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.
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
Lymphoid Leukemia, Leukemia, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
A Study to Assess the Efficacy and Safety of Daily OM-85 in Young Children With Recurrent Wheezing
This study will assess the efficacy and safety of daily OM-85 treatment compared to placebo
in children aged 6 months to 5 years with recurrent wheezing
Daniel Jackson
All
6 Months to 72 Months old
Phase 2
This study is NOT accepting healthy volunteers
NCT05857930
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Inclusion Criteria:
Subjects who meet all the following criteria will be included in the study:
• Children of either gender, aged between 6 and 72 months (5 years inclusive).
• Children with recurrent wheezing:
• For ICS/LTRA naïve patients or intermittent users (patients using ICS treatment
only during an upper RTI to prevent WE): ≥2 WEs including at least 1 severe
episode (i.e., treated with OCS OR having triggered an ED visit/hospitalization),
OR ≥3 WEs including at least one that triggered an unscheduled physician visit,
in the 12 months prior to enrollment.
• For ICS/LTRA daily users: ≥1 severe WE (i.e., treated with OCS OR having
triggered an ED visit/hospitalization) OR ≥2 WEs including at least one that
triggered an unscheduled physician visit, as reported by parents or LAR of
subject (i.e., guardians), in the 12 months prior to enrollment, while being on
their daily controller therapy.
• Up-to-date vaccination status as per applicable State Vaccination Requirements for
school/day-care entry.
• Parents or LAR have provided the appropriate written informed consent. Written
informed consent must be provided before any study-specific procedures are performed
including screening procedures.
Note: If a subject is experiencing respiratory symptoms at time of screening, he/she could
only be randomized once symptoms have resolved for at least one week.
Exclusion Criteria:
• Known anatomic alterations of the respiratory tract.
• Wheezing documented to be caused by gastroesophageal reflux.
• Other known chronic respiratory diseases (e.g., tuberculosis or cystic fibrosis).
• Any known autoimmune disease.
• Known human immunodeficiency virus (HIV) infection or any known type of congenital or
iatrogenic immune deficiency (including immunoglobulin (Ig) A deficiency).
• Known acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or
renal function abnormalities.
• Children born prematurely i.e., before 34 weeks of gestational age.
• Children with an abnormally low or high weight for their age and height, if this would
not allow safe completion of the clinical study in the opinion of the investigator.
• Any known neoplasia or malignancy.
• Treatment with the following medications:
• Systemic (intravenous or intramuscular) or OCS (e.g., oral prednisolone) within 4
weeks before study enrollment.
• Previous and/or concomitant immunosuppressants, immunostimulants, or gamma
globulins within 6 months before study enrollment.
• Any major surgery within the last 3 months prior to study enrollment.
• Known allergy or previous intolerance to investigational drug.
• Any other clinical conditions, which in the opinion of the Investigator, would not
allow safe completion of the clinical study.
• Other household members have previously been randomized in this clinical study.
• Inability to comply with the study requested visit schedule (e.g., expected relocation
within 12 months of the screening for the study).
• Currently enrolled in or has completed any other investigational device or drug study
<30 days prior to screening or receiving other investigational agent(s).
Note: Subjects with past, present, or at risk of COVID-19 should not be excluded from the
study.
The objective of this project is to determine if mTORC1 inhibition by 24 weeks of daily (0.5
mg/day) or weekly (5 mg/week) everolimus can safely improve physiological and molecular
hallmarks of aging in humans. Participants who are 55-80 years old and insulin resistant or
prediabetic will be randomized to treatment and can expect to be on study for up to
approximately 38 weeks. Participants aged 18-35 will not receive the intervention and can
expect to be on study for up to approximately 8 weeks.
Adam Konopka
All
18 Years to 80 Years old
Phase 2
This study is also accepting healthy volunteers
NCT05835999
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Inclusion Criteria:
Adults aged 55-80 years old
• Free of overt chronic disease
• Willing to provide informed consent
• Willing to comply with all study procedures and be available for the duration of the
study
• Able to use and be contacted by the telephone
• Ability to take oral medication
• Insulin Resistant defined by HOMA-IR greater than or equal to 1.5 or prediabetic
defined as:
• impaired fasting glucose (100-125 mg/dL)
• HbA1c (5.7-6.4 percent)
• glucose 2 hours after a 75 gram oral glucose tolerance test (140-199 mg/dL)
• previous diagnosis of prediabetes in the past year
• Not planning to change diet or physical activity status
• Adequate organ function as indicated by standard laboratory tests: hematology
(complete blood count), clinical chemistry and urinalysis
• Females of childbearing potential must have a negative urine pregnancy test before
DEXA and before the oral glucose tolerance test (OGTT). A female of child-bearing
potential is any woman (regardless of sexual orientation, having undergone a tubal
ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,
has had menses at any time in the preceding 12 consecutive months)
• Women of childbearing potential in sexual relationships with men must use an
acceptable method of contraception from 30 days prior to enrollment until 4 weeks
after completing study visits. Males must agree to avoid impregnation of women during
and for four weeks after completing study visits through use of an acceptable method
of contraception.
• Note: Includes, but is not limited to, barrier with additional spermicidal foam
or jelly, intrauterine device, hormonal contraception (started at least 30 days
prior to study enrollment), intercourse with men who underwent vasectomy.
• Pregnancy or breastfeeding
• Heart disease
• Cerebrovascular disease
• Cancer or less than 5 years in remission
• Chronic respiratory disease
• Chronic liver disease
• Diabetes
• Alzheimer's
• Chronic kidney disease
• Problems with bleeding, on medication that prolongs bleeding time (if subject cannot
safely stop prior to biopsy)
• Taking strong or moderate CYP3A4 and/or P-glycoprotein (PgP) inhibitors
• Taking strong CYP3A4 activators
• Subjects who are not willing to restrict the use of grapefruit, grapefruit juice, and
other foods that are known to inhibit cytochrome P450 and PgP activity and may
increase everolimus exposures and should be avoided during treatment
• Subjects who are not willing to restrict the use of St. John's Wort (Hypericum
perforatum) because it may decrease everolimus exposure unpredictably
• Subjects who are not willing to avoid blood donations 8 weeks prior to the first visit
and 8 weeks after the last visit
• Contraindications with MRI which could include metal on your body
• Low white-blood cell count (<4,000 cell/µL)
• History of stomatitis or ulcers in the mouth
• Those on glucose lowering drugs
• Participating in intensive exercise training program (high to moderate intensity
exercise greater than 150 minutes per week) or planning to start new exercise program
during study period
• Tobacco use
• Allergies to lidocaine or everolimus
• Subjects currently enrolled in other clinical trials. Subjects may be eligible after a
washout period that will be reviewed on a case by case basis.
• Individuals with limited English proficiency
The objective of RAP PAC is to identify safe and effective weekly dose(s) for the mTOR
inhibitors sirolimus and everolimus that intervene on the underlying fundamental biology of
aging. Participants who are 55-89 years old that are free of overt chronic diseases will be
assigned to either 6 weeks of sirolimus or everolimus (5 mg, 10 mg, or 15 mg once per week).
The investigators will complete the everolimus arm first and then subsequently complete the
sirolimus arm of the study. Total time on study would be up to 17 weeks to complete baseline
and follow up visits.
Adam Konopka
All
55 Years to 89 Years old
Phase 1
This study is also accepting healthy volunteers
NCT05949658
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Inclusion Criteria:
• Middle-age adults free of overt chronic disease
• Willing to provide informed consent
• Willing to comply with all study procedures and be available for the duration of the
study
• Able to use and be contacted by telephone
• Ability to take oral medication
• Not planning to change diet or physical activity status
• Adequate organ function as indicated by standard laboratory tests: hematology
(complete blood count), and clinical chemistry
• Males must agree to avoid impregnation of women during and for four weeks after
completing study visits through use of an acceptable method of contraception
Exclusion Criteria:
• Heart disease (history, abnormal ECG)
• Cerebrovascular disease (history)
• Cancer or less than 5 years in remission (history)
• Chronic respiratory disease (history, FEV1/FVC < 70, FEV1 < 80% predicted)
• Chronic liver disease (history, abnormal blood liver panel, ALT >104 IU/L, AST >80
IU/L)
• Diabetes (history, HbA1C ≥ 6.5, fasting blood glucose≥126 mg/dl, OGTT ≥ 200 mg/dl at 2
hrs.)
• Alzheimer's (history)
• Chronic kidney disease (history, abnormal blood kidney panel including serum
creatinine>1.4, eGFR≤60 ml/min/1.73m2)
• Problems with bleeding, on medication that prolongs bleeding time (if subject cannot
safely stop prior to biopsy)
• Taking azathioprine (Imuran), cyclosporine (Gengraf, Neoral, Sandimmune),
dexamethasone (Decadron, Dexpak), methotrexate (Rheumatrex, Trexall), prednisolone
(Orapred, Pediapred, Prelone), prednisone (Sterapred), sirolimus (Rapamune), and
tacrolimus (Prograf) or other medications proposed to lower the immune system
• Taking strong or moderate CYP3A4 and/or P-glycoprotein (PgP) inhibitors such as
ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir,
telithromycin, ritonavir, indinavir, nelfinavir, voriconazole, amprenavir,
fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem
• Taking strong CYP3A4 activators such as phenytoin, carbamazepine, rifampin, rifabutin,
rifapentine, phenobarbital
• Subjects who are not willing to restrict the use of grapefruit, grapefruit juice,
cannabidiol (CBD) and other foods/substances that are known to inhibit cytochrome P450
and PgP activity and may increase everolimus exposures and should be avoided during
treatment
• Subjects who are not willing to restrict the use of St. John's Wort (Hypericum
perforatum) because it may decrease everolimus exposure unpredictably.
• Subjects who are not willing to avoid blood donations 8 weeks prior to the first visit
and 8 weeks after the last visit
• Low white-blood cell count (<4,000 cell/µL)
• History of stomatitis or ulcers in the mouth
• Those on glucose lowering drugs
• Participating in intensive exercise training program (high to moderate intensity
exercise greater than 150 minutes per week) or planning to start new exercise program
during study period
• Tobacco use
• Allergies to lidocaine, sirolimus, or everolimus
• Subjects currently enrolled in other clinical trials. Subjects may be eligible after a
washout period that will be reviewed on a case-by-case basis.
• Individuals with limited English proficiency
• Subjects who are planning to have elective surgery 12 weeks prior to or during the
intervention
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
The goal of this observational study is to determine the feasibility of renal Near Infrared
Spectroscopy (NIRS) monitoring in the newborn nursery for newborns at low risk of coarctation
of the aorta (CoA). The main questions it aims to answer are:
- whether continuous renal NIRS monitoring is feasible;
- whether NIRS monitoring results in higher nursing and parent/caregiver satisfaction than
current standard monitoring; and,
- whether participants who develop CoA will spend a smaller proportion of time within the
normal range than patients who do not have CoA.
Participants will be observed through continuous renal oxygenation monitoring with NIRS.
Matthew Harer, MD
All
15 Years and over
Pilot/Feasibility
This study is NOT accepting healthy volunteers
NCT05842876
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Neonate
Inclusion Criteria:
• Delivered at ≥ 35 weeks of gestation
• <12 hours of age
• Inpatient at Meriter Hospital, Inc. NICU or Newborn Nursery or AFCH PICU or NICU
• Diagnosed as at risk for CoA
Neonate
Exclusion Criteria:
• Major congenital anomalies of the kidney
• Attending physician's discretion to not place sensors due to clinical concerns
• In the researcher's medical opinion, there is a significant likelihood that the
neonate would not survive the first 3 days of life
Primary Caregiver
Inclusion Criteria:
• Able to understand and the willing to sign a written informed consent document
• Willing to comply with all study procedures and be available for the duration of the
study
• Birth parent (i.e., the parent who gave birth to the baby) who is the primary
caregiver of a neonate who is eligible to participate in study
• Agrees to enroll neonate into study
• Aged 15 years or older
• Pregnant mother with a baby diagnosed prenatally as at risk for CoA will be eligible
for the study. They must also meet the following criteria:
• Require an "arch watch care plan" as a results of prenatal ultrasonography findings
• Agree to enroll offspring into the study at birth
Primary Caregiver
Exclusion Criteria:
• Subject is unable to provide informed consent, including subjects who are in foster
care and subjects within state custody
• Pregnant woman who does not plan to maintain custody of the child after birth, such as
instances of adoption or surrogacy
Newborn Nursery Nursing Staff:
• All Newborn Nursery nursing staff at Meriter Hospital, Inc.'s Newborn Nursery are
eligible to participate
Study of Cabozantinib and Nivolumab in Metastatic Castration Resistant Prostate Cancer (CANOPY)
This is a multicenter, single-arm, two-stage open-label phase 2 study of the combination of
cabozantinib + nivolumab in subjects with advanced castration-resistant prostate cancer
(CRPC).
Christos Kyriakopoulos, MD
Male
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05502315
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Inclusion Criteria:
Subjects must meet all of the following applicable inclusion criteria to participate in
this study:
• Willing and able to provide, or have a legally authorized representative provide,
written informed consent and HIPAA authorization for the release of personal health
information. A signed informed consent must be obtained before screening procedures
are performed. NOTE: HIPAA authorization may be either included in the informed
consent or obtained separately.
• Males 18 years of age and above.
• Histological or cytological proof of prostate adenocarcinoma.
• ECOG status of ≤ 2
• Progressive mCRPC as defined: 1) castrate levels of serum testosterone < 50 ng/dL AND
2) progressive disease as defined by PSA or radiographic progression. Subjects with
measurable and non-measurable disease (i.e., bone only metastases) are allowed. NOTE:
ENROLLMENT of subjects with non-measurable disease (i.e., bone only metastases) will
be capped at 50% of enrollment target (n=25).
• Must have exposure to one prior taxane (or be taxane ineligible or refuse taxane) AND
one prior AR-targeting agent (for example, abiraterone, enzalutamide, apalutamide,
darolutamide). Receipt of taxane or AR-targeting agent may be in the hormone sensitive
or castration resistant setting.
• Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior
treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive
therapy.
• Normal organ function with acceptable initial laboratory values within 14 days of
treatment start:
• WBC: ≥ 2,500/mcL
• ANC: ≥ 1,500/mcL
• Hemoglobin: ≥ 9 g/dL (transfusions are permitted)
• Platelet count: ≥ 100,000/mcL
• Serum creatinine or calculated Creatinine Clearance: Serum creatinine ≤ 1.5 x ULN
or calculated CrCl ≥ 30 mL/min as defined by Cockcroft-Gault equation
• Total Bilirubin: ≤ 1.5 x ULN (≤ 3 x ULN for subjects with documented Gilbert's
disease)
• SGOT (AST): ≤ 3 x ULN
• SGPT (ALT): ≤ 3 x ULN
• Alkaline Phosphatase (ALP): ≤ 5 x ULN with documented bone metastases
• Serum Albumin: ≥ 2.8 g/dL
• Urine protein/creatinine ratio (UPCR): ≤ 2 mg/mg (≤ 113.2 mg/mmol), or 24-h urine
protein ≤ 2 g
• Subjects must agree to use a medically acceptable method of birth control as outlined
in the protocol
• HIV-positive with negative viral loads on stable antiretroviral regimen will be
considered eligible. Subjects must have CD4 count > 350.
Exclusion Criteria:
Subjects meeting any of the criteria below may not participate in the study:
• Small cell or neuroendocrine component or histology.
• Prior cabozantinib or checkpoint inhibitor.
• Receipt of any type of small molecule kinase inhibitor (including investigational
kinase inhibitor) within 2 weeks before first dose of study treatment.
• Receipt of any type of cytotoxic, biologic or investigational systemic anti-cancer
agent within 4 weeks before first dose of study treatment.
• Treatment with abiraterone, apalutamide, or darolutamide within 2 weeks of treatment
initiation. Treatment with investigational prostate cancer directed therapy within 4
weeks of treatment initiation. Treatment with enzalutamide within 4 weeks of treatment
initiation.
• Receipt of more than 1 line of chemotherapy (including both hormone sensitive and
CRPC). First-generation anti-androgen use (such as bicalutamide) will not be tabulated
as a line of therapy.
• Administration of a live, attenuated vaccine within 30 days prior to first dose of
study treatment.
• Active autoimmune disease or condition requiring prednisone >10 mg daily (or
equivalent). Physiologic replacement is permitted. Topical, ocular, intra-articular
steroids or inhaled corticosteroids are permitted.
• Imminent or established spinal cord compression based on clinical and/or imaging
findings.
• Radiation therapy within 1 week of study treatment start.
• Known brain metastases or cranial epidural disease unless adequately treated with
radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks
prior to first dose of study treatment.
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest CT scan.
• Malabsorption syndrome.
• Requirement for hemodialysis or peritoneal dialysis.
• History of solid organ or allogenic stem cell transplant.
• Active hepatitis B/C or positive TB test with active mycobacterial infection requiring
systemic treatment.
• Active treatment (within 5 days of registration) with coumarin agents (e.g.,
warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor
betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the
following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable
guidelines) and low-dose molecular weight heparins (LMWH).
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors
rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who
are on a stable dose of the anticoagulant for at least 1 week before first dose
of study treatment without clinically significant hemorrhagic complications from
the anticoagulation regimen or the tumor.
• The subject has uncontrolled, significant intercurrent or recent illness including,
but not limited to, the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class 3 or 4, unstable
angina pectoris, serious cardiac arrhythmias.
• Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm
Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive
treatment.
• Stroke (including transient ischemic attack [TIA]), myocardial infarction
(MI), or other ischemic event, or thromboembolic event (e.g., deep venous
thrombosis, pulmonary embolism) within 6 months before first dose of study
treatment.
• Subjects with a diagnosis of incidental, subsegmental PE or DVT within 6
months are allowed if stable, asymptomatic, and treated with a stable dose
of permitted anticoagulation (see exclusion criterion above) for at least 1
week before first dose of study treatment.
• Gastrointestinal (GI) disorders including those associated with a high risk of
perforation or fistula formation
• The subject has evidence of tumor invading the GI tract, active peptic ulcer
disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis,
cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis,
acute obstruction of the pancreatic duct or common bile duct, or gastric
outlet obstruction.
• Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal
abscess within 6 months before first dose of study treatment. Note: Complete
healing of an intra-abdominal abscess must be confirmed before first dose of
study treatment.
• Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon
(2.5ml) of red blood, or other history of significant bleeding (e.g., pulmonary
hemorrhage) within 12 weeks before first dose of study treatment.
• Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease
manifestation.
• Lesions invading or encasing any major blood vessels.
• Other clinically significant disorders that would preclude safe study
participation.
• Serious non-healing wound/ulcer/bone fracture.
• Uncompensated/symptomatic hypothyroidism.
• Moderate to severe hepatic impairment (Child-Pugh B or C).
• Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of
brain metastasis) within 2 weeks before first dose of study treatment. Minor
surgeries within 10 days before first dose of study treatment. Subjects must have
complete wound healing from major surgery or minor surgery before first dose of
study treatment. Subjects with clinically relevant ongoing complications from
prior surgery are not eligible.
• Corrected QT interval calculated by Fridericia formula (QTcF) >500 ms per
electrocardiogram (ECG) within 14 days before first dose of study treatment [add
reference for Fridericia formula]. NOTE: If a single ECG shows a QTcF with an
absolute >500 ms, two additional ECGs at intervals of approximately 3 min must be
performed within 30 min after the initial ECG, and the average of these three
consecutive results for QTcF will be used to determine eligibility.
• Any other active malignancy at time of first dose of study treatment or diagnosis
of another malignancy within 3 years prior to first dose of study treatment that
requires active treatment, except for locally curable cancers that have been
apparently cured, such as basal or squamous cell skin cancer or superficial
bladder cancer.
• Known allergy to any of the compounds under investigation.
• Inability to swallow tablets.
Prostate, Castration-resistant Prostate Cancer, Metastatic Cancer
TRAQinform Assessment of Immunotherapy Response (AIQ TRAQinform)
The intent of this study is to evaluate the actionable information output from the TRAQinform
Immuno technology in a prospective, non-interventional clinical study. Subjects with
metastatic melanoma treated with standard of care (SOC) dual-agent immunotherapy will be
enrolled. Subjects will receive SOC immunotherapy monitored for treatment response with FDG
PET/CT's at baseline (SOC), after 3-4 weeks of treatment (non-SOC) and 12 at weeks of
treatment (SOC).
Vincent Ma, MD
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT05819255
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Inclusion Criteria:
• Diagnosis of metastatic melanoma and is planned to start or has received one cycle of
treatment with standard of care, dual-agent immunotherapy.
• Previous adjuvant anti-PD-I monotherapy is allowed. Patients must be greater than 6
months from the last treatment.
• Previous adjuvant BRAF/MEK therapy is allowed.
• Ability to tolerate 3 FDG PET/CT procedures. One at baseline, prior to the start of
the combination immuno therapy, after 3 •4 weeks of the combination immunotherapy
treatment, and at 12 weeks of the combination treatment.
• Estimated life expectancy of greater than 12 months at screening.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at
screening.
• Deemed suitable for starting standard of care combination immunotherapy for metastatic
melanoma.
• Willing and able to provide informed consent for FDG PET/CT imaging.
Exclusion Criteria:
• Any concurrent disease, infection, or comorbid condition that interferes with the
ability of the patient to participate in the trial; places the patient at undue risk;
or complicates the interpretation of the data, in the opinion of the investigator.
• A second malignancy
• Pregnancy or women who are breast feeding
Study to Evaluate the Safety and Efficacy of Oral NRC-2694-A in Combination With Paclitaxel in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma, Who Progressed on or After Immune Checkpoint Inhibitor Therapy
This is a Phase 2, open-label, multicenter, single-arm study of NRC-2694-A in combination
with paclitaxel in patients with R/M HNSCC with progression on or after ICI therapy.
A total of approximately 46 male and female patients will be enrolled. This sample size is
based on Simon's 2-stage design with historical control ORR of 30% and a target ORR of 50%.
Justine Bruce, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05283226
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Inclusion Criteria:
• Is willing and capable of understanding the written informed consent, provides signed
and witnessed written informed consent, and agrees to comply with protocol
requirements.
• Is male or female aged 18 years or older at the time of consent.
• Has histologically confirmed unresectable R/M HNSCC (oral cavity, oropharynx,
hypopharynx, and larynx).
• Has documented radiographical progressive disease assessed by the principal
investigator per RECIST v1.1.
• Has a measurable lesion per RECIST v1.1.
• Has ECOG performance status score of ≤2.
• Must have progressed during or after receiving ICI therapy, such as pembrolizumab or
nivolumab. Patients with prior immune-mediated reactions due to ICI therapies (eg,
pembrolizumab or nivolumab) and who had recovered prior to study entry will also be
eligible.
• Female patients of childbearing potential should have a negative urine test before
enrollment. If the urine pregnancy test is positive or gives equivocal results, a
serum pregnancy will be required for confirmation.
• Patients of reproductive age must use acceptable methods of contraception throughout
the study period and for 30 days following the last dose of investigational product
(see protocol for further guidance).
• During screening and at subsequent visits, the investigator should ensure adequate
bone marrow reserve (neutrophil count ≥1500/mm3, platelet count ≥100,000/mm3, and
hemoglobin level 8.0 g/dL), renal function (creatinine clearance ≥50 mL/min calculated
by Cockcroft-Gault formula), liver function (total bilirubin level ≤1.5 × ULN [except
patients with documented Gilbert's syndrome] and serum transaminase levels ≤2.5 × ULN
or ≤5 × ULN for liver metastasis and/or obstructive jaundice).
• Must have completed a duration of at least 4 weeks after stopping ICI therapy and must
have recovered to grade ≤1 from all toxicities due to this therapy.
Exclusion Criteria:
• Has cardiac, hepatic, endocrine, pulmonary, or autoimmune disease, interstitial lung
disease, renal or psychiatric disorders, not controlled with therapy corresponding to
the illness or a condition that contraindicates the use of a taxane or an EGFR
inhibitor.
• Has uncontrolled brain metastases. Patients are allowed if brain metastasis has been
previously treated with surgery, whole brain irradiation, and/or stereotactic
radiosurgery and are considered controlled (controlled by the dose ≤10 mg/day of
prednisone or equivalent) at the time of the first dose of investigational product.
Radiological evaluation of brain metastasis will be performed only if the patient has
symptoms. For asymptomatic patients, brain imaging during screening is not required.
• Has baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTc
interval >480 milliseconds [CTCAE Grade 1] using Fredericia's QT correction formula).
• Has a history of additional risk factors for Torsade de pointes (eg, heart failure,
hypokalemia, family history of long QT syndrome).
• Has had prior cetuximab therapy for recurrent or metastatic disease. Note that
cetuximab used concomitantly with radiotherapy or as an induction therapy is
acceptable
• Has received any other EGFR-targeted therapies for recurrent or metastatic disease.
• Currently participating in any clinical trial or receiving investigational therapy on
expanded access or compassionate basis.
• Has nasopharyngeal carcinomas or salivary gland cancers.
• Has received investigational products or any other salvage therapy after failure of
pembrolizumab/nivolumab therapy.
• Female patient who tested positive for pregnancy.
• Female patient who is breastfeeding or planning to become pregnant, or male patient
planning to father a child within the duration of the study.
• Has tested positive for HIV, HBsAg, HCV antibody, or HCV RNA at screening. However,
patients who test positive for HCV antibody, but negative for HCV RNA, will be
allowed. In addition, patients with controlled HIV, chronic HBV on suppressive
antiviral therapy, or a history of HCV infection status post-curative antiviral
treatment with an HCV viral load below limit of quantification are permitted to
participate (DHHS 2020).
• Has active infection requiring intravenous anti-infective therapy within 7 days prior
to Day 1 Cycle 1 or is febrile due to infection.
• Has had major surgery within 4 weeks prior to screening.
• Administered a live attenuated vaccine within 4 weeks prior to Day 1 Cycle 1 or
anticipation that such a live attenuated vaccine will be required during the study.
• Has known or suspected hypersensitivity to any components of the formulation used for
this investigational product.
• Has concurrent disease or any clinically significant abnormality following the
investigator's review of the screening physical examination findings, 12-lead ECG
results, and clinical laboratory tests, which in the judgment of the investigator
would interfere with the patient's participation in this study or evaluation of study
results.
• Unable to come for study visits per schedule.
• Has current drug or alcohol abuse.
• Has received prior treatment with paclitaxel or docetaxel for metastatic or recurrent
HNSCC. However, prior paclitaxel or docetaxel as a component of a curatively-intended
multimodality treatment for locally advanced HNSCC is permitted.
Carcinoma, Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma, Lip, Oral Cavity and Pharynx, Head and Neck
Randomized Study in Children and Adolescents With Migraine: Acute Treatment
The purpose of this study is to test the safety and efficacy of BHV-3000 versus placebo in
the acute treatment of moderate or severe migraine in children and adolescents.
Ali Zandieh
All
6 Years to 17 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04649242
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Inclusion Criteria:
1. History of migraine (with or without aura) for > 6 months before Screening according
to the IHS Classification ICHD-319 specifications for pediatric migraine. History may
be verified using both medical records and recall by the participant and/or
participant's parent(s)/legal representative(s).
2. History of 1 to 8 moderate or severe attacks per month during the 2 months prior to
enrollment, with attacks lasting > 3 hours without treatment, and attacks occurring at
intervals > 24 hours.
3. Prophylactic migraine medication are permitted if the dose has been stable for at
least 12 weeks prior to the Baseline Visit, and the dose is not expected to change
during the course of the study.
1. Participants may remain on one (1) medication with possible migraine prophylactic
effects, excluding CGRP antagonists [biologic or small molecule], during the
treatment phases.
2. Concomitant use of a CGRP antagonist, such as erenumab or fremanezumab, is
prohibited.
3. Previously discontinued prophylactic migraine medication must have done so at
least 90 days prior to the Screening Visit.
4. Verbally distinguish between migraine and other types of headaches.
5. Participants must have a weight > 40 kg at the Screening Visit.
6. Adequate venous access for blood sampling.
7. Male and female participants ≥ 6 to < 18 years of age (participants must not reach
their 18th birthday during the study).
Exclusion Criteria:
1. History of cluster headache or hemiplegic migraine headache.
2. Confounding and clinically significant pain syndrome that may interfere with the
participant's ability to participate in this study.
3. Current psychiatric condition that is uncontrolled and/or untreated for a minimum of 6
months prior to the Screening Visit. Participants with a lifetime history of psychosis
and/or mania.
4. History of suicidal behavior or major psychiatric disorder.
5. Current diagnosis or history of substance abuse; positive drug test at Screening.
6. History of moderate or severe head trauma or other neurological disorder (including
seizure disorder) or systemic medical disease that is likely to affect central nervous
system functioning.
7. Recent or planned surgery, requiring general anesthesia, <8 weeks prior to the
Screening Visit.
8. Participant has had gastrointestinal surgery that interferes with physiological
absorption and motility (i.e., gastric bypass, duodenectomy, or gastric banding).
9. Current diagnosis of viral hepatitis or a history of liver disease.
10. Conditions considered clinically relevant in the context of the study such as
uncontrolled hypertension (high blood pressure), diabetes, a life-threatening allergy
Long-term Safety Study of Rimegepant in Pediatric Subjects for the Acute Treatment of Migraine
The purpose of this study is to test the long-term safety of rimegepant in the acute
treatment of moderate or severe migraine in children and adolescents (≥ 6 to < 18 years of
age).
Ali Zandieh
All
6 Years to 17 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04743141
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Inclusion Criteria:
1. History of migraine (with or without aura) for ≥ 6 months before Screening
2. History of 1 to 8 moderate or severe attacks per month during the 2 months prior to
enrollment.
3. 1 or more migraine days requiring treatment during the Observation Phase.
4. Prophylactic migraine medication is permitted if the dose has been stable for at least
12 weeks prior to the Baseline Visit
5. Ability to distinguish between migraine and other types of headaches.
6. Weight ≥ 40 kg at the Screening Visit.
7. Adequate venous access for blood sampling.
8. Male and female participants ≥ 6 to < 18 years of age (participants must not reach
their 18th birthday before enrollment into the study)
Exclusion Criteria:
1. History of cluster headache or hemiplegic migraine headache.
2. Confounding and clinically significant pain syndrome
3. Current uncontrolled and/or untreated psychiatric condition for a minimum of 6 months
prior to the Screening Visit (lifetime history of psychosis and/or mania are
excluded).
4. History of suicidal behavior or major psychiatric disorder.
5. Current diagnosis or history of substance abuse; positive drug test at Screening.
Acute Treatment of Migraine, Other, Brain & Neurological
A Study of Baricitinib (LY3009104) in Children From 6 Years to Less Than 18 Years of Age With Alopecia Areata (BRAVE-AA-PEDS)
The main purpose of this study is to determine the efficacy and safety of baricitinib for the
treatment of severe or very severe alopecia areata (hair loss) in children from 6 years to
less than 18 years of age.
The study is divided into 4 periods, a 5-week Screening period, a 36-week Double-Blind
Treatment Period, an approximately 2-year Long-term Extension Period, and a 4-week
Post-treatment Follow-up period.
Lisa Arkin
All
6 Years to 17 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT05723198
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Inclusion Criteria:
• Enrollment will be fully sequential by age group, with adolescents (12 to less than 18
years old) enrolling before children (6 to less than 12 years old).
• Have severe areata alopecia (AA) for at least 1 year
• Diagnosis for at least 1 year
• Current AA episode of at least 6 months' duration
• SALT score ≥50% at screening and baseline
• History of trial and failure with at least 1 available treatment (topical or other)
for AA
• History of psychological counseling related to AA
• Current episode of severe AA of less than 8 years.
• Note: Participants who have severe AA for ≥8 years may be enrolled if episodes of
regrowth, spontaneous or under treatment, have been observed on the affected
areas over the past 8 years.
Exclusion Criteria:
• Primarily "diffuse" type of AA (characterized by diffuse hair shedding).
• Are currently experiencing other forms of alopecia including, but not limited to
trichotillomania, telogen effluvium, chemotherapy-induced hair loss, or any other
concomitant conditions (for example, tinea capitis, psoriasis, lupus erythematosus, or
secondary syphilis) that would interfere with evaluations of the effect of study
medication on AA.
• Are largely or wholly incapacitated permitting little or no self-care, such as being
bedridden
• Have uncontrolled arterial hypertension
• Have had major surgery within 8 weeks prior to screening or will require major surgery
during the study
• Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal,
endocrine, hematological, neurological, or neuropsychiatric disorders or any other
serious and/or unstable illness that, in the opinion of the investigator, could
constitute an unacceptable risk when taking IP or interfere with the interpretation of
data.
• Have a positive test for hepatitis B virus (HBV) infection
• Have hepatitis C virus (HCV) infection (positive for anti hepatitis C antibody with
confirmed presence of HCV ribonucleic acid [RNA]).
• Have evidence of human immunodeficiency virus (HIV) infection and/or positive HIV
antibodies.
Prospective Clinical Assessment Study in Children With Achondroplasia (ACH)
This is a long-term, multi-center, observational study in children 2.5 to <17 years with
achondroplasia (ACH). The objective is to evaluate growth, ACH-related medical complications,
assessments of health-related quality of life, body pain, functional abilities, cognitive
functions, and treatments of study participants. No study medication will be administered.
Janet Legare
All
30 Months to 17 Years old
N/A
This study is NOT accepting healthy volunteers
NCT04035811
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Key
Inclusion Criteria:
• Signed informed consent by study participant or parent(s) or legally authorized
representative (LAR) and signed informed assent by the study participant (when
applicable)
• Aged 2.5 to <17 years at study entry
• Diagnosis of ACH
• Study participants and parent(s) or LAR(s) are willing and able to comply with study
visits and study procedures
Key
Exclusion Criteria:
• Have hypochondroplasia or short stature condition other than ACH (e.g. trisomy 21,
pseudoachondroplasia, psychosocial short stature)
• In females, having had their menarche
• Height < -2 or > +2 standard deviations for age and sex based on reference tables on
growth in children with ACH
• Annualized height growth velocity ≤1.5 cm/year over a period ≥6 months prior to
screening
• Have a concurrent disease or condition that in the view of the Investigator and/or
Sponsor, may impact growth or where the treatment is known to impact growth.
• Significant abnormality in screening laboratory results.
• Have been treated with growth hormone, insulin-like growth factor 1 (IGF 1), or
anabolic steroids in the previous 6 months or long-term treatment (>3 months) at any
time
• Have had regular long-term treatment (>1 month) with oral corticosteroids (low-dose
ongoing inhaled steroid for asthma is acceptable)
• Have had previous guided growth surgery or limb-lengthening surgery within 12 months
prior to screening.
Ribociclib vs. Palbociclib in Patients With Advanced Breast Cancer Within the HER2-Enriched Intrinsic Subtype (HARMONIA)
HARMONIA is an international, multicenter, randomized, open-label and phase III study. The
primary objective of this study is to demonstrate that the combination of ribociclib with
endocrine therapy (letrozole or fulvestrant) is superior to palbociclib with endocrine
therapy (letrozole or fulvestrant) in prolonging progression-free survival in patients with
advanced HR+/HER2- and HER2-E breast cancer. The study will enroll approximately 456 patients
with HER2-E disease from approximately 95 sites worldwide.
In addition, the HARMONIA trial will include an exploratory cohort of patients with HR+/HER2-
and Basal-like disease treated with paclitaxel +/- Tislelizumab. This cohort does not have a
predefined sample size and the objective is only exploratory, given the suggested lack of
efficacy of the combinations of hormone therapy and CDK4/6 inhibitors in this subgroup of
patients. Enrolment into the basal-like cohort will stop once the HER2-E disease cohort is
fully enrolled.
Malinda West, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05207709
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Main
Inclusion Criteria:
• Histologically documented HR-positive and HER2-negative breast cancer by local testing
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• advanced (loco regionally recurrent not amenable to curative therapy or metastatic)
breast cancer.
• Availability of FFPE tumor block for biomarker analysis, obtained during metastatic
period.
• HER2-E or Basal-like subtype as per central PAM50 analysis.
• Measurable disease or non-measurable disease, as defined by RECIST v1.1
• Adequate hematologic and end-organ function
• Patient must be willing and able to comply with scheduled visits, treatment plans,
laboratory tests, and other trial procedures.
• Women of childbearing potential must have confirmed negative serum pregnancy test
within 7 days prior to randomization.
• Women of CBP must be willing to use highly effective methods of contraception.
• Patient must have a 6-lead or 12-lead ECG with ALL of the following parameters at
screening:
• QTcF interval (QT interval using Fridericia's correction) at screening < 450
msec.
• Resting heart rate 50-90 beats per minute (determined from the ECG).
Main
Exclusion Criteria:
• Prior therapy with any CDK4/6 inhibitors.
• Patient has received prior treatment with chemotherapy for advanced/metastatic breast
cancer
Study of DF9001 in Patients With Advanced Solid Tumors
DF9001-001 is a study of a new molecule that targets natural killer (NK) cells and T-cell
activation signals to specific receptors on cancer cells. The study will occur in two phases.
The first phase will be a dose escalation phase, enrolling patients with various types of
solid tumors that express epidermal growth factor receptor (EGFR). A combination therapy
cohort will be opened for enrollment, DF9001 + nivolumab. The second phase will include a
dose expansion using the best dose selected from the first phase of the study. Multiple
cohorts will be opened with eligible patients having selected solid tumors.
Nataliya Uboha, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05597839
Show full eligibility criteria
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Inclusion Criteria:
General (applies to all cohorts)
1. Signed written informed consent.
2. Male or female patients aged ≥ 18 years.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry
and an estimated life expectancy of at least 3 months.
4. Adequate hematological function.
5. Adequate hepatic function.
6. Adequate renal function.
7. Effective contraception for women of child bearing potential (WOCBP) patients as
defined by World Health Organization (WHO) guidelines for 1 "highly effective" method
or 2 "effective" methods.
Inclusion Criteria:
Dose Escalation (Monotherapy and Combination)
1. Histologically or cytologically proven locally advanced or metastatic solid tumors of
epithelial origin with documented EGFR expression on tumor tissue by IHC and must have
progressed on standard of care therapy.
2. Evidence of objective disease, but participation does not require a measurable lesion.
Inclusion Criteria:
Safety PK/PD Expansion Cohorts
1. Histologically or cytologically proven locally advanced or metastatic solid tumor from
the following list, where standard therapy has failed, that has been confirmed to have
EGFR expression via archival or fresh biopsy tissue prior to study enrollment.
i. NSCLC ii. HNSCC iii. CRC iv. Esophageal adenocarcinoma v. Gastric cancer vi. Renal
cell carcinoma vii. Pancreatic cancer
2. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
3. Able and willing to have a fresh tumor biopsy obtained during the screening window and
an on-treatment biopsy for pharmacodynamic analysis.
Inclusion Criteria:
Head and Neck Squamous Cell Carcinoma (HNSCC) Expansion Cohorts
1. Histologically or cytologically documented relapsed or metastatic HNSCC that has been
confirmed to have EGFR expression via archival or fresh biopsy tissue prior to study
enrollment. Primary tumor locations include oropharynx, oral cavity, hypopharynx, or
larynx. Participants may not have a primary tumor site of nasopharynx (any histology).
2. Participants must have radiographic disease progression while on or after having
received both platinum-based chemotherapy and an anti-PD-(L)1 antibody, administered
either concurrent or sequentially.
3. Documented EGFR expression by IHC.
4. Able and willing to have a fresh tumor biopsy obtained during the screening window and
an on-treatment biopsy for pharmacodynamic analysis.
Inclusion Criteria:
Colorectal Cancer (CRC) Expansion Cohorts
1. Histologically or cytologically documented relapsed or metastatic colorectal cancer
that has been confirmed to have EGFR expression via archival or fresh biopsy tissue
prior to study enrollment.
2. Must have received 1 line of either FOLFOX, CAPOX, FOLFIRI, or FOLFOXIRI with or
without a biological agent. Prior treatment with an anti-EGFR antibody is required for
RAS wild-type participants.
3. Participants cannot be known mismatch repair (MMR)/MSI high.
4. Participants must not have received an anti-PD-(L)1.
5. Participants must have radiographic disease progression while or after receiving
treatment for their advanced (recurrent/unresectable/metastatic) disease.
6. Presence of at least 1 tumor lesion accessible for biopsy. A fresh tumor biopsy must
be obtained and shipped for analysis at the Sponsor-designated laboratory during the
screening window and while on study treatment in accordance with the study Laboratory
Manual.
Inclusion Criteria:
Non-Small Cell Lung Cancer (NSCLC) Expansion Cohorts
1. Histologically confirmed NSCLC meeting stage criteria for stage IIIB, stage IV (per
the 7th IASCLC classification of NSCLC), or recurrent disease that has been confirmed
to have EGFR expression via archival or fresh biopsy tissue prior to study enrollment.
2. Patients must have recurrent or progressive disease during or after first line
combination therapy with checkpoint inhibitors and platinum-based chemotherapy. They
must not have received any subsequent lines of therapy.
3. Patients with Stage IIIB must be ineligible for local therapies with curative intent
(eg, radiotherapy or surgery).
4. Patients must have received and progressed on or after anti-PD-(L)1 therapy including
those with actionable genomic alterations.
5. Status for actionable mutations (EGFR, ALK, ROS1, RET, etc.) must be known (when
testing is available as per country/region standard of care practices); patients with
actionable mutations must have received and progressed on, have been intolerant to, or
not be a candidate for standard TKIs (as available per country/region standard of care
practices).
6. Presence of at least 1 tumor lesion accessible for biopsy. A fresh tumor biopsy must
be obtained and shipped for analysis at the Sponsor-designated laboratory during the
screening window and while on study treatment in accordance with the study Laboratory
Manual.
Exclusion Criteria:
1. Participants must not have had chemotherapy, radiotherapy (other than palliative
bone-directed radiotherapy), or major surgery, or received another investigational
agent within 28 days or 5-half-lives of the drug (if known), whichever is shorter,
before the start of study treatment.
2. Concurrent anticancer treatment (eg, cytoreductive therapy, radiotherapy [except for
palliative bone-directed radiotherapy], immune therapy, or cytokine therapy [except
for erythropoietin]), major surgery (excluding prior diagnostic biopsy), concurrent
systemic therapy with steroids or other immunosuppressive agents, or use of any
investigational drug within 28 days or 5-half-lives of the drug (if known), whichever
is shorter, before the start of study treatment. Short-term administration of systemic
steroids (eg, for allergic reactions or the management of irAEs) is allowed.
Note: Participants receiving bisphosphonate or denosumab are eligible, provided
treatment was initiated at least 14 days before the first dose of DF9001.
3. Previous malignant disease other than the target malignancy to be investigated in this
study within the last 3 years, with the exception of basal or squamous cell carcinoma
of the skin, low-grade prostate cancer (Gleason score of ≤6), or cervical carcinoma in
situ.
4. Life expectancy of less than 3 months.
5. Participants with brain metastases are excluded, unless all of the following criteria
are met:
• Central nervous system (CNS) lesions are asymptomatic, previously treated and no
active therapy is required (i.e., no steroids for edema).
• Imaging demonstrates stability of disease 28 days from last treatment for CNS
metastases.
6. Receipt of any organ transplantation, including autologous or allogeneic stem-cell
transplantation.
7. Significant acute or chronic infections (including historic positive test for human
immunodeficiency virus [HIV], or active or latent hepatitis B or active hepatitis C
tested during the screening window). If HBsAg is negative and the anti-hepatitis B
core antibody is positive, then hepatitis B viral DNA load must be undetectable.
8. Preexisting autoimmune disease (except for participants with vitiligo) needing
treatment with systemic immunosuppressive agents for more than 28 days within the last
3 years, or clinically relevant immunodeficiencies (eg, dysgammaglobulinemia or
congenital immunodeficiencies). Participants with a history of immune related
endocrinopathies (e.g. hypothyroidism, type 1 diabetes mellitus [TIDM] and adrenal
insufficiency) that are stable on hormone replacement therapy may be eligible for this
study.
9. Participants with a known medical history that may place them at risk of known
toxicities of EGFR-blockage.
• History of or ongoing keratitis, ulcerative keratitis, or corneal perforation,
• History of cardiopulmonary arrest unless this was caused by an acute, reversible
etiology that is no longer present.
• History of or ongoing pulmonary fibrosis or interstitial lung disease.
10. Known severe hypersensitivity reactions to monoclonal antibodies (≥Grade 3 of the
NCI-CTCAE v5.0), any history of anaphylaxis, or uncontrolled asthma (ie, 3 or more
features of partly controlled asthma).
11. Persisting toxicity related to prior therapy >Grade 1 NCI-CTCAE v5.0; however,
alopecia ≤Grade 2, endocrinopathies ≤Grade 2, and sensory neuropathy ≤Grade 2 is
acceptable.
12. Participants who have received an anti-PD-(L)1 as a previous line of therapy are
eligible for the study, unless they have experienced either:
• a Grade 3 or 4 drug-related toxicity during and attributed to treatment with the
anti-PD-(L)1.
• a Grade 2 drug-related toxicity that impacted either the lungs or the nervous
system, caused by the administration of the anti-PD-(L)1.
13. Pregnancy or lactation in females during the study.
14. Known alcohol or drug abuse.
15. Serious cardiac illness or medical conditions, including but not limited to:
• History of New York Heart Association class III or IV heart failure or systolic
dysfunction (left ventricular ejection fraction [LVEF] <55%).
• High-risk uncontrolled arrhythmias (eg, tachycardia with a heart rate >100/min at
rest).
• Significant ventricular arrhythmia (ventricular tachycardia) or higher-grade
atrioventricular (AV) block (eg, AV-block, second degree AV block Type 2 [Mobitz
2], or third-degree AV-block).
• Angina pectoris requiring anti-anginal medication.
• Clinically significant valvular heart disease.
• Evidence of transmural infarction on ECGs.
• Poorly controlled hypertension (defined as systolic >160 mm Hg or diastolic >100
mm Hg).
• Clinically relevant uncontrolled cardiac risk factors, clinically relevant
pulmonary disease, or any clinically relevant medical condition in the opinion of
the Investigator that may limit participation in this study.
• Severe dyspnea at rest due to complications of advanced malignancy or requiring
supplementary oxygen therapy.
16. All other significant diseases (eg, inflammatory bowel disease), which, in the opinion
of the Investigator, might impair the participant's ability to participate.
17. Any psychiatric condition that would prohibit the understanding or rendering of
informed consent.
18. Legal incapacity or limited legal capacity.
19. Incapable of giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the ICF and in this protocol.
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, Solid Tumor, Adult
Standardizing Treatments for Pulmonary Exacerbations - Aminoglycoside Study (STOP360AG)
The purpose of this study is to look at pulmonary exacerbations in people with cystic
fibrosis (CF) that need to be treated with antibiotics given through a tube inserted into a
vein (intravenous or IV). A pulmonary exacerbation is a worsening of respiratory symptoms in
people with CF that needs medical intervention. Both doctors and CF patients are trying to
understand the best way to treat pulmonary exacerbations. This study is trying to answer the
following questions about treating a pulmonary exacerbation:
- Do participants have the same improvement in lung function and symptoms if they are
treated with one type of antibiotic (called beta-lactams or β-lactams) versus taking two
different types of antibiotics (tobramycin and β-lactams)?
- Is taking one type of antibiotic just as good as taking two types?
Andrew Braun
All
6 Years and over
Phase 4
This study is NOT accepting healthy volunteers
NCT05548283
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Inclusion Criteria:
• All genders ≥ 6 years of age at Visit 1
• Documentation of a CF diagnosis
• Clinician intent to treat index CF PEx with a planned 14-day course of IV
antimicrobials
• At least one documented Pa positive culture within two years prior to Visit 1
Exclusion Criteria:
• Participant is not pregnant
• No known renal impairment or history of solid organ transplantation
• No IV antimicrobial treatment, ICU admission, pneumothorax, or hemoptysis within 6
weeks prior to Visit 1
• No use of investigational therapies, new CF transmembrane conductance regulator (CFTR)
modulators, or treatment for Nontuberculous mycobacteria (NTM) within 4 weeks prior to
Visit 1
• No history of hypersensitivity, vestibular, or auditory toxicity with aminoglycosides
• No more than one day of IV aminoglycosides administered for the current PEx treatment
prior to Visit 1
Cystic Fibrosis, Cystic Fibrosis Pulmonary Exacerbation, Other
Testing Radiation and HER2-targeted Therapy Versus HER2-targeted Therapy Alone for Low-risk HER2-positive Breast Cancer (HERO)
This Phase III trial compares the recurrence-free interval (RFI) among patients with
early-stage, low risk HER2+ breast cancer who undergo breast conserving surgery and receive
HER2-directed therapy, and are randomized to not receive adjuvant breast radiotherapy versus
those who are randomized to receive adjuvant radiotherapy per the standard of care.
Bethany Anderson, MD
All
40 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05705401
Show full eligibility criteria
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Inclusion Criteria:
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry and, for patients treated in the U.S.,
authorization permitting release of personal health information.
• female and male patients who have undergone breast conserving surgery and completed a
minimum of 4 cycles (12 weeks) of neoadjuvant or adjuvant chemotherapy in combination
with HER2-targeted therapy.
-≥ 40 years of age
• ECOG performance status of 0 ,1, or 2/Karnofsky performance status above 60
• Histologically or cytologically confirmed invasive breast carcinoma.
• tumor must have been determined to be HER2-positive by current ASCO/CAP guidelines
based on local testing results.
• Patient must have undergone axillary staging, either sentinel node biopsy (SNB) or
axillary lymph nodal dissection (ALND). In neoadjuvant patients, SNB following
neoadjuvant therapy is strongly recommended. SNB prior to neoadjuvant therapy is
discouraged, but patients are permitted if node negative (pN0).
• The following staging criteria must be met according to AJCC 8th edition criteria:
Adjuvant cohort : By pathologic evaluation, the patient's primary tumor must be = 2 cm
and ipsilateral nodes must be pN0. Surgical lumpectomy margins must be negative for
invasive cancer and ductal carcinoma in situ (no ink on tumor).
Neoadjuvant cohort: Prior to neoadjuvant therapy, the patient's primary tumor must be < 3
cm by imaging studies, with negative axillary nodes (cN0) based on axillary U/S, CT, PET or
MRI. Physical examination is not sufficient documentation of cN0 status; • Must be ypT0N0
at surgery (lumpectomy); patients with residual non-invasive disease (DCIS) in the surgical
specimen (ypTis), are NOT eligible.
• For the Adjuvant cohort, adjuvant therapy must have consisted of a minimum of 4 cycles
(12 weeks) of chemotherapy in combination with HER2-targeted therapy.
• For the Neoadjuvant cohort, neoadjuvant therapy must have consisted of a minimum of 4
cycles (12 weeks) of chemotherapy in combination with HER2-targeted therapy.- ;
Patients who did not receive chemotherapy in the neoadjuvant setting are not eligible,
even if they achieved pCR with their preoperative treatment; nor would these patients
become eligible by receiving chemotherapy after surgery.
• In patients assigned to radiation therapy, treatment should start ≤ 12 weeks from
surgery on the Neoadjuvant cohort and ≤ 8 weeks from the completion of chemotherapy on
the Adjuvant cohort. Patients should continue HER2-targeted therapy during assigned
study treatment (radiation or observation).
• Bilateral mammogram or MRI within 52 weeks prior to randomization.
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral
load within 6 months of randomization are eligible for this trial.
Exclusion Criteria:
• Definitive clinical or radiologic evidence of metastatic disease.
• On the Adjuvant cohort, patients with a primary tumor >2 cm on pathologic examination
of the surgical specimen. On the Neoadjuvant cohort, patients with a primary tumor > 3
cm or with abnormal or suspicious ipsilateral axillary nodes by pretreatment imaging,
unless demonstrated to be negative by cytologic or histologic examination.
• Pathologically positive axillary nodes at any time including of pN0(i+) or pN0(mol+)
ypN0(i+) or ypN0(mol+) disease.
• Patient planning for or status-post mastectomy.
• Radiographically suspicious ipsilateral or contralateral axillary, supraclavicular,
infraclavicular, or internal mammary lymph nodes, unless there is histological
confirmation that these nodes are negative for metastatic disease.
• Suspicious microcalcifications, densities, or palpable abnormalities (in the
ipsilateral or contralateral breast), or mass or non-mass enhancement on MRI (if
performed) aside from the known cancer, unless biopsied and found to be benign.
• Non-epithelial breast malignancies such as sarcoma or lymphoma.
• Multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant or
separated by > 4 centimeters. If multifocal, all foci should be confined to a maximum
tumor bed of 3 cm determined by pathological assessment.
• Paget's disease of the nipple.
• Synchronous (unilateral or bilateral) invasive breast cancer or DCIS. (Patients with
synchronous and/or previous contralateral LCIS are eligible.)
• On the Adjuvant cohort, surgical margins that cannot be microscopically assessed or
are positive at pathologic evaluation. (If surgical margins are rendered free of
disease by re-excision, the patient is eligible).
• Treatment plan that includes regional nodal irradiation.
• Patients treated for a prior invasive breast malignancy are excluded. Contralateral
DCIS ≥ 10 years prior to enrollment is permissible.
• 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 on oral, transdermal, or subdermal estrogen replacement (including all
estrogen only and estrogen-progesterone formulas) are not eligible unless discontinued
prior to randomization.
• Prior ipsilateral breast or thoracic RT for any condition (contralateral RT for DCIS ≥
10 years prior to randomization is permitted).
• Active collagen vascular disease, specifically dermatomyositis with a CPK level above
normal or with an active systemic lupus erythematosus, or scleroderma.
• Clinicians should consider whether any conditions would make this protocol
unreasonably hazardous for the patient.
• Pregnancy or lactation at the time of randomization or intention to become pregnant
during treatment. (Note: Pregnancy testing according to institutional standards for
patients of childbearing potential must be performed within 14 days prior to
randomization.)
• Use of any investigational product within 30 days prior to randomization.
Selinexor in Maintenance Therapy After Systemic Therapy for Participants With p53 Wild-Type, Advanced or Recurrent Endometrial Carcinoma (XPORT-EC-042)
The purpose of this study is to evaluate the efficacy and safety of selinexor as a
maintenance treatment in patients with p53 wt endometrial carcinoma (EC), who have achieved a
partial response (PR) or complete response (CR) (per Response Evaluation Criteria in Solid
Tumors version 1.1 [RECIST v 1.1]) after completing at least 12 weeks of platinum-based
therapy. A total of 220 participants will be enrolled in the study and randomized in a 1:1
ratio to maintenance therapy with either selinexor or placebo.
Ellen Hartenbach, M.D.
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05611931
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Inclusion Criteria:
• At least 18 years of age at the time of signing informed consent.
• Histologically confirmed EC including: endometrioid, serous, undifferentiated, and
carcinosarcoma.
• TP53 wt assessed by next generation sequencing (NGS), evaluated by a central vendor.
• Completed a single line, at least 12 weeks of platinum-based therapy (not including
adjuvant or neoadjuvant therapy for Stage I-III disease) and achieved confirmed
partial or complete response (PR or CR) by imaging, according to RECIST version 1.1.
The participants should have received treatment for:
Primary Stage IV disease, defined as:
• had a primary or later debulking surgery during first-line platinum-based therapy with
R0 resection (R0 resection indicates a macroscopic complete resection of all visible
tumor) and achieved CR after at least 12 weeks platinum-based therapy, OR
• had a primary or later debulking surgery during first-line platinum-based therapy with
R1 resection (R1 resection indicates incomplete removal of all macroscopic disease)
and achieved PR or CR after at least 12 weeks platinum-based chemotherapy, OR
• had no surgery and achieved PR or CR after at least 12 weeks platinum-based
chemotherapy
OR
At first relapse (i.e., relapse after primary therapy including surgery and/or chemotherapy
and/or immunotherapy for Stage I-IV disease), defined as:
• had Stage I •III disease at diagnosis and received, at initial diagnosis, adjuvant
chemotherapy and relapsed later. Participants should have PR or CR after at least 12
weeks of platinum-based chemotherapy compared with the start of this chemotherapy at
the time of relapse,
• had Stage I-III disease at diagnosis and did not receive adjuvant chemotherapy at
initial diagnosis and relapsed later. Participants should have PR or CR after at least
12 weeks of platinum-based chemotherapy compared with the start of this chemotherapy
at the time of relapse, OR
• had Stage IV disease at diagnosis and received initially chemotherapy with or without
surgery and relapsed later. At the time of relapse, participants should have PR or CR
after at least 12 weeks of platinum-based chemotherapy compared with the start of this
chemotherapy at the time of relapse.
• Previous treatment with anti-programmed cell death protein 1(PD-1) or
anti-programmed death-ligand 1(PD-L1) monoclonal antibody and concomitant
biologic agents (e.g., bevacizumab, trastuzumab) is allowed.
• Must be able to initiate study drug 3 to 8 weeks after completion of their final
dose of chemotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Participants must have adequate bone marrow function and organ function within 2
weeks before starting study drug as defined by the following laboratory criteria:
• Hepatic function: total bilirubin up to less than (<) 3*upper limit of normal (ULN);
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal
to (<=) 2.5*ULN in participants without liver metastasis. For participants with known
liver involvement of their tumor: AST and ALT (<=) 5*ULN
• Hematopoietic function within 1 week: Absolute neutrophil count (ANC) greater than or
equal to (>=) 1.5*10^9/liter (L); platelet count >= 100*10^9/L; hemoglobin >= 9.0 gram
per deciliter (g/dL) per local laboratory results
• Renal function: estimated creatinine clearance (CrCl) of >= 20 milliliter per minute
(mL/min), calculated using the standard local formula, as applicable
•In the opinion of the Investigator, the participant must:
• Have a life expectancy of at least 12 weeks, and
• Be fit to receive investigational therapy
• Premenopausal females of childbearing potential must have a negative pregnancy
test (serum β-human chorionic gonadotropin test) prior to the first dose of study
drug. Female participants of childbearing potential must agree to use highly
effective methods of contraception throughout the study and for 90 days following
the last dose of study drug.
• Written informed consent signed in accordance with federal, local, and
institutional guidelines prior to the first screening procedure.
Exclusion Criteria:
• Participants meeting any of the following exclusion criteria are not eligible to
enroll in this study:
• Has any uterine sarcomas (carcinosarcomas •not excluded), clear cell or small cell
carcinoma with neuroendocrine differentiation
• Received a blood or platelet transfusion during the 2 weeks prior to Cycle 1 Day 1
(C1D1). Participants' hemoglobin must be assessed within 2 weeks of screening and at
least 1 week post transfusion
• Concurrent systemic steroid therapy higher than physiologic dose (> 10 milligram per
day [mg/day] of prednisone or equivalent). Systemic steroid therapy as pre-medication
for taxane is allowed
• Insufficient time since or not recovered from procedures or anti-cancer therapy,
defined as:
• Not recovered from major surgery <= 28 days prior to Day 1 dosing. Minor
procedures, such as biopsies, dental work, or placement of a port or intravenous
(IV) line for infusion are permitted
• Having ongoing clinically significant anti-cancer therapy-related toxicities CTCAE
Grade > 1, with the exception of alopecia. In specific cases, participants whose
toxicity has stabilized or with Grade 2 non-hematologic toxicities can be allowed
following documented approval by the Sponsor's Medical Monitor
• Palliative radiotherapy within 14 days of the intended C1D1. Palliative radiotherapy
may be permitted for symptomatic control of pain from bone metastases, provided that
the radiotherapy does not involve target lesions, and the reason for the radiotherapy
does not reflect evidence of disease progression.
• Any gastrointestinal dysfunctions that could interfere with the absorption of
selinexor (e.g., bowel obstruction, inability to swallow tablets, malabsorption
syndrome, unresolved nausea, vomiting, diarrhea CTCAE v 5.0 > grade 1).
• Participants unable to tolerate two forms of antiemetics for at least 2 cycles will
not be eligible for the trial.
• Active, ongoing or uncontrolled active infection requiring parenteral antibiotics,
antivirals, or antifungals within 1 week of screening.
• Serious psychiatric or medical condition that could interfere with participation in
the study or in the opinion of the Investigator would make study involvement
unreasonably hazardous.
• Previous treatment with an XPO1 inhibitor.
• Stable disease or PD on the post-chemotherapy scan or clinical evidence of progression
prior to randomization.
• Participants who received any systemic anticancer therapy including investigational
agents <= 3 weeks (or <= 5 half-lives of the drug [whichever is shorter]) prior to
C1D1.
• Major injuries or surgery within 14 days prior to C1D1 and/or planned major surgery
during the on-treatment study period.
• Other malignant disease with disease-free <= 3 years except: curatively treated
carcinoma in situ of the cervix, basal cell carcinoma of the skin, or ductal carcinoma
in situ (DCIS) of the breast.
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to selinexor, or other agents used in the study.
• Active brain metastases (e.g., stable for < 8 weeks, no adequate previous treatment
with radiotherapy and/or surgery, symptomatic, requiring treatment with
anti-convulsant therapy. Corticoid therapy is allowed if administered as stable dose
for at least 1 month before randomization).
• Females who are pregnant or lactating.
• Any other life-threatening illness, active medical condition, organ system
dysfunction, or serious active psychiatric issue which, in the Investigator's opinion,
could compromise the participant's safety or the participant's ability to remain
compliant with study procedures.
A Trial Comparing Unrelated Donor BMT With IST for Pediatric and Young Adult Patients With Severe Aplastic Anemia (TransIT, BMT CTN 2202) (TransIT)
Severe Aplastic Anemia (SAA) is a rare condition in which the body stops producing enough new
blood cells. SAA can be cured with immune suppressive therapy or a bone marrow transplant.
Regular treatment for patients with aplastic anemia who have a matched sibling (brother or
sister), or family donor is a bone marrow transplant. Patients without a matched family donor
normally are treated with immune suppressive therapy (IST). Match unrelated donor (URD) bone
marrow transplant (BMT) is used as a secondary treatment in patients who did not get better
with IST, had their disease come back, or a new worse disease replaced it (like leukemia).
This trial will compare time from randomization to failure of treatment or death from any
cause of IST versus URD BMT when used as initial therapy to treat SAA.
The trial will also assess whether health-related quality of life and early markers of
fertility differ between those randomized to URD BMT or IST, as well as assess the presence
of marrow failure-related genes and presence of gene mutations associated with MDS or
leukemia and the change in gene signatures after treatment in both study arms.
This study treatment does not include any investigational drugs. The medicines and procedures
in this study are standard for treatment of SAA.
Kenneth Desantes, M.D.
All
0 Years to 25 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT05600426
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Inclusion Criteria:
To be eligible to participate in the randomized trial, an individual must meet all the
following criteria:
1. Provision of signed and dated informed consent form for the randomized trial by
patient and/or legal guardian.
2. Age ≤25 years old at time of randomized trial consent.
3. Confirmed diagnosis of idiopathic SAA, defined as:
1. Bone marrow cellularity <25%, or <30% hematopoietic cells.
2. Two of three of the following (in peripheral blood): neutrophils <0.5 x 10^9/L,
platelets <20 x 10^9/L, absolute reticulocyte count <60 x 10^9/L or hemoglobin <8
g/dL.
4. No suitable fully matched related donor available (minimum 6/6 match for HLA-A and B
at intermediate or high resolution and DRB1 at high resolution using DNA based
typing).
5. At least 2 unrelated donors noted on NMDP search who are well matched (9/10 or 10/10
for HLA-A, B, C, DRB1, and DQB1 using high resolution).
6. In the treating physician's opinion, no obvious contraindications precluding them from
BMT or IST.
Exclusion Criteria:
1. Presence of Inherited bone marrow failure syndromes (IBMFS). The diagnosis of Fanconi
anemia must be excluded by diepoxybutane (DEB) or equivalent testing on peripheral
blood or marrow. Telomere length testing should be sent on all patients to exclude
Dyskeratosis Congenita (DC), but if results are delayed or unavailable and there are
no clinical manifestations of DC, patients may enroll. If patients have clinical
characteristics suspicious for Shwachman-Diamond syndrome, this disorder should be
excluded by pancreatic isoamylase testing or gene mutation analysis (note: pancreatic
isoamylase testing is not useful in children <3). Other testing per center may be
performed to exclude IBMFS.
2. Clonal cytogenetic abnormalities or Fluorescence In-Situ Hybridization (FISH) pattern
consistent with pre- myelodysplastic syndrome (pre-MDS) or MDS on marrow examination.
3. Known severe allergy to ATG.
4. Prior allogeneic or autologous stem cell transplant.
5. Prior solid organ transplant.
6. Infection with human immunodeficiency virus (HIV).
7. Active Hepatitis B or C. This only needs to be excluded in patients where there is
clinical suspicion of hepatitis (e.g., elevated LFTs).
8. Female patients who are pregnant or breast-feeding.
9. Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma
in situ.
10. Disease modifying treatment prior to study enrollment, including but not limited to
use of androgens, eltrombopag, romiplostim, or immune suppression. Note: Supportive
care measures such as G-CSF, blood transfusion support and antibiotics are allowable
Severe Aplastic Anemia, Other Hematopoietic, Hematologic cancers, other
Testing the Addition of Stereotactic Radiation Therapy With Immune Therapy for the Treatment of Patients With Unresectable or Metastatic Renal Cell Cancer, SAMURAI Study (SAMURAI)
This phase II trial tests whether the addition of radiation to the primary tumor, typically
given with stereotactic ablative radiation therapy (SABR), in combination with standard of
care immunotherapy improves outcomes in patients with renal cell cancer that is not
recommended for surgery and has spread to other places in the body (metastatic). Radiation
therapy uses high energy photons to kill tumor cells and shrink tumors. Stereotactic body
radiation therapy uses special equipment to position a patient and deliver radiation to
tumors with high precision. This method may kill tumor cells with fewer doses of radiation
over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal
antibodies, such as nivolumab, ipilimumab, avelumab, and pembrolizumab, may help the body's
immune system attack the cancer, and may interfere with the ability of tumor cells to grow
and spread. Axitinib, cabozantinib, and lenvatinib are in a class of medications called
antiangiogenic agents. They work by stopping the formation of blood vessels that bring oxygen
and nutrients to tumor. This may slow the growth and spread of tumor. Giving SABR in
combination with standard of care immunotherapy may help shrink or stabilize the cancer in
patients with renal cell cancer.
Hamid Emamekhoo, M.D.
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05327686
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Inclusion Criteria:
• Pathologically (histologically or cytologically) proven diagnosis of renal cell
carcinoma prior to registration
• Node-positive unresectable (TxN1Mx) or metastatic (TxNxM1) based on the following
diagnostic workup:
• History/physical examination within 45 days prior to registration
• CT/magnetic resonance imaging (MRI) of the chest/abdomen/pelvis within 45 days
prior to registration
• Patients must have IMDC intermediate (1-2 factors) or poor risk disease (>= 3 factors)
• 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 measurable disease (node positive or metastatic) as defined by RECIST
version 1.1 excluding the primary renal tumor
• Patient not recommended for or refused immediate cytoreductive nephrectomy
• Candidate for standard of care therapy with either immuno-oncology (IO)-IO or IO-VEGF
combination regimen
• Primary renal tumor measuring 20 cm or less in anterior to posterior dimension only on
axial imaging
• Age >= 18
• Karnofsky performance status >= 60 within 45 days prior to registration
• Hemoglobin >= 8 g/dL (transfusions are allowed) (within 45 days prior to registration)
• Platelet count >= 50,000/mm^3 (within 45 days prior to registration)
• Absolute neutrophil count (ANC) >= 1500/mm^3 (within 45 days prior to registration)
• Calculated (Calc.) creatinine clearance >= 30 mL/min (within 45 days prior to
registration)
• For African American patients specifically whose renal function is not considered
adequate by the formula above, an alternative formula that takes race into
account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula)
should be used for calculating the related estimated glomerular filtration rate
(GFR) with a correction factor for African American race creatinine clearance for
trial eligibility, where GFR >= 30 mL/min/1.73m^2 will be considered adequate
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert
Syndrome, who can have total bilirubin < 3.0 mg/dL) (within 45 days prior to
registration)
• Aspartate aminotransferase and alanine aminotransferase (AST and ALT) =< 3 x upper
limit of normal (ULN) or < 5 x ULN if hepatic metastases present (within 45 days prior
to registration)
• Patients with known human immunodeficiency virus (HIV) on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial.
Testing is not required for entry into protocol
• 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. Patients with HCV infection who are currently on treatment are eligible if
they have an undetectable HCV viral load
• The patient must agree to use a highly effective contraception, including men with
vasectomies if they are having sex with a woman of childbearing potential or with a
woman who is pregnant, while on study drug and for 6 months following the last dose of
study drug. 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
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry and, for patients treated in the United States
(U.S.), authorization permitting release of personal health information
Exclusion Criteria:
• Patients with planned treatment of all metastatic disease with definitive therapy
including either surgery, ablative (non-palliative) doses of radiation, or
intervention of some type (definitive interventional radiology techniques) to ALL
metastatic sites rendering the patient without extra-renal measurable disease.
Patients NOT planned for definitive treatment of all metastatic sites are eligible.
Lesions radiated palliatively are not eligible for response assessment
• Patients with untreated or unstable brain metastases or cranial epidural disease
• Note: Patients who have been adequately treated with radiotherapy, radiosurgery,
or surgery and stable for at least 4 weeks prior to registration as documented by
MRI or CT imaging or deemed stable by clinical investigator are eligible. Treated
brain metastases are defined as having no ongoing requirement for steroids and no
evidence of progression or hemorrhage after treatment for at least 4 weeks prior
to registration as documented by MRI or CT imaging or deemed stable by clinical
investigator
• Prior radiotherapy to the kidney that would result in overlap of radiation therapy
fields treatment of the primary tumor
• Any systemic therapy for metastatic renal cell carcinoma (RCC) that was initiated > 90
days before registration, note that prior chemotherapy for a different cancer is
allowed (completed > 3 years prior to registration)
• Severe, active comorbidity defined as follows:
• Active autoimmune disease requiring ongoing therapy including systemic treatment
with corticosteroids (> 10 mg daily prednisone equivalents) or other
immunosuppressive medications daily. Inhaled steroids and adrenal replacement
steroid doses > 10 mg daily prednisone equivalents are permitted in the absence
of active autoimmune disease
• History of severe allergic, anaphylactic or other hypersensitivity reactions to
chimeric or humanized antibodies
• Active tuberculosis (purified protein derivative [PPD] response without active
tuberculosis [TB] is allowed)
• Uncontrolled hypertension (systolic blood pressure [BP] > 190 mmHg or diastolic
BP > 110 mmHg)
• Major surgery requiring hospital admission ≤ 28 days prior to registration.
• Any serious (requiring hospital stay or long-term rehab) non-healing wound,
ulcer, or bone fracture within 45 days prior to registration
• Any arterial thrombotic (ST elevation myocardial infarction [STEMI], non-ST
elevation myocardial infarction [NSTEMI], cerebrovascular accident [CVA], etc)
events within 180 days prior to registration
• Active New York (NY) Heart Association class 3-4 heart failure symptoms
• Moderate or severe hepatic impairment (Child-Pugh B or C)
• Any history of untreated pulmonary embolism or deep venous thrombosis (DVT)
within 180 days prior to registration. (Any asymptomatic or treated pulmonary
embolism or asymptomatic treated deep venous thrombosis > 30 days prior to
registration is allowed)
• Unstable cardiac arrhythmia within 180 days prior to registration
• History of abdominal fistula, gastrointestinal perforation, intra-abdominal
abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior
to registration
• History of or active inflammatory bowel disease
• Malabsorption syndrome within 45 days prior to registration
• Pregnancy and individuals unwilling to discontinue nursing. For women of child bearing
potential must have a negative pregnancy test =< 45 days prior to registration
Metastatic Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Unresectable Renal Cell Carcinoma, Kidney
Testing the Addition of Duvelisib or CC-486 to the Usual Treatment for Peripheral T-Cell Lymphoma
This phase II trial studies the effect of duvelisib or CC-486 and usual chemotherapy
consisting of cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone in
treating patients with peripheral T-cell lymphoma. Duvelisib may stop the growth of cancer
cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as
CC-486, cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone, work in
different ways to stop the growth of cancer cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. This trial may help find out if this
approach is better or worse than the usual approach for treating peripheral T-cell lymphoma.
Saurabh Rajguru, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04803201
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Inclusion Criteria:
• Histologically confirmed diagnosis of peripheral T-cell lymphoma (PTCL) with < 10%
CD30 expression by immunohistochemistry in the following subtypes (by local review):
nodal T-cell lymphoma with T-follicular helper (TFH) phenotype (TFH-PTCL), follicular
T-cell lymphoma, PTCL-not otherwise specified (NOS), angioimmunoblastic T-cell
lymphoma (AITL), enteropathy associated T-cell lymphoma, monomorphic epitheliotropic
intestinal T-cell lymphoma
• Patients with expression of CD30 in >= 10% of the tumor (based on local
immunohistochemistry review) regardless of histology will not be permitted
• Patients with a diagnosis of other PTCL subtype histologies other than those
specified in the inclusion criteria are excluded including large cell
transformation of mycosis fungoides
• Patients will be stratified by presence or absence of TFH phenotype (i.e.
diagnosis of AITL, TFH-PTCL, follicular T-cell lymphoma) based on local review of
pathology. Determination of TFH phenotype can be defined by expression of two or
more of the following markers CD10, BCL6, CXCL13, ICOS, and PD1 by
immunohistochemistry
• Measurable disease as defined by the Lugano criteria
• No prior systemic therapy for lymphoma (excluding corticosteroids)
• Not pregnant and not nursing, because this study involves an investigational agent
whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn
are unknown. Therefore, for women of childbearing potential only, a negative urine or
serum pregnancy test done =< 7 days prior to registration is required
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Platelet count >= 75,000/mm^3 (>= 50,000/mm^3 if secondary to bone marrow involvement
from lymphoma per investigator assessment; the first 12 patients on each arm of the
study must have platelets >= 75,000/mm^3 regardless of bone marrow involvement)
• Absolute neutrophil count (ANC) >= 1,000/mm^3
• Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or
alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 3.0 x
upper limit of normal (ULN)
* Except in subjects with documented liver involvement by lymphoma
• Calculated creatinine clearance >= 30 mL/min by Cockcroft-Gault formula
• Total bilirubin =< 2.0 x ULN
* Except in cases of Gilbert's Syndrome or documented liver or pancreatic involvement
by lymphoma
• Archival tissue must be available for submission
• Patients known to have HTLV 1/2 are excluded
• Patients with known central nervous system involvement are excluded
• No active viral infection with human immunodeficiency virus (HIV), hepatitis B, or
hepatitis C. Those who are seropositive (e.g. hepatitis B core antibody [Ab] positive)
are permitted if they are negative by polymerase chain reaction (PCR). Those who are
seropositive for hepatitis B and are negative for hepatitis B virus (HBV)
deoxyribonucleic acid (DNA) by PCR must receive concomitant hepatitis B directed
antiviral therapy. Those who have hepatitis C Ab positivity who have completed
curative therapy for hepatitis C with negative hepatitis C PCR are eligible
• Patients with history of HIV are eligible if they have an undetectable viral load for
at least 6 months
• No active uncontrolled systemic fungal, bacterial or viral infection (defined as
ongoing signs/symptoms related to the infection without improvement despite
appropriate antibiotics, antiviral therapy and/or other treatment). Patients with
Epstein-Barr virus (EBV) viremia related to their lymphoma are permitted
• No concurrent malignancy requiring active therapy within the last 3 years with the
exception of basal cell carcinoma limited to the skin, squamous cell carcinoma limited
to the skin, carcinoma in situ of the cervix, breast or localized prostate cancer.
Adjuvant hormonal therapy for cancer previously treated for curative intent is
permitted
• Patients must have documented left ventricular ejection fraction of >= 45%
• No significant active cardiac disease within the previous 6 months including:
• New York Heart Association (NYHA) class III or IV congestive heart failure
• Unstable angina or angina requiring surgical or medical intervention; and/or
• Myocardial infarction
• No contraindication to any drug in the chemotherapy regimen, including neuropathy >=
grade 2
• Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this
study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days
prior to registration on the study. Chronic concomitant treatment with strong CYP3A4
inducers is not allowed. Patients must discontinue the drug 14 days prior to the start
of study treatment
Testing the Addition of Whole Brain Radiotherapy Using a Technique That Avoids the Hippocampus to Stereotactic Radiosurgery in People With Cancer That Has Spread to the Brain and Come Back in Other Areas of the Brain After Earlier Stereotactic Radiosurgery
This phase III trial compares the effect of adding whole brain radiotherapy with hippocampal
avoidance and memantine to stereotactic radiosurgery versus stereotactic radiosurgery alone
in treating patients with cancer that has spread to the brain and come back in other areas of
the brain after earlier stereotactic radiosurgery. Hippocampus avoidance during whole-brain
radiation therapy decreases the amount of radiation that is delivered to the hippocampus,
which is a brain structure that is important for memory. The medicine memantine is also often
given with whole brain radiation therapy because it may decrease the risk of side effects of
radiation on thinking and memory. Stereotactic radiosurgery delivers a high dose of radiation
only to the small areas of cancer in the brain and avoids the surrounding normal brain
tissue. Adding whole brain radiotherapy with hippocampal avoidance and memantine to
stereotactic radiosurgery may be effective in shrinking or stabilizing cancer that has spread
to the brain and returned in other areas of the brain after receiving stereotactic
radiosurgery.
Andrew Baschnagel, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04588246
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Inclusion Criteria:
• Patients must have developed their first or second distant brain relapse(s) at least 8
weeks after upfront SRS and within 21 days prior to randomization
• Distant brain relapse lesions to be treated must measure =< 3.0 cm in maximal
extent and total volume of distant brain relapses to be treated must measure < 30
mL on the contrast-enhanced diagnostic magnetic resonance imaging (MRI) brain
scan obtained within 21 days prior to randomization
• Distant brain relapse lesions must be diagnosed on MRI, which will include the
following elements:
• REQUIRED MRI ELEMENTS
• Post gadolinium contrast-enhanced T1-weighted three-dimensional (3D)
spoiled gradient (SPGR). Acceptable 3D SPGR sequences include
magnetization-prepared 3D gradient recalled echo (GRE) rapid gradient
echo (MP-RAGE), turbo field echo (TFE) MRI, BRAVO (brain volume
imaging) or 3D fast FE (field echo). The T1-weighted 3D scan should use
the smallest possible axial slice thickness, not to exceed 1.5 mm
• Pre-contrast T1 weighted imaging (3D imaging sequence strongly
encouraged)
• A minimum of one axial T2 fluid attenuated inversion recovery (FLAIR)
(preferred) or T2 sequence is required. This can be acquired as a 2D or
3D image. If 2D, the images should be obtained in the axial plane
• ADDITIONAL RECOMMENDATIONS
• Recommendation is that an axial T2 FLAIR (preferred) sequence be
performed instead of a T2 sequence
• Recommendation is that that pre-contrast 3D T1 be performed with the
same parameters as the post-contrast 3D T1
• Recommendation is that imaging be performed on a 3 Tesla (3T) MRI
• Recommendation is that the study participants be scanned on the same
MRI instrument at each time point
• Recommendation is that if additional sequences are obtained, these
should meet the criteria outlined in Kaufmann et al., 2020
• If additional sequences are obtained, total imaging time should not
exceed 60 minutes
• Brain metastasis velocity (BMV) since upfront SRS must be >= 4 brain metastases/year
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry
• Pathologically (histologically or cytologically) proven diagnosis of non-small cell
lung cancer, melanoma, breast cancer, renal cell carcinoma, or gastrointestinal cancer
within 10 years prior to randomization. If the original histologic proof of malignancy
is greater than 10 years, then pathological (i.e., more recent) confirmation is
required (e.g., from a systemic metastasis or brain metastasis)
• Other histologies are not permitted
• History and physical examination within 28 days prior to randomization
• Karnofsky performance status of >= 70 within 28 days prior to randomization
• Calculated creatinine clearance (CrCl) >= 30 ml/min (within 28 days prior to
randomization)
• Blood urea nitrogen (BUN) within 1.5 times the institutional upper limit of normal
(ULN) (e.g., if the ULN is 20 mg/dL, then BUN up to 30 mg/dL is permitted) (within 28
days prior to randomization)
• Negative urine or serum pregnancy test (in women of childbearing potential) within 14
days prior to randomization
Exclusion Criteria:
• Prior WBRT or prophylactic cranial irradiation
• Local relapse of metastasis previously treated with upfront SRS (i.e., relapse outside
previously SRS-treated metastases is allowed)
• Brain metastases from primary germ cell tumor, small cell carcinoma, or lymphoma
• Definitive leptomeningeal metastasis
• Planned cytotoxic chemotherapy on the same day as SRS or HA-WBRT; concurrent
immunotherapy is permitted
• Radiographic evidence of enlargement or other architectural distortion of the lateral
ventricles, including placement of external ventricular drain or ventriculoperitoneal
shunt
• Known history of demyelinating disease such as multiple sclerosis
• Inability to swallow pills
• Contraindication to MR imaging such as non-MR conditional implanted metal devices or
unknown metallic foreign bodies, or contraindication to gadolinium contrast
administration during MR imaging, such as anaphylactic allergy that cannot be
adequately addressed with pre-contrast medications or acute kidney injury
• Contraindications to memantine, including:
• Allergy, including prior allergic reaction to memantine
• Intractable seizures on adequate anticonvulsive therapy-more than 1 seizure per
month for the past 2 months
• Current use of N-methyl-D-aspartate (NMDA) agonist
• Current alcohol or drug abuse, which can exacerbate lethargy/dizziness with
memantine
• Severe, active co-morbidity defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months
• Transmural myocardial infarction within the last 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of randomization
• Chronic obstructive pulmonary disease exacerbation or other acute respiratory
illness precluding study therapy at the time of randomization
• Severe hepatic disease defined as a diagnosis of Child-Pugh class B or C hepatic
disease
• Renal tubular acidosis or metabolic acidosis
• Human immunodeficiency virus (HIV) positive with CD4 count < 200
cells/microliter. Note that patients who are HIV positive are eligible, provided
they are under treatment with highly active antiretroviral therapy (HAART) and
have a CD4 count >= 200 cells/microliter within 30 days prior to randomization.
Note also that HIV testing is not required for eligibility for this protocol
• Pregnant or lactating women, or women of childbearing potential and men who are
sexually active and not willing/able to use medically acceptable forms of
contraception; this exclusion is necessary because the medication and radiation
involved in this study has unknown effects on the unborn fetus
Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Breast Carcinoma, Metastatic Digestive System Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Metastatic Malignant Neoplasm in the Brain, Metastatic Melanoma, Metastatic Renal Cell Carcinoma, Prognostic Stage IV Breast Cancer AJCC v8, Recurrent Brain Neoplasm, Stage IV Lung Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8, Brain and Nervous System, Brain/Central Nervous System
Vamikibart in Participants With Uveitic Macular Edema (Sandcat)
This study will assess the efficacy and safety of vamikibart in participants with uveitic
macular edema.
Laura Kopplin
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05642325
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Inclusion Criteria:
• Female participants: Agreement to remain abstinent (refrain from heterosexual
intercourse) or use contraception as defined by the protocol
• Diagnosis of macular edema associated with non-infectious uveitis (NIU)
• Diagnosis of active or inactive, acute, or chronic NIU of any etiology and of any
anatomical type (anterior, intermediate, posterior, panuveitis)
• BCVA letter score of 73 to 19 letters (inclusive) on Early Treatment Diabetic
Retinopathy Study (EDTRS)-like charts
Exclusion Criteria:
• Evidence of active or latent syphilis infection
• Evidence of active or latent tuberculosis infection and/or positive tuberculosis
assay, or previous or current HIV diagnosis
• Serious acute or chronic medical or psychiatric illness
• History of major ocular and non-ocular surgical procedures
• Uncontrolled IOP or glaucoma or chronic hypotony
• Any anatomical changes or media opacity in the study eye preventing evaluation of
retina, vitreous, and capture of study images
• Prior use of IVT biologics including anti-VEGFs less than 2-4 months prior to Day 1;
received IVT Methotrexate within 4 months prior to Day 1
• Prior macular laser therapy, cataract surgery within 6 months and laser capsulotomy
within 3 months of Day 1
• Topical corticosteroids and/or topical NSAID > 3 drops per day in the 14 days prior to
Day 1 (D1); intraocular or periocular corticosteroid injections in the 2 months prior
to D1; subconjunctival corticosteroid injection within 1 month prior to Day 1; an
OZURDEX implant in the 4 months prior to D1; YUTIQ, RETISERT or ILUVIEN implant in the
3 years prior to D1
• Diagnosis of macular edema due to any cause other than NIU
• Any major ocular conditions that may require medical or surgical intervention during
the study period to prevent vision loss
Melanoma Margins Trial-II: 1cm v 2cm Wide Surgical Excision Margins for AJCC Stage II Primary Cutaneous Melanoma (MelMarT-II)
Patients with a primary invasive melanoma are recommended to undergo excision of the primary
lesion with a wide margin. There is evidence that less radical margins of excision may be
just as safe. This is a randomised controlled trial of 1 cm versus 2 cm margin of excision of
the primary lesion for adult patients with stage II primary invasive cutaneous melanomas
(AJCC 8th edition) to determine differences in disease-free survival. A reduction in margins
is expected to improve patient quality of life.
Heather Neuman, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03860883
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Inclusion Criteria:
1. Patients must have a stage II primary invasive cutaneous melanoma with Breslow
thickness >2mm without ulceration), or >1mm (with ulceration only) (pT2b-pT4b, AJCC
8th edition) as determined by diagnostic biopsy (narrow excision, incision or punch
biopsy) and subsequent histopathological analysis.
2. Must have a primary melanoma that is cutaneous (including head, neck, trunk,
extremity, scalp, palm or sole).
3. An uninterrupted 2cm margin must be technically feasible around biopsy scar or primary
melanoma.
4. Surgery (which refers to the staging sentinel node biopsy and wide local excision as
these are both to be done on the same day) must be completed within 120 days of the
original diagnosis.
5. Patients must be 18 years or older at time of consent.
6. Patient must be able to give informed consent and comply with the treatment protocol
and follow-up plan.
7. Life expectancy of at least 5 years from the time of diagnosis, not considering the
melanoma in question, as determined by the PI.
8. Patients must have an ECOG performance score between 0 and 1.
9. A survivor of prior cancer is eligible provided that ALL of the following criteria are
met and documented:
• The patient has undergone potentially curative therapy for all prior
malignancies,
• There has been no evidence of recurrence of any prior malignancies for at least
FIVE years (except for successfully treated cervical or non-melanoma skin cancer
with no evidence of recurrence), and
• The patient is deemed by their treating physician to be at low risk of recurrence
from previous malignancies.
Exclusion Criteria:
Patients will be excluded from the study for ANY of the following reasons:
1. Uncertain diagnosis of melanoma i.e. so-called 'melanocytic lesion of unknown
malignant potential'.
2. Patient has already undergone wide local excision at the site of the primary index
lesion.
3. Patient unable or ineligible to undergo staging sentinel lymph node biopsy of the
primary index lesion.
4. Desmoplastic or neurotropic melanoma: with any patient where pathology determines
melanoma as PURE desmoplastic (as per WHO definition of >90% desmoplasia), they are
not eligible for this study. However other desmoplasia or mixed subtypes are eligible
unless there is neurotropism present (peri-neural invasion).Peri-neural invasion does
not include entrapment of nerves within the main primary tumour mass.
Microsatellitosis as per AJCC 8th edition definition
5. Subungual melanoma
6. Patient has already undergone a local flap reconstruction of the defect after excision
of the primary and determination of an accurate excision margin is impossible.
7. History of previous or concurrent (i.e., second primary) invasive melanoma.
8. Melanoma located distal to the metacarpophalangeal joint; on the tip of the nose; the
eyelids or on the ear; genitalia, perineum or anus; mucous membranes or internal
viscera.
9. Physical, clinical, radiographic or pathologic evidence of satellite, in-transit,
regional, or distant metastatic melanoma.
10. Patient has undergone surgery on a separate occasion to clear the lymph nodes of the
probable draining lymphatic field, including sentinel lymph node biopsy, of the index
melanoma.
11. Any additional solid tumour or hematologic malignancy during the past 5 years except
T1 skin lesions of squamous cell carcinoma, basal cell carcinoma, or uterine/cervical
cancer.
12. Melanoma-related operative procedures not corresponding to criteria described in the
protocol.
13. Planned adjuvant radiotherapy to the primary melanoma site after Wide Local Excision
is not permitted as part of the protocol and any patients given this treatment would
be excluded from the study.
14. History of organ transplantation.
15. Oral or parenteral immunosuppressive agents (not topical or inhaled steroids) at
enrolment or within 6 months prior to enrolment.
Pregnancy is not a specific exclusion criterion for this trial, though it may not be
clinically appropriate to perform a wide excision and sentinel node biopsy until the
pregnancy has been completed, which is likely to exclude the patient due to violation of
inclusion criterion 4. We would advise careful counselling of the patient prior to
enrolling the patient, which would include a discussion at the treating centre's
multidisciplinary team meeting or tumour board. We would strongly advise contacting the
central trial office to discuss the case prior to enrolling on the study.
Cutaneous Melanoma, Stage II, Melanoma, Skin, Melanoma/Skin cancer
Protonix Treatment of Maintenance of Healing in Pediatric Participants Aged 1-11 Years and 12-17 Years
The purpose of this study is to explore the outcomes, tolerability and safety of 2 different
doses of oral pantoprazole (full healing dose, half healing dose), assigned based upon
weight, for the maintenance of healing of erosive esophagitis in pediatric participants aged
1 to 17 years with endoscopically-confirmed, healed erosive esophagitis.
Thomas Ratchford
All
1 Year to 17 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT04821310
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Inclusion Criteria:
• Participants must have a documented erosive lesion with an Los Angeles (LA) Grade of A
to D prior to starting Proton Pump Inhibitor treatment:
• Capable of giving signed informed consent/assent
• Willingness and ability of the participant or parent/legal guardian to complete the
eDiary
• Willing and able to comply with all scheduled visits, treatment plan, laboratory
tests, lifestyle considerations, and other study procedures, including the use of the
eDiary.
• Male and female participants aged 1 to 17 years.
• Minimum body weight 7 kilogram and weight at least at the 5th percentile per the
Center for Disease Control standard age and weight chart, for the participant's age.
• To be considered a female of non childbearing potential, the participant must meet at
least 1 of the following criteria :
• Premenarchal: The investigator (or other appropriate staff) must discuss the
participant's premenarchal status with the participant and parent/legal guardian at
office visits and during telephone contacts, as participants who achieve menarche
during the study would no longer be considered "female participants of non
childbearing potential" and must comply with the protocol requirements applicable to
women of childbearing potential.
Exclusion Criteria:
• Previous administration of an investigational drug or vaccine within 30 days (or as
determined by the local requirement) or 5 half-lives preceding the first dose of study
intervention used in this study (whichever is longer).
• Children that may be at high risk from procedural sedation should be carefully
evaluated. Participants with a history of complications during prior procedural
sedation
• History or presence of upper gastrointestinal anatomic or motor disorders
• Family history of malignant hyperthermia
• Known hypersensitivity to any Proton Pump Inhibitor, including pantoprazole or to any
substituted benzimidazole or to any of the excipients.
• Any disorder requiring chronic (daily) use of warfarin, heparin, other anticoagulants,
methotrexate, atazanavir or nelfinavir, clopidogrel, or potent inhibitors or inducers
of CYP2C19 (eg, phenytoin, sulfamethoxazole, valproic acid, carbamazepine, and
griseofulvin).
• Serum creatine kinase levels >3 x upper limit of normal.
• Known history of human immunodeficiency virus or clinical manifestations of acquired
immune deficiency syndrome.
• Active malignancy of any type, or history of a malignancy. Participants with a history
of malignancies that have been surgically removed or eradicated by irradiation or
chemotherapy and who have no evidence of recurrence for at least 5 years before
Screening are acceptable.
• Diagnosed as having or has received treatment for esophageal, gastric, pyloric
channel, or duodenal ulceration within 30 days before the Screening visit.
• Alanine aminotransferase or blood urea nitrogen >2.0 upper limit of normal or
estimated creatinine >1.5 X upper limit of normal for age or any other laboratory
abnormality considered by the Investigator to be clinically significant within 14 days
before the Baseline Visit (Day 1).
• Other acute or chronic medical or psychiatric condition including recent (within the
past year) or active suicidal ideation or behavior or laboratory abnormality that may
increase the risk associated with study participation or study intervention
administration or may interfere with the interpretation of study results and, in the
judgment of the investigator, would make the participant inappropriate for entry into
this study.
• Has, in the Investigator's opinion, a serious chronic condition (eg, diabetes,
epilepsy), which is either not stable or not well controlled and may interfere with
the conduct of the study.
• Has any condition possibly affecting drug absorption (eg, gastrectomy).
Prior or Concomitant Therapy:
• Frequent, repeated use of oral or parenteral glucocorticoids (eg, prednisone,
prednisolone, dexamethasone). Steroid inhalers and topical steroids may be used.
• Pregnant female participants; breastfeeding female participants.
• Is unwilling or unable to comply with the Lifestyle Considerations section
IPH5201 and Durvalumab in Patients With Resectable Non-Small Cell Lung Cancer (MATISSE)
The study is intended to assess the safety and efficacy of neoadjuvant combination of IPH5201
and durvalumab in addition to standard chemotherapy and adjuvant combination of IPH5201 and
durvalumab in untreated patients with resectable, early-stage (stage II to IIIA) non-small
cell lung cancer (NSCLC).
Vincent Ma, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05742607
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Inclusion Criteria:
1. Newly diagnosed and previously untreated patients with histologically or cytologically
documented NSCLC resectable (Stage IIA to Stage IIIA) disease (according to Version 8
of IASLC Staging Manual in Thoracic Oncology 2016.
2. WHO Performance Status or Eastern Cooperative Oncology Group of 0 or 1.
3. Adequate organ and marrow function.
4. Must have a life expectancy of at least 12 weeks.
5. Body weight > 35 kg.
6. Females of childbearing potential should use an acceptable method of contraception
from the time of screening throughout the total duration of the study.
7. Negative pregnancy test (serum or urine) for women of childbearing potential.
8. Provision of tumor samples (newly acquired [preferred] or archival tumor tissue [≤ 6
months old]) to confirm Programmed Death-Ligand 1 status, Epidermal Growth Factor
Receptor, or Anaplastic Lymphoma Kinase status.
9. Provision of tumor samples appropriate for exploratory biomarker analyses.
10. Patients will be suitable for inclusion if the planned surgery to be performed will be
lobectomy, sleeve resection, or bilobectomy, as determined by the attending surgeon
based on the baseline findings.
11. A pre- or post-bronchodilator FEV1 of 1.0 L and DLCO > 40% postoperative predicted
value.
Exclusion Criteria:
1. Participants with sensitising EGFR mutations or ALK translocations.
2. History of allogeneic organ transplantation.
3. Active or prior documented autoimmune or inflammatory disorders.
4. Uncontrolled intercurrent illness, uncontrolled hypertension, unstable angina
pectoris, uncontrolled cardiac arrhythmia, active ILD, serious chronic
gastrointestinal conditions associated with diarrhoea, or psychiatric illness/social
situations that would limit compliance with study requirement.
5. History of any grade of venous or arterial thromboembolic events including
cerebrovascular accident, transient ischemic attack, or unstable angina pectoris
within 6 months prior to enrollment.
6. History of another primary malignancy.
7. Patients with small-cell lung cancer or mixed small-cell lung cancer.
8. History of active primary immunodeficiency.
9. Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and tuberculosis testing in
line with local practice), hepatitis B (known positive HBsAg result) and HCV. Patients
with a past or resolved HBV infection (defined as the presence of hepatitis B core
antibody and absence of HBsAg) are eligible. Patients positive for HCV antibody are
eligible only if PCR is negative for HCV RNA.
10. Patients who have preoperative radiotherapy treatment as part of their care plan.
11. Patients who require or may require pneumonectomy, segmentectomies, or wedge
resections, as assessed by their surgeon, to obtain potentially curative resection of
primary tumor.
12. QTc interval ≥ 470 ms (NOTE: If prolonged, then 2 additional ECGs should be obtained
and the average QTcF interval should be used to determine eligibility).
13. Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients.
14. Any medical contraindication to treatment with chemotherapy as listed in the local
labelling.
15. Patients with moderate or severe cardiovascular disease.
16. Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy
for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related
conditions (e.g., hormone replacement therapy) is acceptable.
17. Receipt of live attenuated vaccine within 30 days prior to the first dose of study
interventions.
18. Major surgical procedure (as defined by the Investigator) within 30 days prior to the
first dose of study drugs.
19. Prior exposure to immune-mediated therapy.
20. Current or prior use of immunosuppressive medication within 14 days before the first
dose of study drugs.
21. Participation in another clinical study with an investigational product administered
within 30 days prior to enrolment.
22. Previous study drugs (durvalumab, IPH5201) assignment in the present study.
23. Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 180 days after the last dose of study drugs administration.
24. Involvement in the planning and/or conduct of the study (applies to both company staff
and/or staff at the study site).
25. Judgment by the Investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions and
requirements.
26. Exclusion criteria for participation in the optional (DNA) genetics research
component.
A Study of Camizestrant in ER+/HER2- Early Breast Cancer After at Least 2 Years of Standard Adjuvant Endocrine Therapy (CAMBRIA-1)
This is a Phase III open-label study to assess if camizestrant improves outcomes compared to
standard endocrine therapy in patients with ER+/HER2 - early breast cancer with intermediate
or high risk for disease recurrence who completed definitive locoregional therapy (with or
without chemotherapy) and standard adjuvant endocrine therapy (ET) for at least 2 years and
up to 5 years. The planned duration of treatment in either arm of the study is 60 months.
Kari Wisinski, MD
All
18 Years to 130 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT05774951
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Inclusion Criteria:
• Women and Men, ≥18 years at the time of screening (or per national guidelines)
• Histologically confirmed ER+/HER2- early-stage resected invasive breast cancer with
high or intermediate risk of recurrence, based on clinical-pathological risk features,
as defined in the protocol.
• Completed adequate (definitive) locoregional therapy (surgery with or without
radiotherapy) for the primary breast tumour(s), with or without (neo)adjuvant
chemotherapy
• Completed at least 2 years but no more than 5 years (+3 months) of adjuvant ET (+/-
CDK4/6 inhibitor)
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
• Adequate organ and marrow function
Exclusion criteria:
• Inoperable locally advanced or metastatic breast cancer
• Pathological complete response following treatment with neoadjuvant therapy
• History of any other cancer (except non-melanoma skin cancer or carcinoma in situ of
the cervix or considered at very low risk of recurrence per investigator judgement)
unless in complete remission with no therapy for a minimum of 5 years from the date of
randomisation
• Any evidence of severe or uncontrolled systemic diseases which, in the investigator's
opinion precludes participation in the study or compliance
• Known LVEF <50% with heart failure NYHA Grade ≥2.
• Mean resting QTcF interval >480 ms at screening
• Concurrent exogenous reproductive hormone therapy or non-topical hormonal therapy for
non-cancer-related conditions
• Any concurrent anti-cancer treatment not specified in the protocol with the exception
of bisphosphonates (e.g. zoledronic acid) or RANKL inhibitors (eg, denosumab)
• Previous treatment with camizestrant, investigational SERDs/investigational ER
targeting agents, or fulvestrant
• Currently pregnant (confirmed with positive serum pregnancy test) or breastfeeding
• Patients with known hypersensitivity to active or inactive excipients of camizestrant
or drugs with a similar chemical structure or class to camizestrant. In
pre-/peri-menopausal female and male patients, known hypersensitivity or intolerance
to LHRH agonists, that would preclude the patient from receiving any LHRH agonist
The ACCEL® Absorbable Hemostat Powder Clinical IDE Trial is designed as a prospective,
multi-center, randomized, non-inferiority, controlled pivotal clinical trial to evaluate the
safety and efficacy of the ACCEL® Absorbable Hemostat Powder as compared to gelatin sponge,
for achieving hemostasis in subjects undergoing cardiovascular, liver, or soft tissue
surgery, when control of oozing to moderate bleeding by standard surgical techniques is
ineffective and/or impractical.
Chris Rokkas
All
22 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT04728087
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Inclusion Criteria:
Pre-Surgery:
1. Subject is greater than or equal to 22 years old
2. Subject is undergoing a cardiovascular surgery, liver surgery or soft tissue surgical
procedure
3. Subject is willing and able to provide appropriate (Institutional Review Board (IRB)
approved) informed consent.
4. The subject is willing and able to comply with the requirements of the protocol,
including follow-up evaluations and schedule.
5. The subject is willing to be treated with ACCEL® Absorbable Hemostat Powder
6. The subject is willing to be treated with a commercially available absorbable gelatin
sponge
During Surgery:
7. Subject has not received blood transfusions between screening and application of
investigational product or commercially available absorbable gelatin sponge
8. There is an estimated TBS surface area of ≤ 60 cm2
9. Visual observation of oozing (0.01 g/10s ˂ Flow ˂ 0.04 g/10s), mild (0.04 g/10s ≤ Flow
˂ 0.32 g/10s), or moderate (0.32 g/10s ≤ Flow ˂ 1.01 g/10s) bleeding as validated and
when control by conventional surgical techniques, including but not limited to suture,
ligature and cautery, is ineffective and/or impractical
10. There is an absence of intra-operative complications other than bleeding, which, in
the opinion of the Investigator, may interfere with the assessment of efficacy or
safety
11. There has been no intra-operative use of adjunct hemostat(s) on the target bleeding
site identified for application of the study treatment
Exclusion Criteria:
Pre-Surgery:
1. The subject is pregnant (verified in a manner consistent with institution's standard
of care)
2. Subject is lactating
3. Subject is currently participating in another investigational device or drug trial or
has participated in one in the past 4 weeks (prior to surgery) or is planning to
participate in another research study involving any investigational product within 4
weeks after surgery
4. Subject is a prisoner, a minor or unable to adequately give informed consent due to
mental or physical condition
5. Subject has medical, social, or psychosocial issues that the Investigator believes
could impact the subject's safety or compliance with study procedures
6. Subject has a known allergy to potatoes
7. Subject has a known allergy to porcine collagen/gelatin
8. Subject has a religious or other objection to porcine products
9. Subject is unwilling to receive blood products
10. Subject has history of heparin-induced thrombocytopenia (only for cardiovascular
subjects where heparin use is required)
11. Subject with a baseline abnormality of INR > 2.5 or an aPTT> 100 seconds during
screening that is not explained by current drug treatment (e.g. heparin, warfarin,
etc.).
12. Subjects with platelets < 100 X 109 PLT/L during screening
13. Subject with Aspartate Aminotransferase (AST) or Alanine aminotransferase (ALT) > 3 X
upper limit normal range during screening, except for subjects undergoing liver
resection surgery or with a diagnosis of liver metastases where there is no upper
limit normal for these analytes due to the nature of their disease
14. Subject is unwilling or unable to return for the required follow-up after surgery
During Surgery:
15. Subject has an operative bleeding site which the surgeon is unable or unwilling to
control with a hemostatic agent
16. Extracorporeal cardiopulmonary bypass circuits or blood salvage circuits are to be
used during or after identification of the TBS.
17. There has been intra-operative use of thrombin on the patient.
Testing the Use of the Combination of Selumetinib and Olaparib or Selumetinib Alone Targeted Treatment for RAS Pathway Mutant Recurrent or Persistent Ovarian and Endometrial Cancers, A ComboMATCH Treatment Trial
This phase II ComboMATCH treatment trial compares selumetinib plus olaparib to selumetinib
alone in women with endometrial or ovarian (fallopian tube and primary peritoneal) cancer
that has come back (recurrent) or that remains despite treatment (persistent) and harbors a
mutation in the RAS pathway. Selumetinib may stop the growth of tumor cells by blocking some
of the enzymes needed for cell growth. Olaparib is an inhibitor of PARP, an enzyme that helps
repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep tumor
cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of
targeted therapy. The addition of olaparib to selumetinib could increase the percentage of
tumors that shrink as well as lengthen the time that the tumors remain stable (without
progression) as compared to selumetinib alone.
Janelle Sobecki, MD
Female
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05554328
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Inclusion Criteria:
• Patient must have enrolled onto EAY191 and must have been given a treatment assignment
to ComboMATCH to EAY191-N4 based on the presence of an actionable mutation as defined
in EAY191
• Patients must be enrolled on the ComboMATCH Master Registration Trial EAY191
• Patients must have RAS pathway mutations as determined by the ComboMATCH screening
assessment
• Cohort 1: Patients with histologically confirmed RAS pathway mutant ovarian,
primary peritoneal, or fallopian tube ("ovarian") cancer (activating mutations in
KRAS, NRAS, HRAS, BRAF, MEK1, MEK2, or inactivating mutations in NF1)
• Cohort 2: Patients with histologically confirmed RAS pathway mutant endometrial
cancer (activating mutations in KRAS, NRAS, HRAS, BRAF, MEK1, MEK2, or
inactivating mutations in NF1).
• Patients must have disease that can be safely biopsied and agree to a pre-treatment
biopsy, if disease cannot be safely biopsied, or have archival tissue available from
within 12 months prior to registration on the ComboMATCH Registration Trial (EAY191)
• Patients must have progressed after first-line treatment for recurrent or persistent
disease
• Patients with ovarian cancer should not be eligible for further platinum-based therapy
• Patients with endometrial cancer must have received or been offered an immune oncology
agent (alone or in combination with lenvatinib) unless there are existing
contraindications for immune oncology agents or lenvatinib
• Patients may have received unlimited prior therapy
• Patients must have measurable and biopsiable disease. Measurable disease is defined by
RECIST 1.1 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 CT, magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >
20 mm when measured by chest x-ray. Lymph nodes must be > 15 mm in short axis when
measured by CT or MRI
• Patients must have at least one "target lesion" separate from the lesion to be
biopsied to be used to assess response on this protocol as defined by RECIST
version 1.1. Tumors within a previously irradiated field will be designated as
"non-target" lesions unless progression is documented or a biopsy is obtained to
confirm persistence at least 90 days following completion of radiation therapy
• Prior therapy must have been completed at least four weeks prior to registration
• Age >= 18
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
• Hemoglobin (Hgb) >= 9.5 g/dL with no blood transfusion in the past 28 days (within 14
days prior to registration)
• Platelets >= 100,000/mcl (within 14 days prior to registration)
• Absolute neutrophil count (ANC) >= 1,500/mcl (within 14 days prior to registration)
• Patients must have creatinine clearance estimated of >= 50 mL/min using the
Cockcroft-Gault equation or based on a 24 hour urine test (within 14 days prior to
registration)
• Total bilirubin level =< 1.5 x institutional upper limit of normal (ULN) or =< 3 x ULN
in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia)
(within 14 days prior to registration)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (within
14 days prior to registration)
• Patients must be able to swallow and retain oral medications and be without
gastrointestinal illnesses that would preclude absorption of selumetinib or olaparib
• 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
• Women of childbearing potential (WOCBP) must agree to use two forms of birth control
(hormonal or barrier method of birth control; abstinence) during the study and for 12
weeks after completing treatment
• Non-sterilized male partners of WOCBP (including males sterilized by a method
other than bilateral orchidectomy e.g., vasectomy) who intend to be sexually
active with a female partner must be using an acceptable method of contraception
such as male condom plus spermicide (condom alone in countries where spermicides
are not approved) from the time of screening throughout the total duration of the
study and the drug washout period (at least 16 weeks after the last dose of study
intervention) to prevent pregnancy in a partner. Periodic abstinence, the rhythm
method, and the withdrawal method are not acceptable methods of contraception.
Vasectomized (i.e., sterile) males are considered fertile and should still use a
male condom plus spermicide as indicated above during the clinical study
• 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
• 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
• 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 new or progressive brain metastases (active brain metastases) or
leptomeningeal disease are eligible if the treating physician determines that
immediate central nervous system (CNS) specific treatment is not required and is
unlikely to be required during the first cycle of therapy
• Patients with treated brain metastases are eligible if follow-up brain imaging
after CNS-directed therapy shows no evidence of progression
• Extra caution should be taken with olaparib, as it crosses the blood brain
barrier and can cause edema in brain metastases
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry and, for patients treated in the United States
(U.S.), authorization permitting release of personal health information
Exclusion Criteria:
• Patients who have received any MEK inhibitors
• Patients who have progressed while receiving a PARP inhibitor
• Patients who have received chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to registration
• Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual toxicities > grade 1) with the exception of alopecia
• Patients with uncontrolled intercurrent illness
• Patients with >= grade 2 neuropathy within 14 days of registration
• Patients with severe (Child-Pugh C) liver dysfunction
• Patients with a history of allergic reactions attributed to compounds of similar
chemical or biologic composition to olaparib and selumetinib or any excipients thereof
• Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin,
rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or
moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout
period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3
weeks for other agents
• Supplementation with vitamin E greater than 100% of the daily recommended dose.
Any multivitamin containing vitamin E must be stopped prior to study enrollment
even if less than 100% of the daily recommended dosing for vitamin E
• Vitamin E must not be taken in the 7 days prior to initiation of treatment with
selumetinib
• Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin,
clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,
saquinavir, nelfinavir, boceprevir, telaprevir) or known moderate CYP3A inhibitors
(e.g. ciprofloxacin, erythromycin, diltiazem, Fluconazole, verapamil). The required
washout period prior to starting olaparib is at least 14 days or 5 half-lives
(whichever is longer) before the first dose of study medication
• Concomitant use of strong CYP2C19 inhibitors (e.g., ticlopidine) or moderate CYP2C19
inhibitors (e.g., omeprazole). The required washout period prior to starting
selumetinib is at least 14 days or 5 half-lives (whichever is longer) before the first
dose of study medication
• Have received or are receiving an investigational medicinal product (IMP) or other
systemic anti-cancer treatment (including chemotherapy, immunotherapy, targeted
therapy, biologic therapy, tumor embolization, or monoclonal antibodies) within 4
weeks prior to registration, or within a period during which the IMP or systemic
target treatment has not been cleared from the body (e.g., a period of 5
'half-lives'), whichever is longer
• Known myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of
myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
• Patients who have had previous organ transplant, allogenic bone marrow transplant or
double umbilical cord blood transplantation
• Patients who have had whole blood transfusion within 28 days prior to registration
• Patients with ophthalmological conditions as follows:
• Current or past history of retinal pigment epithelial detachment/central serous
retinopathy or retinal vein occlusion.
• Intraocular pressure >21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma
(irrespective of intraocular pressure [IOP]). Subjects with known glaucoma and
increased IOP who do not have meaningful vision (light perception only or no
light perception) and are not experiencing pain related to the glaucoma, may be
eligible after discussion with the study chair
• Patients with any other significant abnormality on ophthalmic examination should
be discussed with the study chair for potential eligibility
• Ophthalmological findings secondary to long-standing optic pathway glioma (such
as visual loss, optic nerve pallor or strabismus) or longstanding orbito-temporal
plexiform neurofibroma (PN) (such as visual loss, strabismus) will NOT be
considered a significant abnormality for the purposes of the study
• Patients with severe, active co-morbidity defined as any of the following:
• History and/or confirmed pneumonitis
• Uncontrolled hypertension (blood pressure [BP] >= 150/90 mmHg despite medical
therapy)
• Acute coronary syndrome within 6 months prior to registration
• Uncontrolled atrial fibrillation
• Known family history of long QT syndrome
• Women who are pregnant or unwilling to discontinue nursing
*Note: Email is generally not a secure way to communicate sensitive or health-related information as there are many ways for unauthorized users to access email. You should avoid sending sensitive, detailed personal information by email.