Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial

Conditions

• Advanced Malignant Solid Neoplasm
• Anatomic Stage III Breast Cancer AJCC v8
• Anatomic Stage IV Breast Cancer AJCC v8
• Locally Advanced Malignant Solid Neoplasm
• Malignant Female Reproductive System Neoplasm
• Metastatic HER2-Negative Breast Carcinoma
• Metastatic Malignant Solid Neoplasm
• Recurrent Endometrial Carcinoma
• Recurrent Fallopian Tube Carcinoma
• Recurrent Malignant Female Reproductive System Neoplasm
• Recurrent Malignant Solid Neoplasm
• Recurrent Ovarian Carcinoma
• Recurrent Primary Peritoneal Carcinoma
• Unresectable HER2-Negative Breast Carcinoma
• Unresectable Malignant Solid Neoplasm

Eligibility Criteria

Sex

ALL

Age

N/A - N/A

Healthy Volunteers

Not accepted

Interventions

• Alpelisib — DRUG
  Given PO
• Binimetinib — DRUG
  Given PO
• Biopsy Procedure — PROCEDURE
  Undergo biopsy
• Biospecimen Collection — PROCEDURE
  Undergo blood collection
• Bone Marrow Aspiration — PROCEDURE
  Undergo bone marrow aspiration
• Bone Marrow Biopsy — PROCEDURE
  Undergo bone marrow biopsy
• Bone Scan — PROCEDURE
  Undergo bone scan
• Computed Tomography — PROCEDURE
  Undergo CT
• Echocardiography Test — PROCEDURE
  Undergo ECHO
• Fluorouracil — DRUG
  Given IV
• Fulvestrant — DRUG
  Given IM
• Ipatasertib — DRUG
  Given PO
• Leucovorin — DRUG
  Given IV
• Magnetic Resonance Imaging — PROCEDURE
  Undergo MRI
• Multigated Acquisition Scan — PROCEDURE
  Undergo MUGA
• Mutation Carrier Screening — PROCEDURE
  Undergo tumor mutational screening
• Neratinib Maleate — DRUG
  Given PO
• Nilotinib Hydrochloride Monohydrate — DRUG
  Given PO
• Olaparib — DRUG
  Given PO
• Oxaliplatin — DRUG
  Given IV
• Paclitaxel — DRUG
  Given PO or IV
• Palbociclib — DRUG
  Given PO
• Panitumumab — BIOLOGICAL
  Given IV
• Positron Emission Tomography — PROCEDURE
  Undergo PET
• Selumetinib Sulfate — DRUG
  Given PO
• Sotorasib — DRUG
  Given PO

Study Details

This ComboMATCH patient screening trial is the gateway to a coordinated set of clinical trials to study cancer treatment directed by genetic testing. Patients with solid tumors that have spread to nearby tissue or lymph nodes (locally advanced) or have spread to other places in the body (advanced) and have progressed on at least one line of standard systemic therapy or have no standard treatment that has been shown to prolong overall survival may be candidates for these trials. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with some genetic changes or abnormalities (mutations) may benefit from treatment that targets that particular genetic mutation. ComboMATCH is designed to match patients to a treatment that may work to control their tumor and may help doctors plan better treatment for patients with locally advanced or advanced solid tumors.

Key Dates

Start date

Apr 7, 2023

Status verified

Mar 2026

Primary completion

Jul 1, 2030

Completion

Jul 1, 2030

Study Design

Enrollment

2,900 participants (estimated)

Allocation

RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

SCREENING

Arms

• Experimental: EAY191-A2 (Cohort 1, Arm A)
  Cohort 1, 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 MDS or 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.
• Experimental: EAY191-A2 (Cohort 2, Arm B)
  Cohort 2, Arm B: 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 MDS or 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.
• Experimental: EAY191-A2 (Cohort 2, Arm C)
  Cohort 2, Arm C: Patients receive olaparib PO BID 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 MDS or AML. Patients experiencing disease progression have the option to migrate to Cohort 3, Arm D. 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.
• Experimental: EAY191-A2 (Cohort 3, Arm D)
  Cohort 3, Arm D: 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 MDS or 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.
• Experimental: EAY191-A3 Combo Cohorts 1, 2, 3, 4 (palbociclib, binimetinib)
  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.
• Experimental: EAY191-A3 Monotherapy Cohort 1 (binimetinib)
  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.
• Experimental: EAY191-A6 Arm I (RAS/RAF/MEK/ERK mutations)
  Patients receive 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 a 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.
• Experimental: EAY191-A6 Arm II (RAS/RAF/MEK/ERK mutations)
  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
• Experimental: EAY191-E4 (taxane therapy)
  Patients receive nilotinib hydrochloride monohydrate PO BID on days 1-28 and paclitaxel 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.
• Experimental: EAY191-E5 Cohort I Arm A (sotorasib, panitumumab)
  Patients receive sotorasib PO QD on days 1-28 and panitumumab 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.
• Active Comparator: EAY191-E5 Cohort I Arm B (sotorasib)
  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.
• Experimental: EAY191-E5 Cohort II (sotorasib)
  Patients receive combination therapy as in EAY191-E5 Arm A.
• Experimental: EAY191-N2 Cohort I (Arm I) (NF1 mutations)
  Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles and binimetinib PO BID on days 15 to 28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a CT, MRI, or bone scan, ECHO or MUGA, and tumor biopsy, as well as possible blood sample collection during screening and on study.
• Experimental: EAY191-N2 Cohort I (Arm II) (NF1 mutations)
  Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who progress on fulvestrant alone may migrate to cohort II if they meet the migration eligibility criteria. Patients not willing to migrate to cohort II will have further therapy at the investigator's discretion. Patients undergo a CT, MRI, or bone scan and tumor biopsy, as well as ECHO or MUGA and possible blood sample collection during screening and on study.
• Experimental: EAY191-N2 Cohort II (NF1 mutations)
  Patients receive fulvestrant IM on day 1 of each cycle and binimetinib PO BID on days 15-28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT, MRI, or bone scan, ECHO or MUGA and tumor biopsy, as well as possible blood sample collection during screening and on study.
• Experimental: EAY191-N4 Arm I (RAS pathway mutations)
  Patients receive selumetinib PO BID and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 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.
• Active Comparator: EAY191-N4 Arm II (RAS pathway mutations)
  Patients receive selumetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. 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.
• Active Comparator: EAY191-N5 Arm I (neratinib maleate)
  Patients receive neratinib maleate PO QD on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience progression may crossover to Arm II. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study.
• Experimental: EAY191-N5 Arm II (neratinib maleate,palbociclib)
  Patients receive neratinib maleate PO QD on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 and palbociclib PO QD on days 1-21 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study.
• Experimental: EAY191-S3 (activating AKT mutation)
  Patients receive paclitaxel IV on days 1, 8, and 15 and ipatasertib PO on days 1-21 of each cycle. Treatment repeats every 28 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI and blood collection throughout the trial. Patients also undergo a tumor biopsy during screening and optionally during follow-up.

Primary Outcome Measure

Accrual of patients to ComboMATCH treatment trials [ Time Frame: Up to 8 years ]

Locations (475)

Find similar trials in Birmingham, AL

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