Study Stopped
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Olaparib and Alpelisib for Treatment of Metastatic Breast Cancer, A ComboMATCH Treatment Trial
Olaparib Plus Low-Dose Alpelisib for Breast Cancer: A ComboMATCH Treatment Trial
3 other identifiers
interventional
N/A
0 countries
N/A
Brief Summary
This phase II ComboMATCH treatment trial studies the effect of adding a drug called BYL719 (alpelisib) to the usual treatment of olaparib in patients with breast cancer that has spread from where it first started (breast) to other places in the body (metastatic). Olaparib is an inhibitor of PARP, an enzyme that helps repair 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. Alpelisib blocks certain proteins, which may help keep tumor cells from growing and may kill them. It is a type of kinase inhibitor. Giving alpelisib in combination with olaparib may be able to improve treatment results for patients with metastatic breast cancer.
Trial Health
Trial Health Score
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Started Oct 2023
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Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 28, 2023
CompletedFirst Posted
Study publicly available on registry
August 1, 2023
CompletedStudy Start
First participant enrolled
October 23, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
April 30, 2025
CompletedMarch 20, 2024
March 1, 2024
1.5 years
July 28, 2023
March 19, 2024
Conditions
Outcome Measures
Primary Outcomes (2)
Progression-free survival (PFS) (Cohort 2)
Will compare the PFS distributions between those treated with BYL719 (alpelisib) and olaparib versus (vs) olaparib. Despite this being a randomized phase II trial, we will utilize an intent to treat approach such that patients will be analyzed based on the treatment arm to which they were randomized. Will be compared between the two treatment arms using Kaplan-Meier methods. The hazard ratio, median PFS, and estimated PFS rates at 6, 12, 18, 24, and 30 months will be estimated along with corresponding 95% confidence intervals.
From randomization date until the time of disease progression or death due to any cause, assessed up to 5 years
Objective response rate (ORR) (Cohort 3)
Defined as the proportion of patients who documented a complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 divided by the total number of evaluable patients in a cohort.
Up to 5 years
Secondary Outcomes (6)
ORR (Cohort 2)
Up to 5 years
PFS (Cohort 3)
From study entry to the first of either disease progression or death from any cause, assessed up to 5 years
Overall survival (OS) (Cohorts 2 and 3)
From registration until death due to any cause, assessed up to 5 years
Clinical benefit rate (CBR) (Cohorts 2 and 3)
From registration until death due to any cause, assessed up to 5 years
Incidence of adverse events (Cohorts 2 and 3)
Up to 5 years
- +1 more secondary outcomes
Study Arms (4)
Cohort 1, Arm A (olaparib, alpelisib)
EXPERIMENTALPatients 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.
Cohort 2, Arm B (olaparib, alpelisib)
EXPERIMENTALPatients 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.
Cohort 2, Arm C (olaparib)
ACTIVE COMPARATORPatients 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.
Cohort 3, Arm D (olaparib, alpelisib)
EXPERIMENTALPatients 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.
Interventions
Given PO
Undergo biopsy
Undergo collection of blood
Undergo bone scans
Undergo CT
Undergo MRI
Given PO
Undergo PET
Eligibility Criteria
You may qualify if:
- Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-A2 based on the presence of an actionable mutation as defined in EAY191
- Metastatic or unresectable breast cancer that is HER2-negative (by American Society of Clinical Oncology-College of American Pathologists \[ASCO-CAP\] guidelines)
- Patients with estrogen receptor positive (ER+) or ER-negative disease are eligible
- Germline or deleterious somatic mutation in at least one of: BAP1, BARD1, BRCA1, BRCA2, BRIP1 (FANCJ), FANCA, FANCC, FANCD2, FANCE, FANCF, FANCM, MRE11,PALB2, RAD50, RAD51B, RAD51C, RAD51D
- COHORTS 1 AND 2 (PARP-INHIBITOR NAIVE): No prior PARP-inhibitor is allowed. Prior mTOR- or AKT-inhibitor is allowed
- COHORTS 1 AND 2 (PARP-INHIBITOR NAIVE): PIK3CA mutation status
- COHORT 3 (PRIOR PARP-INHIBITOR): Patient must have received and progressed on prior PARP inhibitor therapy in any setting; intervening lines of therapy are allowed
- At least one measurable lesion that can be accurately assessed at baseline by CT (MRI where CT is contraindicated) and is suitable for repeated assessment as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- Prior PI3K inhibitor therapy is allowed
- Patients with estrogen receptor positive (ER+) disease are eligible after progression on at least 1 prior endocrine treatment in the metastatic setting
- No treatment within 4 weeks of registration which includes: investigational medicinal product (IMP), systemic anti-cancer treatment (cytotoxic chemotherapy, immunotherapy, targeted therapy except for PI3K inhibitors, biologics, tumor embolization, or monoclonal antibodies). If there is a period needed for the IMP or systemic treatment to be cleared from the body that may take longer than 4 weeks (i.e. period of 5 half lives), the longer time period should be utilized
- No major surgery done =\< 14 days prior to registration, or patients must have recovered from any effects from any major surgery that occurred \> 14 days prior to registration
- 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 and an agent that has known genotoxic, mutagenic and teratogenic effects
- Therefore, for women of childbearing potential only, a negative pregnancy test done =\< 7 days prior to registration is required
- Age \>= 18 years
- +24 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Gerburg M Wulf
Alliance for Clinical Trials in Oncology
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 28, 2023
First Posted
August 1, 2023
Study Start
October 23, 2023
Primary Completion
April 30, 2025
Study Completion
April 30, 2025
Last Updated
March 20, 2024
Record last verified: 2024-03
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.