Ovarian Cancer Clinical Trial
Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial
Summary
This ComboMATCH patient registration trial is the gateway to a coordinated set of clinical trials to study cancer treatment directed by genetic testing. Patients with solid tumors that have spread to nearby tissue or lymph nodes (locally advanced) or have spread to other places in the body (advanced) and have progressed on at least one line of standard systemic therapy or have no standard treatment that has been shown to prolong overall survival may be candidates for these trials. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with some genetic changes or abnormalities (mutations) may benefit from treatment that targets that particular genetic mutation. ComboMATCH is designed to match patients to a treatment that may work to control their tumor and may help doctors plan better treatment for patients with locally advanced or advanced solid tumors.
Full Description
PRIMARY OBJECTIVE:
I. To register, allocate, and assign patients to ComboMATCH treatment trials.
SECONDARY OBJECTIVES:
I. To evaluate the rate of positive outcomes in defined cohorts within treatment trials of treatment combinations including targeted therapies for molecularly defined populations, and also in the subset of treatment trials where the treatments are supported by in vivo models.
II. To perform quality control of the patients registered in the form of pathological confirmation of disease and sub-type to confirm diagnosis and treatment arm allocation.
SECONDARY CORRELATIVE OBJECTIVES:
I. Assess the concordance of the central molecular characterization of the pre-treatment biopsy samples with the genetic readouts from the Designated Laboratories (DLs) for patients enrolled on the ComboMATCH treatment trials.
II. To assess how the registration diagnostic tumor mutation profile and pre-treatment biopsy profile compare to the circulating tumor-derived deoxyribonucleic acid (ctDNA) mutation profile from plasma.
EXPLORATORY OBJECTIVE:
I. Assess association between ComboMATCH treatment trials outcomes (positive or negative) with the type of rationale for the selected drug combinations and the type of rationale for the gene variant/combination for selection (e.g., whether the trial was based on targeted therapies for molecularly defined populations, those that were supported by in vivo models, and those that were supported by empiric clinical data).
OUTLINE:
REGISTRATION: Patients undergo tumor mutational screening of previously-collected tumor samples for specific, pre-defined mutations, amplifications, or translocations of interest via tumor sequencing. Patients who are 18 years or older and have biopsiable disease undergo a new biopsy for research purposes prior to initiating treatment on the ComboMATCH treatment trial.
TREATMENT: Patients with mutations targeted to investigational combination therapies are assigned to 1 of 20 treatment subprotocols.
EAY191-N4: Patients with RAS pathway mutant ovarian or endometrial cancer are randomized to 1 of 2 arms.
ARM I: Patients receive selumetinib PO and olaparib PO on study. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as echocardiogram (ECHO) or multigated acquisition (MUGA), and computed tomography (CT) scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated.
ARM II: Patients receive selumetinib PO on study. Patients who experience progression may elect to cross over to Arm I provided they have not had dose limiting toxicities to monotherapy selumetinib. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as ECHO or MUGA, and CT scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated.
EAY191-N2: Patients with NF1 nonsense or frameshift mutations or NF1 gene deletion, and hormone receptor positive, HER2-negative metastatic breast cancer. Patients who are fulvestrant naive are assigned to Cohort I, while patients who are fulvestrant resistant are assigned to Cohort II.
COHORT I: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive fulvestrant intramuscularly (IM) and binimetinib PO throughout the trial. Patients also undergo a CT, magnetic resonance imaging (MRI), or bone scan and tumor biopsy during screening and on study.
ARM II: Patients receive fulvestrant IM throughout the trial. Patients who progress on fulvestrant alone are asked to reaffirm their willingness to enroll in cohort II. Patients not willing to transition to cohort II continue further therapy as clinically indicated. Patients undergo a CT, MRI, or bone scan and tumor biopsy during screening and on study.
COHORT II: Patients receive fulvestrant IM and binimetinib PO throughout the trial. If the patient progressed on fulvestrant, the loading dose of fulvestrant is omitted. Patients undergo a CT, MRI, or bone scan and tumor biopsy during screening and on study.
EAY191-E4: Patients with solid tumors who previously underwent taxane therapy.
Patients receive nilotinib hydrochloride monohydrate PO twice daily (BID) on days 1-28 and paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI during screening or cycle 1 day 1, every 2 cycles for 1 year, every 3 cycles for patients on study for more than 1 year, and every 4 cycles for patients on study for more than 3 years and may also undergo CT or MRI during follow-up every 3 months for 2 years and then every 6 months for 1 year if clinically indicated. Patients also undergo collection of blood samples at baseline, cycle 2 day 1, and optionally at progression as well as tumor biopsy at baseline and optionally at progression.
EAY191-A3: Patients with KRAS/NRAS/BRAF mutated low-grade serous ovarian cancer (LGSOC) naive to MEK or CDK4/6 inhibitor therapy are randomized to either combination cohort 1 or monotherapy cohort 1. Patients with LGSOC who have received prior MEK inhibitor therapy are assigned to combination cohort 2. Patients with KRAS/NRAS/HRAS/non-V600E BRAF mutated pancreatic cancer are assigned to combination cohort 3. Patients with all other KRAS/NRAS/HRAS mutated tumor types (excluding LGSOC, non-small cell lung cancer, colorectal cancer, pancreatic, and melanoma) are assigned to combination cohort 4.
COMBINATION COHORTS 1, 2, 3, 4: Patients receive palbociclib PO and binimetinib PO throughout the trial. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
MONOTHERAPY COHORT 1: Patients receive binimetinib PO throughout the trial. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
EAY191-S3: Patients with an activating AKT mutation solid tumor.
Patients receive paclitaxel IV and ipatasertib PO on study. Patients undergo a CT or MRI and blood collection throughout the trial. Patients also undergo a tumor biopsy during screening and follow-up.
EAY191-A6: Patients with RAS/RAF/MEK/ERK mutant biliary tract cancers are randomized to 1 of 2 arms.
ARM 1: Patients receive leucovorin IV, oxaliplatin IV, and fluorouracil IV on study. Patients undergo echocardiogram (ECHO) and multigated acquisition scan (MUGA) during screening and on study, a CT with contrast, MRI, or a fludeoxyglucose F-18 positron emission tomography (FDG-PET) during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated.
ARM 2: Patients receive binimetinib PO, leucovorin IV, oxaliplatin IV, and fluorouracil IV on study. Patients undergo ECHO and MUGA during screening and on study, a CT with contrast, MRI, or an FDG-PET during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated
EAY191-E5: Patients are assigned to 1 of 2 cohorts.
COHORT I: Patients who have never received a KRAS G12C inhibitor randomized to arms A or B.
ARM A: Patients receive sotorasib PO and panitumumab IV on study. Patients also undergo collection of blood samples and a tumor biopsy before treatment and CT or MRI at follow up.
ARM B: Patients receive sotorasib PO on study. Patients with disease progression may cross-over to cohort II. Patients also undergo collection of blood samples and a tumor biopsy before treatment and CT or MRI at follow up.
COHORT II: Patients who have received a KRAS G12C inhibitor assigned to arm C.
ARM C: Patients receive combination therapy as in Arm A.
Eligibility Criteria
Inclusion Criteria:
Patient must have measurable disease
Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status between 0-2 OR patient must have Lansky performance status of >= 50% or Karnofsky performance status of >= 50%
Patient must be deemed potentially eligible for a ComboMATCH Treatment Trial as assessed by the enrolling provider
All patients must have sequencing results available from a National Cancer Institute (NCI) credentialed Designated Laboratory (DL)
Patients must have locally advanced or advanced histologically documented solid tumors requiring therapy and meet one of the following criteria:
Patients must have progressed on at least one line of standard systemic therapy OR
Patients whose disease has no standard treatment that has been shown to prolong overall survival
Patient must meet one of the following requirements:
Patients 18 years and older who have tumor amenable to minimal risk image-guided or direct vision biopsy and must be willing and able to undergo a tumor biopsy to obtain samples for research if the patient is to enroll in a ComboMATCH treatment trial OR
Patients 18 years and older who do not have disease that is biopsiable at minimal risk to the patient must confirm availability of an archival tumor tissue specimen for submission for research if the patient enrolls to a ComboMATCH Treatment Trial. This tumor tissue must meet the following criteria:
Tissue must have been collected within 12 months prior to registration to the EAY191 Registration Trial
Patient must not have had a Response Evaluation Criteria in Solid Tumors (RECIST) response (complete response [CR] or partial response [PR]) to any intervening therapy after collection of the tissue
Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be available OR
Patients under 18 years old must confirm availability of an archival tumor tissue specimen for submission for research if patient enrolls to a ComboMATCH Treatment Trial. This tumor tissue must meet the following criteria:
Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be available
NOTE: See specific ComboMATCH Treatment Trial protocol for tissue collection and management instructions. Performance of the mandatory research biopsy or submission of pre-trial formalin-fixed paraffin-embedded (FFPE) and collection and submission of the blood specimens for the integrated studies will be performed under the consent authority of the specific treatment trial protocol to which the patient is registered. No procedures to collect specimens for research only are to be performed for patients registered to the EAY191 Registration Trial only
NOTE: Each ComboMATCH Treatment Trial contains specific eligibility criteria. If patient is found to not be eligible for the assigned ComboMATCH Treatment Trial, indication of ineligibility will trigger re-evaluation and potential assignment to another Treatment Trial
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There are 119 Locations for this study
Kingman Arizona, 86401, United States More Info
Principal Investigator
Arroyo Grande California, 93420, United States More Info
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Whittier California, 90602, United States More Info
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Newark Delaware, 19713, United States More Info
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Newark Delaware, 19713, United States More Info
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Boise Idaho, 83706, United States More Info
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Boise Idaho, 83712, United States More Info
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Caldwell Idaho, 83605, United States More Info
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Coeur d'Alene Idaho, 83814, United States More Info
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Fruitland Idaho, 83619, United States More Info
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Meridian Idaho, 83642, United States More Info
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Nampa Idaho, 83686, United States More Info
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Nampa Idaho, 83687, United States More Info
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Post Falls Idaho, 83854, United States More Info
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Sandpoint Idaho, 83864, United States More Info
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Twin Falls Idaho, 83301, United States More Info
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Bloomington Illinois, 61704, United States More Info
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Canton Illinois, 61520, United States More Info
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Carthage Illinois, 62321, United States More Info
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Danville Illinois, 61832, United States More Info
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Decatur Illinois, 62526, United States More Info
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Decatur Illinois, 62526, United States More Info
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Dixon Illinois, 61021, United States More Info
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Effingham Illinois, 62401, United States More Info
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Effingham Illinois, 62401, United States More Info
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Eureka Illinois, 61530, United States More Info
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Galesburg Illinois, 61401, United States More Info
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Kewanee Illinois, 61443, United States More Info
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Macomb Illinois, 61455, United States More Info
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Mattoon Illinois, 61938, United States More Info
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Ottawa Illinois, 61350, United States More Info
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Pekin Illinois, 61554, United States More Info
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Peoria Illinois, 61615, United States More Info
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Peru Illinois, 61354, United States More Info
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Princeton Illinois, 61356, United States More Info
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Springfield Illinois, 62702, United States More Info
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Springfield Illinois, 62702, United States More Info
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Springfield Illinois, 62781, United States More Info
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Urbana Illinois, 61801, United States More Info
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Washington Illinois, 61571, United States More Info
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Cedar Rapids Iowa, 52403, United States More Info
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Cedar Rapids Iowa, 52403, United States More Info
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Des Moines Iowa, 50314, United States More Info
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Lexington Kentucky, 40509, United States More Info
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New Orleans Louisiana, 70121, United States More Info
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Bethesda Maryland, 20892, United States More Info
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Cumberland Maryland, 21502, United States More Info
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Ann Arbor Michigan, 48106, United States More Info
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Brighton Michigan, 48114, United States More Info
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Brighton Michigan, 48114, United States More Info
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Canton Michigan, 48188, United States More Info
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Canton Michigan, 48188, United States More Info
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Chelsea Michigan, 48118, United States More Info
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Chelsea Michigan, 48118, United States More Info
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Flint Michigan, 48503, United States More Info
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Flint Michigan, 48503, United States More Info
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Flint Michigan, 48503, United States More Info
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Flint Michigan, 48503, United States More Info
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Livonia Michigan, 48154, United States More Info
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Ypsilanti Michigan, 48106, United States More Info
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Ypsilanti Michigan, 48197, United States More Info
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Edina Minnesota, 55435, United States More Info
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Minneapolis Minnesota, 55407, United States More Info
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Saint Paul Minnesota, 55102, United States More Info
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Cape Girardeau Missouri, 63703, United States More Info
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Anaconda Montana, 59711, United States More Info
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Billings Montana, 59101, United States More Info
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Bozeman Montana, 59715, United States More Info
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Great Falls Montana, 59405, United States More Info
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Kalispell Montana, 59901, United States More Info
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Missoula Montana, 59804, United States More Info
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Las Vegas Nevada, 89102, United States More Info
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Las Vegas Nevada, 89135, United States More Info
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Las Vegas Nevada, 89144, United States More Info
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Las Vegas Nevada, 89148, United States More Info
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Reno Nevada, 89502, United States More Info
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Middletown New Jersey, 07748, United States More Info
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Buffalo New York, 14263, United States More Info
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Commack New York, 11725, United States More Info
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Harrison New York, 10604, United States More Info
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New York New York, 10065, United States More Info
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Belpre Ohio, 45714, United States More Info
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Canton Ohio, 44710, United States More Info
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Chillicothe Ohio, 45601, United States More Info
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Columbus Ohio, 43213, United States More Info
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Columbus Ohio, 43219, United States More Info
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Lancaster Ohio, 43130, United States More Info
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Mount Vernon Ohio, 43050, United States More Info
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Newark Ohio, 43055, United States More Info
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Perrysburg Ohio, 43551, United States More Info
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Portsmouth Ohio, 45662, United States More Info
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Springfield Ohio, 45504, United States More Info
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Springfield Ohio, 45505, United States More Info
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Toledo Ohio, 43623, United States More Info
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Toledo Ohio, 43623, United States More Info
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Westerville Ohio, 43081, United States More Info
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Zanesville Ohio, 43701, United States More Info
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Newberg Oregon, 97132, United States More Info
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Ontario Oregon, 97914, United States More Info
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Oregon City Oregon, 97045, United States More Info
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Portland Oregon, 97213, United States More Info
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Portland Oregon, 97225, United States More Info
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Allentown Pennsylvania, 18103, United States More Info
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Altoona Pennsylvania, 16601, United States More Info
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Bethlehem Pennsylvania, 18017, United States More Info
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Bryn Mawr Pennsylvania, 19010, United States More Info
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East Stroudsburg Pennsylvania, 18301, United States More Info
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Erie Pennsylvania, 16505, United States More Info
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Greensburg Pennsylvania, 15601, United States More Info
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Mechanicsburg Pennsylvania, 17050, United States More Info
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Media Pennsylvania, 19063, United States More Info
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Monroeville Pennsylvania, 15146, United States More Info
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Paoli Pennsylvania, 19301, United States More Info
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Pittsburgh Pennsylvania, 15232, United States More Info
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Pittsburgh Pennsylvania, 15237, United States More Info
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Wynnewood Pennsylvania, 19096, United States More Info
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Providence Rhode Island, 02905, United States More Info
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Houston Texas, 77030, United States More Info
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Renton Washington, 98055, United States More Info
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Appleton Wisconsin, 54911, United States More Info
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Appleton Wisconsin, 54911, United States More Info
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Berlin Wisconsin, 54923, United States More Info
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La Crosse Wisconsin, 54601, United States More Info
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Madison Wisconsin, 53792, United States More Info
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Mukwonago Wisconsin, 53149, United States More Info
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Neenah Wisconsin, 54956, United States More Info
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New London Wisconsin, 54961, United States More Info
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Oconomowoc Wisconsin, 53066, United States More Info
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Oshkosh Wisconsin, 54904, United States More Info
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Shawano Wisconsin, 54166, United States More Info
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Waukesha Wisconsin, 53188, United States More Info
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Waupaca Wisconsin, 54981, United States More Info
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San Juan , 00927, Puerto Rico More Info
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