Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial : Molecular Analysis for Combination Therapy Choice (ComboMATCH)

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 once daily (QD) on days 1-28 and panitumumab intravenously IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study.ARM B: Patients receive sotorasib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross-over to cohort II. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study.COHORT II: Patients who have received a KRAS G12C inhibitor assigned to arm C.ARM C: Patients receive combination therapy as in Arm A.EAY191-A2: Patients are assigned to 1 of 3 cohorts.COHORT 1: PARP-inhibitor naive patients are assigned to Arm A.ARM A: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.COHORT 2: PARP-inhibitor naive patients are randomized to 1 of 2 a....

Medienart:	Klinische Studie

Erscheinungsjahr:	2024
Erschienen:	2024

Enthalten in:	ClinicalTrials.gov - (2024) vom: 02. Apr. Zur Gesamtaufnahme - year:2024

Sprache:	Englisch

Links:	Volltext [kostenfrei]

Themen:	610 Breast Neoplasms Carcinoma Endometrial Neoplasms Genital Neoplasms, Female Neoplasms Phase: Phase 2 Recruitment Status: Recruiting Recurrence Study Type: Interventional

Anmerkungen:	Source: Link to the current ClinicalTrials.gov record., First posted: October 3, 2022, Last downloaded: ClinicalTrials.gov processed this data on April 03, 2024, Last updated: April 03, 2024

Study ID:	NCT05564377 NCI-2022-06842 EAY191 U10CA180820
Veröffentlichungen zur Studie:

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PPN (Katalog-ID):	CTG000001627