Gallbladder Cancer AJCC v8, Stage IIIA Gallbladder Cancer AJCC v8, Stage IIIB Gallbladder Cancer AJCC v8, Other Digestive Organ, Gastrointestinal cancers, other
Trial of Pre-operative Neratinib and Endocrine Therapy With Trastuzumab in ER-Positive, HER-2 Positive Breast Cancers
Patient will be treated with neratinib, an aromatase inhibitor and trastuzumab for 24 weeks
prior to surgery, following an initial 3 weeks of neratinib alone, aromatase inhibitor alone
or the combination of neratinib and an aromatase inhibitor. A breast biopsy will be performed
prior to Day 1 of week 4 of treatment. Following surgery, patients will receive standard of
care HER2-directed and endocrine therapy at the treating physician's discretion.
Kari Wisinski, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04886531
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Inclusion Criteria:
Subject must meet all of the following applicable inclusion criteria to participate in this
study:
• Written informed consent and HIPAA authorization for release of personal health
information. NOTE: HIPAA authorization may be included in the informed consent or
obtained separately.
• Age ≥ 18 years at the time of consent.
• Postmenopausal females. NOTE: Postmenopausal status defined as: prior bilateral
oophorectomy, Age ≥ 60 years, or Age < 60 years and amenorrhea for 12 or more months
in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) or an
estradiol level in postmenopausal ranges per local reference range.
• ECOG Performance Status of 0-2 within 28 days prior to registration.
• Anatomic, clinical stage I-III, invasive breast cancer, greater than 10mm
• HER2-positive (by the most recent ASCO-CAP criteria)
• ER positive (≥ 10%). NOTE: There is no requirement for PR status; PR positive or
negative allowed.
• Resectable breast cancer in which pre-operative therapy is appropriate (T > 10mm
and/or node-positive).
• Archival tissue from the diagnostic pre-treatment biopsy is required. This sample
should be identified at screening and shipped by Week 4. If archival tissue is not
available, the subject is not eligible for the study.
• Agreeable to repeat breast biopsy at 3 weeks after initiation of treatment.
• Candidate for either letrozole or anastrozole, as determined by the treating physician
• Left ventricular ejection fraction (LVEF) ≥ 50% as assessed by echocardiogram (ECHO)
or multi-gated acquisition scan (MUGA) documented within 4 weeks prior to the study
treatment.
• Demonstrate adequate organ function as defined below; all screening labs to be
obtained within 28 days prior to registration.
• Hematological
• Platelet count ≥100,000/uL
• Absolute Neutrophil Count (ANC) ≥1500/uL
• Hemoglobin (Hgb) ≥10 g/dL
• Renal
---Calculated creatinine clearance: CrCl ≥60 mL/min using the Cockcroft-Gault
formula
• Hepatic
• Bilirubin ≤1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 2.5 × ULN
• Alanine aminotransferase (ALT) ≤ 2.5 × ULN
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral
load within 6 months of registration are eligible for this trial.
• For patients with known serologic 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, the
HCV viral load must be undetectable to be eligible for this trial.
• Ability of the subject to understand and comply with study procedures for the entire
length of the study, as determined by the enrolling physician or protocol designee.
Exclusion Criteria:
Subjects meeting any of the criteria below may not participate in the study:
• Locally advanced or inflammatory breast cancer.
• Evidence of metastatic disease. Systemic imaging is not required.
• Patients with a prior or concurrent malignancy whose natural history or treatment has
the potential to interfere with the safety or efficacy assessment of the
investigational regimen are not eligible for this trial: exceptions include basal cell
or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for
which the subject has been disease-free for at least five years.
• Active infection requiring systemic therapy.
• Requirement for use of a moderate or stonr CYP3A4 inhibitor or inducer during the
study (see protocol).
• Treatment with any investigational drug within 14 days prior to registration or within
5 half-lives of the investigational product, whichever is longer.
• Subject has had major surgery within 14 days prior to registration or has not
recovered from major side effects of the surgery (tumor biopsy is not considered as
major surgery).
• Any impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of study drugs (e.g., ulcerative diseases, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome, or small bowel resection) or significantly
impair the ability to swallow capsules/tablets.
• Known history of myelodysplastic syndrome or acute myeloid leukemia.
• Subjects with any of the following conditions:
• History of abdominal fistula, gastrointestinal perforation, or intra- abdominal
abscess within 28 days prior to registration.
• Any history of cerebrovascular accident (CVA) or transient ischemic attack within
12 months prior to registration.
• History of acute coronary syndromes (including myocardial infarction, unstable
angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or
symptomatic pericarditis within 6 months prior to registration.
• Symptomatic congestive heart failure (New York Heart Association III-IV) or
documented current cardiomyopathy with left ventricular ejection fraction (LVEF)
<50%.
• Clinically significant cardiac ventricular arrhythmias (e.g. sustained
ventricular tachycardia/ventricular fibrillation) or high-grade AV block (e.g.
bifascicular block, Mobitz type II and third-degree AV block) unless a pacemaker
is in place.
• Long QT syndrome or family history of idiopathic sudden death or congenital long
QT syndrome.
• Any concurrent severe and/or uncontrolled medical condition that would, in the
investigator's judgment, cause unacceptable safety risks, contraindicate subject
participation in the clinical study or compromise compliance with the protocol.
Breast Cancer, HER2-positive Breast Cancer, ER Positive Breast Cancer, PR-Positive Breast Cancer, Breast
Testing the Safety and Effectiveness of Radiation-based Treatment (Lutetium Lu 177 Dotatate) for Metastatic Prostate Cancer That Has Neuroendocrine Cells
This phase II trial studies how well lutetium Lu 177 dotatate works in treating patients with
prostate cancer with neuroendocrine differentiation that has spread to other places in the
body (metastatic). Neuroendocrine differentiation refers to cells that have traits of both
hormone-producing endocrine cells and nerve cells. These cells release hormones into the
blood in response to a signal from the nervous system. Hormones are biological substances
that circulate through the bloodstream to control the activity of other organs or cells in
the body. Lutetium Lu 177-dotate is a radioactive drug. It binds to a protein called
somatostatin receptor, which is found on some neuroendocrine tumor cells. Lutetium Lu
177-dotatate builds up in these cells and gives off radiation that may kill them. It is a
type of radioconjugate and a type of somatostatin analog. Treatment with Lutetium Lu 177
dotatate may shrink the tumor in a way that can be measured in patients with metastatic
prostate cancer with neuroendocrine differentiation.
John Floberg, Assistant Professor
Male
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05691465
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Inclusion Criteria:
• PRE-REGISTRATION ELIGIBILITY
• Patients must have metastatic prostate cancer with neuroendocrine differentiation, as
determined by at least one of the following:
• Histologically confirmed small cell or neuroendocrine cancer from a primary
prostate or metastatic biopsy. Neuroendocrine prostate cancer includes mixed
small cell with adenocarcinoma histology, as well as small or large cells with
positive neuroendocrine markers (e.g., chromogranin or synaptophysin)
• Prostate adenocarcinoma with molecular features of neuroendocrine differentiated
cancer (e.g., 2 of the following 3: PTEN, TP53, or RB loss)
• Progression of visceral metastases in the absence of PSA progression
• Serum chromogranin A > 5x normal limit, or neuron-specific enolase > 2x normal
• Age >= 18 years. Prostate cancer is typically a disease of older men, with the average
age at diagnosis being 65 years. Consequently, because the research topic is not
relevant to children, no children will be included in this study. There is no upper
limit to the age of participants eligible for this study
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 8 g/dL, prior to each dose of lutetium lu 177 dotatate
• 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
• Creatinine Cockcroft calculated creatinine clearance of >= 60 mL/min OR
• Glomerular filtration rate (GFR) of 60 mL/min/1.73 m^2 unless data exists supporting
safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2
• 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
• 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 should be New York Heart Association Functional Classification of class 2B or
better
• Current disease progression according to PCWG3 criteria
• Ongoing use of luteinizing hormone-releasing hormone (LHRH) agonists/antagonists will
be required (unless prior bilateral orchiectomy or pure neuroendocrine carcinoma
histology) to maintain testosterone at castrate levels. Patients with a pure
neuroendocrine carcinoma histology do not need to be undergoing LHRH
agonist/antagonist therapy
• No concurrent use of other anti-cancer therapies
• Pregnancy Precaution: The effects of lutetium lu 177 dotatate on the developing human
fetus are unknown. For this reason and because radionuclides are known to be
teratogenic, male participants and their female partners must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to study
entry and for the duration of study participation. Should a woman become pregnant or
suspect she is pregnant while her male partner is participating in this study, she
should inform her treating physician immediately. Men treated or enrolled on this
protocol must also agree to use adequate contraception prior to the study, for the
duration of study participation, and 4 months after completion of lutetium lu 177
dotatate administration. Patients must not donate sperm during the study and for 3
months after the last study drug administration
• Ability to understand and the willingness to sign a written informed consent document.
Participants with impaired decision-making capacity who have a legally-authorized
representative (LAR) and/or family member available will also be eligible
• Patients will undergo a Gallium 68 Dotatate PET scan after enrollment. The Gallium 68
Dotatate PET must be positive to proceed with lutetium Lu 177 dotatate therapy. A
positive scan will be defined as at least one lesion with an maximum standardized
uptake value (SUVmax) > the average standardized uptake value (SUV) of normal liver.
The positive lesion(s) can be in any location (bone metastases or visceral
metastases). Patients with only bone metastases will be allowed
• REGISTRATION ELIGIBILITY: The gallium 68 dotatate PET is positive. A positive scan
will be defined as at least one lesion with an maximum standardized uptake value
(SUVmax) > the average SUV of normal liver. The positive lesion(s) can be in any
location (bone metastases or visceral metastases). Patients with only bone metastases
will be allowed.
• REGISTRATION ELIGIBILITY: Absolute neutrophil count ≥ 1,500/mcL
• REGISTRATION ELIGIBILITY: Platelets ≥ 100,000/mcL
• REGISTRATION ELIGIBILITY: Hemoglobin ≥ 8 g/dL, prior to each dose of lutetium Lu 177
dotatate
• REGISTRATION ELIGIBILITY: Total bilirubin ≤1.5 × institutional upper limit of normal
(ULN)
• REGISTRATION ELIGIBILITY: AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN
• REGISTRATION ELIGIBILITY: Creatinine Cockcroft calculated creatinine clearance of ≥ 60
mL/min OR
• REGISTRATION ELIGIBILITY: Glomerular filtration rate (GFR) of 60 mL/min/1.73 m^2
unless data exists supporting safe use at lower kidney function values, no lower than
30 mL/min/1.73 m^2
Exclusion Criteria:
• Patients who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to Lutetium Lu 177 dotatate
• As per the Food and Drug Administration (FDA) package insert for Lutetium Lu 177
dotatate, use of long-acting somatostatin analogs (e.g., long-acting octreotide) is
prohibited within 4 weeks prior to initiating Lutetium Lu 177 dotatate and during
treatment. Use of short-acting somatostatin analogs is prohibited within 24 hours
prior to initiating Lutetium Lu 177 dotatate and during treatment. Long-acting
somatostatin analogs or short-acting somatostatin analogs will be allowed if the
patient has a history of carcinoid syndrome and requires long-acting or short-acting
somatostatin analogs for the control of his functional syndrome
• Patients with uncontrolled intercurrent illness
• Any of the following within 6 months before starting treatment: stroke, myocardial
infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft;
congestive heart failure New York Heart Association (NYHA) Class III or IV
• Uncontrolled hypertension as indicated by a systolic blood pressure >= 160 mmHg or
diastolic blood pressure >= 100 mmHg at screening
Metastatic Prostate Adenocarcinoma With Neuroendocrine Differentiation, Metastatic Prostate Neuroendocrine Carcinoma, Metastatic Prostate Small Cell Neuroendocrine Carcinoma, Stage IV Prostate Cancer AJCC v8, Prostate
Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial
This ComboMATCH patient screening trial is the gateway to a coordinated set of clinical
trials to study cancer treatment directed by genetic testing. Patients with solid tumors that
have spread to nearby tissue or lymph nodes (locally advanced) or have spread to other places
in the body (advanced) and have progressed on at least one line of standard systemic therapy
or have no standard treatment that has been shown to prolong overall survival may be
candidates for these trials. Genetic tests look at the unique genetic material (genes) of
patients' tumor cells. Patients with some genetic changes or abnormalities (mutations) may
benefit from treatment that targets that particular genetic mutation. ComboMATCH is designed
to match patients to a treatment that may work to control their tumor and may help doctors
plan better treatment for patients with locally advanced or advanced solid tumors.
Nataliya Uboha, MD
All
Not specified
Phase 2
This study is NOT accepting healthy volunteers
NCT05564377
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patient must have measurable disease
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status
between 0-2 OR patient must have Lansky performance status of >= 50% or Karnofsky
performance status of >= 50%
• Patient must be deemed potentially eligible for a ComboMATCH Treatment Trial as
assessed by the enrolling provider
• All patients must have sequencing results available from a National Cancer Institute
(NCI) credentialed Designated Laboratory (DL)
• Patients must have locally advanced or advanced histologically documented solid tumors
requiring therapy and meet one of the following criteria:
• Patients must have progressed on at least one line of standard systemic therapy
OR
• Patients whose disease has no standard treatment that has been shown to prolong
overall survival
• Patient must meet one of the following requirements:
• Patients 18 years and older who have tumor amenable to minimal risk image-guided
or direct vision biopsy and must be willing and able to undergo a tumor biopsy to
obtain samples for research if the patient is to enroll in a ComboMATCH treatment
trial OR
• Patients 18 years and older who do not have disease that is biopsiable at minimal
risk to the patient must confirm availability of an archival tumor tissue
specimen for submission for research if the patient enrolls to a ComboMATCH
Treatment Trial. This tumor tissue must meet the following criteria:
• Tissue must have been collected within 12 months prior to registration to
the EAY191 Registration Trial
• Patient must not have had a Response Evaluation Criteria in Solid Tumors
(RECIST) response (complete response [CR] or partial response [PR]) to any
intervening therapy after collection of the tissue
• Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be
available OR
• Patients under 18 years old must confirm availability of an archival tumor tissue
specimen for submission for research if patient enrolls to a ComboMATCH Treatment
Trial. This tumor tissue must meet the following criteria:
• Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be
available
• NOTE: See specific ComboMATCH Treatment Trial protocol for tissue collection and
management instructions. Performance of the mandatory research biopsy or
submission of pre-trial formalin-fixed paraffin-embedded (FFPE) and collection
and submission of the blood specimens for the integrated studies will be
performed under the consent authority of the specific treatment trial protocol to
which the patient is registered. No procedures to collect specimens for research
only are to be performed for patients registered to the EAY191 Registration Trial
only
• NOTE: Each ComboMATCH Treatment Trial contains specific eligibility criteria. If
patient is found to not be eligible for the assigned ComboMATCH Treatment Trial,
indication of ineligibility will trigger re-evaluation and potential assignment to
another Treatment Trial
Advanced Malignant Solid Neoplasm, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Locally Advanced Malignant Solid Neoplasm, Malignant Female Reproductive System Neoplasm, Metastatic HER2-Negative Breast Carcinoma, Metastatic Malignant Solid Neoplasm, Recurrent Endometrial Carcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Malignant Female Reproductive System Neoplasm, Recurrent Malignant Solid Neoplasm, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma, Unresectable HER2-Negative Breast Carcinoma, Unresectable Malignant Solid Neoplasm, 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, Unknown Sites, 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
Study of Chemotherapy Plus Ipatasertib for People With Solid Tumors With AKT Mutations, A ComboMATCH Treatment Trial
This phase II ComboMATCH treatment trial tests the usual treatment of chemotherapy
(paclitaxel) plus ipatasertib in patients with solid tumor cancers that that cannot be
removed by surgery (unresectable), has spread to nearby tissue or lymph nodes (locally
advanced) or from where it first started (primary site) to other places in the body
(metastatic), and has an AKT genetic change. Chemotherapy drugs, such as paclitaxel, 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. Targeted therapy, such as
Ipatasertib, may stop the growth of tumor cells by blocking some of the enzymes needed for
cell growth. The addition of ipatasertib to paclitaxel in solid tumors with an AKT genetic
change could increase the percentage of tumors that shrink as well as lengthen the time that
the tumors remain stable (without progression). Researchers hope to learn if paclitaxel plus
ipatasertib will shrink this type of cancer or stop its growth.
Nataliya Uboha, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05554380
Show full eligibility criteria
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Inclusion Criteria:
• Patient must have enrolled onto EAY191 and must have been given a treatment assignment
to ComboMATCH to EAY191-S3 based on the presence of an actionable mutation as defined
in EAY191
• GENERAL COMBOMATCH EAY191 REGISTRATION INCLUSION CRITERIA:
• Participants must be enrolled on the ComboMATCH Master Registration Trial EAY191
• Participants must have an activating AKT mutation (a known mutation in AKT1, AKT2, or
AKT3, a single nucleotide variant, insertion, or deletion) as determined by the
ComboMATCH screening assessment
• GENERAL COMBOMATCH EAY191 REGISTRATION EXCLUSION CRITERIA:
• Participants must not have an activating KRAS, NRAS, HRAS, or BRAF mutation (a single
nucleotide variant, insertion, or deletion) as determined by the ComboMATCH screening
assessment
• Participants must have disease that can be safely biopsied and agree to a
pre-treatment biopsy or have archival tissue available from within 12 months prior to
the date of registration on the ComboMATCH Registration Trial (EAY191)
• Participants must have a histologically confirmed non-breast solid malignancy
• Participants must have locally advanced, unresectable, or metastatic disease in the
opinion of the treating investigator
• Participants must have measurable disease documented by CT or MRI. Measurable disease
must be assessed within 28 days prior to registration. Non-measurable disease must be
assessed within 42 days prior to registration. The CT from a combined positron
emission tomography (PET)/CT may be used only if it is of diagnostic quality. All
known sites of disease must be assessed and documented on the Baseline Tumor
Assessment Form (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).
Participants whose only measurable disease is within a previous radiation therapy port
must demonstrate clearly progressive disease (in the opinion of the treating
investigator) prior to registration
• Participants with known brain metastases must have a CT/MRI scan to evaluate for
central nervous system (CNS) disease and show no evidence of progression within 42
days prior to registration
• Participants must have completed any CNS-directed therapy and/or local therapy for
spinal cord compression at least 28 days prior to registration
• Participants must not have spinal cord compression or brain metastases unless: (1)
metastases have been locally treated and have remained clinically controlled and
asymptomatic for at least 14 days prior to registration, AND (2) participant has no
residual neurological dysfunction and has been off corticosteroids for at least 24
hours prior to registration
• Participants must not have leptomeningeal disease
• Participants must have progressed within 6 months of taxane-based therapy in the
neoadjuvant/adjuvant or metastatic setting
• Participants must not have received any prior AKT inhibitor (e.g., capivasertib or
ipatasertib); prior PI3K/mTOR inhibitor is acceptable
• Participants must not be planning to receive any concurrent chemotherapy,
immunotherapy, biologic, radiation, or hormonal therapy for cancer treatment while
receiving treatment on this study
• Participants must be >= 18 years of age
• Participants must be able to swallow oral medications whole
• Participants must have a pre-study history and physical exam done within 28 days prior
to registration
• Participants must have a Zubrod performance status of 0-2 within 28 days prior to
registration
• Participants must have adverse events resolved =< grade 1 related to any prior
therapy, except alopecia within 14 days prior to registration
• Participants with neuropathy must have resolved to < grade 2 within 14 days prior to
registration
• Leukocytes >= 3 x 10^3/uL (within 28 days prior to registration)
• Absolute neutrophil count >= 1.5 x 10^3/uL (within 28 days prior to registration)
• Platelets >= 100 x 10^3/uL (within 28 days prior to registration)
• Total bilirubin =< institutional upper limit of normal (ULN) unless history of
Gilbert's disease. Participants with history of Gilbert's disease must have total
bilirubin =< 5 x institutional ULN (within 28 days prior to registration)
• Aspartate aminotransferase (AST) & alanine aminotransferase (ALT) =< 3 x institutional
ULN (within 28 days prior to registration)
• Participants must have adequate cardiac function, class IIB (2B) or better.
Participants with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification
• Participants must have a measured OR calculated creatinine clearance >= 50 mL/min
using the following Cockcroft-Gault formula. This specimen must have been drawn within
28 days prior to registration
• Participants with known human immunodeficiency virus (HIV)-infection must be receiving
anti-retroviral therapy and have an undetectable viral load test on the most recent
test results obtained within 6 months prior to registration
• Participants with evidence of chronic hepatitis B virus (HBV) infection must have
undetectable HBV viral load on suppressive therapy within 28 days prior to
registration
• Participants with a history of hepatitis C virus (HCV) infection must have been
treated and cured. Participants with HCV infection who are currently on treatment must
have an undetectable HCV viral load within 28 days prior to registration
• Participants must have an electrocardiography (ECG) performed (if clinically indicated
with a corrected QTc interval of =< 470 msec) within 28 days prior to registration
• Participants must not have a history of allergic reactions attributed to compounds of
similar chemical or biologic composition to ipatasertib and/or paclitaxel
• Participants must not have an active small/large bowel inflammation such as ulcerative
colitis or Crohn's disease
• Participants must not have grade 2 or higher uncontrolled intercurrent illness
• NOTE: To receive an agent, participant must not have any uncontrolled
intercurrent illness requiring antibiotic/antiviral/antifungal therapy or
interventional procedures. Participants with infections unlikely to be resolved
within 2 weeks following registration should not be considered for the trial
• Participants must not have a known grade 2 or higher uncontrolled or untreated
hypercholesterolemia or hypertriglyceridemia
• Participants must not have any of the following:
• Cirrhosis at a level of Child-Pugh B (or worse),
• Cirrhosis (any degree) and a history of hepatic encephalopathy, or
• Clinically meaningful ascites resulting from cirrhosis. Clinically meaningful
ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis
• Participants must not be receiving any medications or substances that are inhibitors
or inducers of CYP3A. Treatment with strong CYP3A inhibitors or strong CYP3A inducers
within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to
initiation of study drug is prohibited.
• NOTE: 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 participant 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 participant is considering a new over-the-counter
medicine or herbal product. The participant wallet card should be presented to
the participant
• Participants must not have baseline fasting glucose (after 8-hour fast) > 160 mg/dL
(8.9 mmol/L) within 28 days prior to registration
• Participants with known diabetes mellitus must not require insulin therapy or have a
baseline fasting glucose >150 mg/dL (8.3 mmol/L) or high glycosylated hemoglobin
(Hb)A1c, (>= 8.0%), suggesting poorly controlled diabetes
• Participants who are on a stable dose of oral diabetes medication >= 2 weeks prior to
initiation of study drug treatment are eligible for enrollment
• Participants with a prior or concurrent malignancy whose natural history or treatment
(in the opinion of the treating physician) must not have a potential to interfere with
the safety or efficacy assessment of the investigational regimen
• Participants must not have lung disease requiring active systemic therapy or placing
participants at increased risk of toxicity related to study-directed therapy
including, but not limited to pneumonitis, interstitial lung disease, idiopathic
pulmonary fibrosis, cystic fibrosis, aspergillosis, active tuberculosis, or history of
opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia)
• Participants must not be pregnant or nursing. Individuals who are of reproductive
potential must have agreed to use an effective contraceptive method with details
provided as a part of the consent process. A person who has had menses at any time in
the preceding 12 consecutive months or who has semen likely to contain sperm is of
"reproductive potential". In addition to routine contraceptive methods, "effective
contraception" also includes surgery intended to prevent pregnancy (or with a
side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy,
bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the
semen
• Participants must not have psychiatric illness/social situations that would limit
compliance with study requirements
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, 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, Unknown Sites, Ill-Defined Sites, Any Site, 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, Locally Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, Unresectable Malignant Solid Neoplasm
Study Transplanting Bone Marrow Cells Into Salivary Glands to Treat Dry Mouth Caused by Radiation Therapy
The goal of this clinical research study is to evaluate the safety and tolerability of
injecting certain cells that you produce in your bone marrow called mesenchymal stem cells
(MSCs) into your salivary glands.
Participants will have head and neck cancer that was treated with radiation therapy, and in
this study will:
- Undergo a collection of bone marrow using a needle;
- Donate saliva;
- Undergo a salivary gland ultrasound; and,
- Complete questionnaires that ask about dry mouth
Participants can expect to be in this study for up to 30 months.
Randall Kimple, MD, PhD
All
18 Years to 90 Years old
Phase 1
This study is NOT accepting healthy volunteers
NCT05820711
Show full eligibility criteria
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Inclusion Criteria:
• History of histological diagnosis of head and neck cancer (HNC) that was treated with
radiation therapy and currently clinically or radiologically no evidence of disease
(NED)
• Xerostomia, defined as patient reported salivary function (pre-treatment) ≤ 80% of
healthy (pre-radiation)
• ≥ 18 years of age, ≤ 90 years of age.
• Patients ≥ 2 years from completion of radiation therapy for HNC
• Karnofsky performance status ≥ 70, patient eligible for bone marrow aspirate with
wakeful anesthesia
• Willing and able to give informed consent
• Radiographically confirmed submandibular gland(s)
Exclusion Criteria:
• Salivary gland disease (i.e., sialolithiasis)
Head and Neck Cancer, Xerostomia, Lip, Oral Cavity and Pharynx, Larynx, Head and Neck
ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study) (ACTION)
This is a randomized, double-blind, placebo-controlled, parallel-group, international, Phase
3 study in patients with newly diagnosed H3 K27M-mutant diffuse glioma to assess whether
treatment with ONC201 following frontline radiotherapy will extend overall survival and
progression-free survival in this population. Eligible participants will have histologically
diagnosed H3 K27M-mutant diffuse glioma and have completed standard frontline radiotherapy.
Ankush Bhatia, M.D.
All
Not specified
Phase 3
This study is NOT accepting healthy volunteers
NCT05580562
Show full eligibility criteria
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Inclusion Criteria:
1. Able to understand the study procedures and agree to participate in the study by
providing written informed consent (by participant or legally authorized
representative), and assent when applicable.
2. Body weight ≥ 10 kg at time of randomization.
3. Histologically diagnosed H3 K27M-mutant diffuse glioma (new diagnosis). Detection of a
missense K27M mutation in any histone H3-encoding gene detected by testing of tumor
tissue (immunohistochemistry [IHC] or next-generation sequencing [NGS] in a Clinical
Laboratory Improvement Amendments [CLIA]-certified or equivalent laboratory). [Site to
provide (as available): ≥ 10 unstained formalin-fixed paraffin-embedded (FFPE) slides
from tumor tissue.]
4. At least one, high-quality, contrast-enhanced MRI of the brain obtained prior to
starting radiotherapy for submission to sponsor's imaging vendor for central read. For
participants who had a surgical resection, this scan must be post-resection; for
participants who did not have a resection, this scan may be pre- or post-biopsy.
5. At least one, high-quality, contrast-enhanced MRI of the brain obtained 2 to 6 weeks
after completion of frontline radiotherapy. If unable to obtain contrast-enhanced
imaging due to lack of venous access after multiple attempts, a patient may still be
eligible after collection of a nonenhanced MRI of the brain. [Site to also provide all
available MRIs completed prior to initiating treatment with study intervention.]
6. Received frontline radiotherapy
1. Initiated radiotherapy within 12 weeks from the initial diagnosis of H3
K27M-mutant diffuse glioma.
2. Completed radiotherapy within 2 to 6 weeks prior to randomization
3. Completed standard fractionated radiotherapy (eg. 54 to 60 Gy in 28 to 33
fractions given over approximately 6 weeks or hypofractionated radiotherapy (eg.
40 Gy in 15 fractions given over approximately 3 weeks).
7. Karnofsky Performance Status or Lansky Performance Status ≥ 70 at time of
randomization.
8. Stable or decreasing dose of corticosteroids and anti-seizure medications for 7 days
prior to randomization, if applicable. Stable steroid dose is defined as ≤ 2 mg/day
increase (based on dexamethasone dose or equivalent dose of an alternative steroid).
Exclusion Criteria:
1. Primary spinal tumor.
2. Diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter
and diffuse involvement of the pons.
3. Evidence of leptomeningeal spread of disease or cerebrospinal fluid dissemination.
4. Any known concurrent malignancy.
5. New lesion(s) outside of the radiation field.
6. Received whole-brain radiotherapy.
7. Received proton therapy for glioma.
8. Use of any of the following treatments within the specified time periods prior to
randomization:
1. ONC201 or ONC206 at any time.
2. Systemic bevacizumab (includes biosimilars) at any time since the initial
diagnosis of H3 K27M-mutant diffuse glioma.
3. Temozolomide within past 3 weeks.
4. Tumor treating fields at any time.
5. DRD2 antagonist within past 2 weeks.
6. Any investigational therapy within past 4 weeks.
7. Strong CYP3A4 inhibitors within 3 days.
8. Strong CYP3A4 inducers (includes enzyme-inducing antiepileptic drugs) within 2
weeks.
9. Laboratory test results meeting any of the following parameters within 2 weeks prior
to randomization:
1. Absolute neutrophil count < 1.0 × 109/L or platelets < 75 × 109/L.
2. Total bilirubin > 1.5 × upper limit of normal (ULN) (participants with Gilbert's
syndrome may be included with total bilirubin > 1.5 × ULN if direct bilirubin is
≤ 1.5 × ULN).
3. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × ULN.
4. Creatinine clearance ≤ 60 mL/min as calculated by the Cockcroft Gault equation
(or estimated glomerular filtration rate < 60 mL/min/1.73 m2).
10. QTc > 480 msec (based on mean from triplicate electrocardiograms) during screening.
11. Known hypersensitivity to any excipients used in the study intervention formulation.
12. Pregnant, breastfeeding, or planning to become pregnant while receiving study
intervention or within 3 months after the last dose. Participants of childbearing
potential must have a negative serum pregnancy test within 72 hours prior to receiving
the first dose of study intervention.
13. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection requiring systemic therapy or psychiatric illness/social situations that
would limit compliance with study requirements.
14. Any other condition (eg, medical, psychiatric, or social) that, in the opinion of the
investigator, may interfere with participant safety or the ability to complete the
study according to the protocol.
Brain and Nervous System, Brain/Central Nervous System, H3 K27M, Glioma
Brightline-2: A Study to Test Whether Brigimadlin (BI 907828) Helps People With Cancer in the Biliary Tract, Pancreas, Lung or Bladder
This study is open to adults with advanced cancer in the biliary tract, pancreas, lung, or
bladder. This is a study for people for whom previous treatment was not successful or no
treatment exists.
The purpose of this study is to find out whether a medicine called BI 907828 helps people
with cancer in the biliary tract, pancreas, lung, or bladder. BI 907828 is a so-called MDM2
inhibitor that is being developed to treat cancer. All participants take BI 907828 as a
tablet once every 3 weeks. Participants may continue to take BI 907828 as long as they
benefit from treatment and can tolerate it. They visit the study site regularly. At the study
site, doctors regularly check the size of the tumour and whether it has spread to other parts
of the body. The doctors also regularly check participants' health and take note of any
unwanted effects.
Jeremy Kratz, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05512377
Show full eligibility criteria
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Inclusion Criteria:
• Diagnosis of a solid tumour which meets the criteria for an open trial cohort:
• Cohorts 1 and 1-CN (biliary tract adenocarcinoma): Locally advanced or metastatic
biliary tract adenocarcinoma (intra- and extrahepatic cholangiocarcinoma,
gallbladder cancer, and ampullary cancer).Patients must have unresectable disease
and have received all available conventional therapies known to confer clinical
benefit for their disease based on local approved standards; or (in the opinion
of the investigator) patients are unlikely to tolerate or derive clinically
meaningful benefit from appropriate standard of care therapy.
• Cohort 2 (pancreatic ductal adenocarcinoma): Locally advanced or metastatic
pancreatic ductal adenocarcinoma. Patients must have unresectable disease and
have received all available conventional therapies known to confer clinical
benefit for their disease based on local approved standards.
• Cohort 3 (lung adenocarcinoma): Locally advanced or metastatic lung
adenocarcinoma. Patients must have unresectable disease and have received all
available conventional therapies known to confer clinical benefit for their
disease based on local approved standards.
• Cohort 4 (urothelial bladder cancer): Locally advanced or metastatic urothelial
bladder cancer. Patients must have unresectable disease and have received all
available conventional therapies known to confer clinical benefit for their
disease based on local approved standards.
• Written pathology report / molecular profiling report indicating Mouse double minute 2
homolog (MDM2) amplification or a copy number ≥8 and tumor protein 53 (TP53) wild-type
status. This must have been confirmed with a tissue-based test. A test with liquid
biopsy is not accepted.
• Archival tissue (formalin fixed paraffin embedded [FFPE] tumour blocks or slides) must
be provided for retrospective confirmation of MDM2 amplification and TP53 status.
• Presence of at least 1 measurable target lesion according to Response Evaluation
Criteria in Solid Tumours (RECIST) version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Patient must be willing to donate mandatory blood samples for the pharmacokinetics,
pharmacodynamics, and biomarker analyses
• Adequate organ function
• All toxicities related to previous anti-cancer therapies have resolved to ≤Common
Terminology Criteria for Adverse Events (CTCAE) Grade 1 prior to trial treatment
administration (except for alopecia and amenorrhea / menstrual disorders which can be
of any grade and peripheral neuropathy which must be ≤CTCAE Grade 2).
• Life expectancy ≥3 months at the start of treatment in the opinion of the
investigator.
• Provision of signed and dated, written informed consent form (ICF) in accordance with
ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or
analyses.
• Male or female patients ≥18 years old at the time of signature of the ICF. Women of
childbearing potential (WOCBP) and men able to father a child must be ready and able
to use 2 medically acceptable methods of birth control per ICH M3 (R2) that result in
a low failure rate of less than 1% per year when used consistently and correctly
beginning at screening, during trial participation, and until 6 months and 12 days
after last dose for women and 102 days after last dose for men. A list of
contraception methods meeting these criteria is provided in the patient information.
Exclusion Criteria:
• Previous administration of brigimadlin (BI 907828) or any other MDM2-p53 or mouse
double minute 4 (MDMX, MDM4)-p53 antagonist.
• Active bleeding, significant risk of haemorrhage (e.g. previous severe
gastrointestinal bleeding, previous haemorrhagic stroke at any time), or current
bleeding disorder (e.g. haemophilia, von Willebrand disease).
• Major surgery (major according to the investigator's assessment) performed within 4
weeks prior to start of trial treatment or planned within 6 months after screening
(e.g. hip replacement).
• Clinically significant previous or concomitant malignancies in the opinion of the
investigator affecting the efficacy and/or outcome of the trial.
• Patients who must or intend to continue the intake of restricted medications or any
drug considered likely to interfere with the safe conduct of the trial.
• Currently enrolled in another investigational device or drug trial.
• Any history of, or concomitant condition that, in the opinion of the investigator,
would compromise the patient's ability to comply with the trial or interfere with the
evaluation of the safety and efficacy of the trial drug.
• Patients not expected to comply with the protocol requirements or not expected to
complete the trial as scheduled (e.g. chronic alcohol or drug abuse or any other
condition that, in the investigator's opinion, makes the patient an unreliable trial
participant).
Further exclusion criteria apply.
Liposomal Irinotecan With TAS102 and Bevacizumab for Patients With Metastatic Colorectal Cancer
This study is being done to see if combining liposomal irinotecan with TAS102 and bevacizumab
confers clinical benefit for patients with treatment refractory metastatic colorectal cancer.
Dustin Deming, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05854498
Show full eligibility criteria
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Inclusion Criteria:
• Patients must be ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance must be 0 or 1.
• Patients must have a histologically or cytologically confirmed diagnosis of colorectal
adenocarcinoma and be metastatic or unresectable.
• The cancer must be mismatch repair proficient.
• Patients must have had prior treatment with 5-fluorouracil, oxaliplatin, irinotecan
containing regimens. If RAS wild-type must have received prior anti-EGFR therapy with
either cetuximab or panitumumab. If RAS wild-type and HER2 positive then must have had
a prior HER2 targeted therapy.
Exclusion Criteria:
• Uncontrolled concurrent medical illness that would not allow for the completion of the
planned therapy.
• Patients whose cancers possess BRAF V600 mutations are excluded.
• Patients must stop the use of strong inducers/inhibitors of CYP3A4 at least 2 weeks
before initiating therapy.
• Patients must not have mismatch repair deficient or microsatellite instability high
cancers.
• Patients must not have received prior TAS102.
Metastatic Colorectal Cancer, Colon, Colon and Rectum
(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors
This is a Phase 3, open-label, international, multicenter study of CGT9486 in combination
with sunitinib. This is a multi-part study that will enroll approximately 426 patients. Part
1 consists of two evaluations: 1) confirming the dose of an updated formulation of CGT9486 to
be used in subsequent parts in approximately 20 patients who have received at least one prior
line of therapy for GIST and 2) evaluating for drug-drug interactions between CGT9486 and
sunitinib in approximately 18 patients who have received at least two prior tyrosine kinase
inhibitors (TKIs) for GISTs. The second part of the study will enroll approximately 388
patients who are intolerant to, or who failed prior treatment with imatinib only and will
compare the efficacy of CGT9486 plus sunitinib to sunitinib alone with patients being
randomized in a 1:1 manner.
Howard Bailey, M.D.
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05208047
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Key
Inclusion Criteria:
1. Histologically confirmed locally advanced, metastatic, and/or unresectable GIST.
Molecular pathology report must be available for Part 2; if molecular pathology report
is unavailable or inadequate, an archival or fresh tumor tissue sample will be
required to evaluate mutational status prior to randomization.
2. Documented disease progression on or intolerance to imatinib
3. Subjects must have received the following treatment:
• Part 1a: Treatment with ≥1 prior lines of therapy for GIST
• Part 1b: Treatment with ≥2 prior TKI for GISTs
• Part 2: Prior treatment with imatinib only
4. Have at least 1 measurable lesion according to mRECIST v1.1
5. ECOG •0 to 2
6. Have clinically acceptable local laboratory screening results (clinical chemistry and
hematology) within certain limits
Key
Exclusion Criteria:
1. Known PDGFR driving mutations or known succinate dehydrogenase deficiency
2. Clinically significant cardiac disease
3. Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study
drug
4. Gastrointestinal abnormalities including, but not limited to, significant nausea and
vomiting, malabsorption, external biliary shunt, or significant bowel resection that
would preclude adequate absorption
5. Any active bleeding excluding hemorrhoidal or gum bleeding
6. Seropositive for HIV 1 or 2, or positive for hepatitis B surface antigen or hepatitis
C virus (HCV) antibody.
7. Active, uncontrolled, systemic bacterial, fungal, or viral infections at Screening
8. Received strong CYP3A4 inhibitors or inducers
9. Received sunitinib within 3 weeks (Part 1a, Part 1b)
Testing the Use of Steroids and Tyrosine Kinase Inhibitors With Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults
This phase III trial compares the effect of usual treatment of chemotherapy and steroids and
a tyrosine kinase inhibitor (TKI) to the same treatment plus blinatumomab. Blinatumomab is a
Bi-specific T-Cell Engager ('BiTE') that may interfere with the ability of cancer cells to
grow and spread. The information gained from this study may help researchers determine if
combination therapy with steroids, TKIs, and blinatumomab work better than the standard of
care.
Ryan Mattison, MD
All
18 Years to 75 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04530565
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Inclusion Criteria:
• ELIGIBILITY CRITERIA FOR PREREGISTRATION (TO STEP 0)
• Patient must be >= 18 and =< 75 years of age
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status
between 0-3
• Patient must be newly diagnosed with B-ALL or is suspected to have ALL
• Patient must have BCR-ABL1 positive disease. The diagnosis of ALL and the
presence of BCR-ABL translocation must be confirmed centrally. Patients can be
registered and begin Step 1 therapy while awaiting central laboratory eligibility
confirmation
• NOTE: Bone marrow aspirate and/or peripheral blood specimen must be
submitted to the American College of Radiology Imaging Network (ECOG-ACRIN)
Leukemia Laboratory at MD Anderson Cancer Center to determine patient's
eligibility for registration to Step 1 or confirm patient evaluability.
Centrally fluorescence-activated cell sorting (FACS) analysis will be
performed to determine B-ALL and to exclude acute myeloid leukemia (AML) or
acute bi-phenotypic leukemia and baseline BCR-ABL status will be determined
by fluorescent in situ hybridization (FISH). The ECOG-ACRIN Leukemia
Laboratory will forward results within 48 hours of receipt of the specimen
to the submitting institution. Bone marrow aspirate is to be from first pull
(initial or re-direct). Specimens must contain sufficient blast cells. In
cases where the bone marrow aspiration may be inadequate, or the bone marrow
examination has already been performed prior to study consent and enrollment
on Step 0, peripheral blood may be submitted, given that adequate
circulating blasts are present (> 10%). If a diagnosis of BCR-ABL positive
B-ALL has already been established by local Clinical Laboratory Improvement
Act (CLIA) certified laboratories, the patient may be registered to Step 1
without waiting for central confirmation
• Patient must not have a diagnosis of BCR/ABL T-ALL
• Patient must not have received chemotherapy for B-ALL. Patients who received up to
five days of hydroxyurea or steroids of any kind with the aim to reduce disease burden
prior to study registration to Step 1 are eligible
• Patients who started any kind of TKI prior to study registration to Step 1 are allowed
to proceed on the study if they received no more than 14 days of TKI
• Patient must not have unstable epilepsy that requires treatment
• Patients with lymphoid blast crisis CML are not eligible
• ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 1
• Patient must have a diagnosis of Philadelphia chromosome positive (Ph+) ALL that has
been determined locally and bone marrow and/or peripheral blood was sent and receipt
confirmed for central confirmation or determined centrally by the ECOG-ACRIN Leukemia
Laboratory at MD Anderson Cancer Center
• Patient must not be pregnant or breast-feeding due to 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 registration to rule out pregnancy. A patient of
childbearing potential is defined as any woman, 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 from the
time of step 1 registration, while on study treatment, and until at least six months
after the last dose of study treatment
• Total bilirubin =< 3 mg/dL (patients with Gilbert's syndrome must have a total
bilirubin =< 5 mg/dL) (obtained =< 28 days prior to step 1 registration)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 X the institutional upper limit of normal (ULN) (obtained =< 28 days prior to
step 1 registration)
• Estimated creatinine clearance > 45 mL/min (based on Cockcroft-Gault equation)
(obtained =< 28 days prior to step 1 registration)
• Patients with acute organ dysfunction at step 1 registration, which may be attributed
to leukemia can be registered regardless of lab results at presentation. Such patients
will be allowed to register and can start Arm A steroid + TKI therapy but will only be
allowed to proceed to Step 2 randomization if the eligibility criteria outlined is met
• Patients who presented with no evidence of acute organ dysfunction but during Step 0
experienced a rise in liver enzymes which investigator suspects to be a side effect of
any of prescribed drugs, are allowed to be registered regardless of the level of liver
enzymes. Step 2 Randomization must be withheld until the eligibility criteria outline
is met but no more than 14 days after concluding Arm A therapy
• 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 or on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have an undetectable
HCV viral load and if indicated, on treatment
• Patients with a prior 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 not have active concomitant malignancy. Patients on chronic hormonal
therapy for breast or prostate cancer or patients treated with maintenance with
targeted agents but are in remission with no evidence for the primary malignancies are
eligible
• 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 must be class 2B or better. An ECHO/MUGA is
required.
• Investigators must confirm which TKI patient is to receive
• NOTE: Patients with known T315I mutation status should receive ponatinib
treatment
• NOTE: In situations due to insurance coverage issues and the pre-selected TKI is
not immediately available, patients can receive dasatinib or imatinib during Step
1. The investigator must re-specify dasatinib or ponatinib prior to Step 2
randomization and from then on patients must receive the pre-selected TKI only
• ELIGIBILITY CRITERIA FOR RANDOMIZATION TO STEP 2
• Patient must have completed at least 7 and no more than 21 days of protocol-treatment
on Arm A prior to step 2 randomization. (Days in which arm A therapy was withheld for
any reason are not counted)
• NOTE: First day of steroids prescription after registration will be considered as
the first day of study therapy. The selected TKI must be initiated prior to
randomization
• Patients who presented with acute organ dysfunction within 2 weeks of registration to
step 1 must have total bilirubin =< 2 X institutional upper limit of normal (ULN)
• AST(SGOT)/ ALT(SGPT) =< 2 X the institutional upper limit of normal (ULN)
• Estimated creatinine clearance > 45 mLg/min (based on Cockcroft-Gault equation)
• Investigators must confirm which TKI patient is to receive.
• NOTE: Patients with known T315I mutation status should receive ponatinib
treatment
• For patients under age 70, intended chemotherapy regimen must have been determined
prior to randomization
• Patient must not have active central nervous system (CNS) involvement by leukemic
blasts. Patients with signs of CNS involvement at presentation are eligible for
randomization if clearance of blasts from the cerebrospinal fluid (CSF) is
demonstrated
• Patients must have resolved any serious infectious complications related to therapy
• Any significant medical complications related to therapy must have resolved
• ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 3 (RE-INDUCTION)
• Institution has received centralized MRD results confirming positive status
• Patients who presented with acute organ dysfunction within 2 weeks of registration to
step 1 must have total bilirubin =< 2 X institutional ULN
• Patients who presented with acute organ dysfunction must have AST (SGOT)/ALT (SGPT) =<
2 X institutional upper limit of normal (ULN)
• Patients who presented with acute organ dysfunction must have an estimated creatinine
clearance > 45 mL/min (based on Cockcroft-Gault equation)
• Investigators must confirm which TKI patient is to receive
• NOTE: Patients with known T315I mutation status should receive ponatinib
treatment
• For patients under age 70 and previously assigned to Arm C, intended chemotherapy
regimen must have been determined
• Step 3 (Re-Induction): Patients must have resolved any serious infectious
complications related to therapy
• Step 3 (Re-Induction): Any significant medical complications related to therapy must
have resolved
Exclusion Criteria:
• Patient must not have complaints of symptoms and/or have clinical and/or radiological
signs that indicate an uncontrolled infection or any other concurrent medical
condition that could be exacerbated by the treatment or would seriously complicate
compliance with the protocol
B Acute Lymphoblastic Leukemia With t(9,22)(q34.1,q11.2), BCR-ABL1, Lymphoid Leukemia, Leukemia
Testing Early Treatment for Patients With High-Risk Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL), EVOLVE CLL/SLL Study
This phase III trial compares early treatment with venetoclax and obinutuzumab versus delayed
treatment with venetoclax and obinutuzumab in patients with newly diagnosed high-risk chronic
lymphocytic leukemia or small lymphocytic lymphoma. Venetoclax is in a class of medications
called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by
blocking Bcl-2, a protein needed for cancer cell survival. Immunotherapy with monoclonal
antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and
may interfere with the ability of tumor cells to grow and spread. Starting treatment with the
venetoclax and obinutuzumab early (before patients have symptoms) may have better outcomes
for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma compared to
starting treatment with the venetoclax and obinutuzumab after patients show symptoms.
Priyanka Pophali
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04269902
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Inclusion Criteria:
• Participants must have a confirmed diagnosis of chronic lymphocytic leukemia (CLL) or
small lymphocytic lymphoma (SLL) (collectively referred to as CLL throughout)
according to the 2018 International Workshop on CLL. Participants must have been
diagnosed within 18 months prior to registration
• Participants must have CLL-International Prognostic Index (CLL-IPI) score >= 4 and/or
complex cytogenetics (defined as 3+ chromosomal abnormalities)
• Cytogenetic AND/OR FISH analyses must be completed at a Clinical Laboratory
Improvement Act (CLIA)-approved (or laboratories accredited under Accreditation Canada
Diagnostics to conduct FISH analyses) laboratory within 18 months prior to
registration. FISH panel should use probes to detect for abnormalities in chromosomes
13q, 12, 11q, and 17p
• TP53 mutation status from an next generation sequencing (NGS) test performed at any
CLIA-approved (or laboratories accredited under Accreditation Canada Diagnostics) lab
(if completed) must be obtained within 18 months prior to registration. This
sequencing test is distinct from FISH studies for del(17p)
• Immunoglobulin heavy chain locus variable (IgVH) mutational status from an NGS test
performed at any CLIA-approved lab (or laboratories accredited under Accreditation
Canada Diagnostics) must be obtained prior to registration (at any time prior to
registration)
• Serum beta-2 microglobulin level must be obtained within 28 days prior to registration
• Participants must not meet any of the IWCLL specified criteria for active CLL therapy
• Treatment with high dose corticosteroids and/or intravenous immunoglobulin for
autoimmune complications of CLL must be complete at least 4 weeks prior to enrollment
• Steroids used for treatment of conditions other than CLL/SLL must be at a dose of at
most 20 mg/day of prednisone or equivalent corticosteroid at the time of registration
• Prior therapy with anti CD20 monoclonal antibodies is not allowed
• Participants must not have received or be currently receiving any prior CLL-directed
therapy, including non-protocol-related therapy, anti-cancer immunotherapy,
experimental therapy (with exception of agents approved for emergency access use for
the prevention or treatment of COVID-19), or radiotherapy
• Participants must not be receiving or planning to receive any other investigational
agents before completing protocol therapy
• Participants must be >= 18 years of age
• Participants must have Eastern Cooperative Oncology Group (ECOG) performance status =<
2
• Platelet count >= 100,000/mm^3 within 28 days prior to registration
• Absolute neutrophil count (ANC) >= 1,000/mm^3 within 28 days prior to registration
• Creatinine clearance >= 30mL/min (by Cockcroft Gault) within 28 days prior to
registration
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 x upper
limit of normal (ULN) within 28 days prior to registration
• Total bilirubin =< 2.0 x ULN (or 5.0 x ULN if the participant has a history of
Gilbert's disease), within 28 days prior to registration
• Participants must be able to take oral medications
• Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
• Participants with history of malignancy are allowed providing the cancer has not
required active treatment within 2 years prior to registration (hormonal therapy is
permissible). The following exceptions are permissible: basal cell, squamous cell
skin, or non-melanomatous skin cancer, in situ cervical cancer, superficial bladder
cancer not treated with intravesical chemotherapy or Bacillus Calmette-Guerin (BCG)
within 6 months, localized prostate cancer requiring no more than chronic hormonal
therapy, or localized breast cancer requiring no more than chronic hormonal therapy
• Participants must not have current, clinically significant gastrointestinal
malabsorption, in the opinion of treating doctor
• Participants must not have cirrhosis
• Obinutuzumab has been associated with hepatitis reactivation. Participants must not
have uncontrolled active infection with hepatitis B or C. Participants with latent
hepatitis B infection must agree to take prophylaxis during and for 6 months following
active protocol therapy with V-O.
• Active infection with hepatitis B or C:
• Active infection is defined as detectable hepatitis B deoxyribonucleic acid
(DNA) or hepatitis C ribonucleic acid (RNA) by quantitative polymerase chain
reaction (PCR).
• Latent infection with hepatitis B:
• Latent infection is defined as meeting all of the following criteria:
• Hepatitis B surface antigen positive
• Anti-hepatitis B total core antibody positive
• Anti-hepatitis IgM core antibody undetectable
• Hepatitis B PCR undetectable
• Participants with latent hepatitis B infection must agree to take
prophylaxis with anti-hepatitis agents during and for 6 months following
active protocol therapy with V-O.
• Participants who have received intravenous immunoglobulin (IVIG) therapy
within 6 months who are hepatitis B core total antibody positive but PCR
undetectable are not mandated to take prophylaxis
• Participants must not have had major surgery within 30 days prior registration or
minor surgery within 7 days prior to registration. Examples of major surgery include
neurosurgical procedures, joint replacements, and surgeries that occur inside the
thoracic or abdomino-pelvic cavities. Examples of minor surgery include dental
surgery, insertion of a venous access device, skin biopsy, or aspiration of a joint.
If a participant has had a bone marrow biopsy for diagnosis or evaluation of CLL, this
will not exclude the patient from registration to the study. If there is a question
about whether a surgery is major or minor, this should be discussed with the Study
Chair
• Participants must not have known bleeding disorders (e.g., von Willebrand's disease or
hemophilia)
• Participants must not have a history of stroke or intracranial hemorrhage within 6
months prior to enrollment
• Participants must not require continued therapy with a strong inhibitor or inducer of
CYP3A4/5, as venetoclax is extensively metabolized by CYP3A4/5
• Participants must not have uncontrolled autoimmune hemolytic anemia or idiopathic
thrombocytopenia purpura
• Participants must not have any currently active, clinically significant cardiovascular
disease, such as uncontrolled arrhythmia or class 3 or 4 congestive heart failure as
defined by the New York Heart Association Functional Classification
• Participants must not have a history of myocardial infarction, unstable angina, or
acute coronary syndrome within 6 months prior to enrollment
• Participants must not be pregnant or nursing, as there are no safety data available
for these drug regimens during pregnancy. Women/men of reproductive potential must
have agreed to use an effective contraceptive method. A woman is considered to be of
"reproductive potential" if she has had 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
• Participants must agree to have specimens submitted for translational medicine (MRD)
and specimens must be submitted as outlined
• Participants must be offered participation in banking for future research. With
patient's consent, specimens must be submitted as outlined
• Participants who are able to complete patient reported outcome (PRO) forms in English,
Spanish, French, German, Russian or Mandarin must agree to participate in the quality
of life assessments. (Those participants who are unable to read and write in English,
Spanish, French, German, Russian or Mandarin may be registered to S1925 without
contributing to the quality of life portion of the study.)
• Participants 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
• NOTE: 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
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Lymphoid Leukemia, Leukemia
Pilot Study of Imatinib Cetuximab Combo for H & N Cancer
The goal of this clinical trial is to find if levels of a protein called AXL in tumor cells
relate to how tumors respond to cetuximab (CTX) combined with imatinib in participants with
head and neck cancer. This interventional study will occur in the time between diagnosis of
your cancer and surgery to remove your tumor or radiation or chemoradiation treatment of your
primary cancer.
Participants will undergo a research blood draw and a research biopsy as part of the
screening process, and will be in this research study for approximately 13 to 16 months.
Justine Bruce, MD
All
18 Years and over
Early Phase 1
This study is NOT accepting healthy volunteers
NCT05816785
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Inclusion Criteria:
• Age > 18 years at the time of consent.
• Histological confirmation of squamous cell carcinoma of the head and neck.
• For those patients with oropharyngeal cancer, subjects must have either
• HPV-negative status by p16 expression or HPV-DNA Expression.
• HPV-positive status by p16 expression AND a >10 pack year smoking history.
• Subjects must be appropriate candidates for definitive curative intent treatment,
either via surgical resection, definitive radiation therapy alone, or definitive
concurrent chemoradiation therapy.
• For the screening research biopsy, subjects must have sufficient tumor volume
(approximately 10 cc) to accommodate at minimum 2-3 core samples for the research
biopsy.
• For the post-treatment (CTX/Imatinib) research biopsy, subjects who are scheduled to
receive definitive radiation therapy (+/- concurrent chemotherapy) are required to
have sufficient tumor volume to accommodate at minimum 2-3 core samples for the
research biopsy.
• Demonstrate adequate organ function; all screening labs to be obtained within 28 days
prior to registration.
Exclusion Criteria:
• Subjects with a diagnosis of nasopharyngeal carcinoma, advanced cutaneous squamous
cell carcinoma of the head and neck, or salivary gland tumors are excluded from this
study.
• Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.
active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable
safety risks or compromise compliance with the protocol.
• Prior chemotherapy, radiotherapy, or major surgery within 8 weeks of study enrollment
or those who have not recovered (to grade ≤ 1 or baseline) from clinically significant
adverse events due to agents administered more than 8 weeks earlier (alopecia and
fatigue excluded). Clinical significance to be determined by the study investigator.
• Subjects who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study.
• Subjects who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to imatinib or CTX.
Head and Neck Cancer, Squamous Cell Carcinoma of Head and Neck, Lip, Oral Cavity and Pharynx, Esophagus, Head and Neck
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