Circulating Tumor DNA Enriched, Genomically Directed Post-neoadjuvant Trial for Patients With Residual Triple Negative Breast Cancer
- Conditions
- Triple Negative Breast CancerBreast Cancer
- Interventions
- Registration Number
- NCT04849364
- Lead Sponsor
- Bryan Schneider, MD
- Brief Summary
This is a 3-arm study stratified by plasma ctDNA. Patients with residual TNBC disease after pre-operative therapy will be assigned to 1 of 3 Arms based on plasma ctDNA positivity and genomic marker(s).
- Detailed Description
Participants that are plasma ctDNA positive with a genomic target will be assigned to one of the three groups in Arm 1 and receive genomically directed therapy.
* Arm 1a: DNA Repair pathway = talazoparib + capecitabine (CLOSED)
* Arm 1b: Immunotherapy pathway = pembrolizumab + capecitabine (CLOSED)
* Arm 1c: PI3K Pathway = inavolisib + capecitabine ---\> +/- standard of care pembrolizumab
* Arm 1d: DNA Repair + Immunotherapy = talazoparib + capecitabine +/- standard of care pembrolizumab
Participants that are plasma ctDNA positive without a genomic target will be assigned to Arm 2 and receive capecitabine and pembrolizumab or treatment of physician's choice.
Participants that are plasma ctDNA negative will be assigned to Arm 3 and receive any of the following based on patient and physician decision: no therapy/observation, capecitabine and pembrolizumab or treatment of physician's choice.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 197
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 3 Capecitabine Arm 3 subjects have plasma ctDNA negative. Treatment of patient and physician's choice will be given with consideration for capecitabine and pembrolizumab. Dose, schedule and duration of treatment to be determined by treating physician. Arm 1 Talazoparib Arm 1a: Patients who are ctDNA-positive and harbor a genomic target. DNA repair pathway = talazoparib + capecitabine (CLOSED) Arm 1b: Patients who are ctDNA-positive and harbor a genomic target. Immunotherapy pathway = pembrolizumab + capecitabine (CLOSED) Arm 1c: Patients who are ctDNA-positive and harbor a genomic target. PI3K Pathway = inavolisib + capecitabine ---\> +/- standard of care pembrolizumab Arm 1d: Patients who are ctDNA-positive and harbor a genomic target. DNA Repair + Immunotherapy = talazoparib + capecitabine +/- standard of care pembrolizumab Arm 1 Capecitabine Arm 1a: Patients who are ctDNA-positive and harbor a genomic target. DNA repair pathway = talazoparib + capecitabine (CLOSED) Arm 1b: Patients who are ctDNA-positive and harbor a genomic target. Immunotherapy pathway = pembrolizumab + capecitabine (CLOSED) Arm 1c: Patients who are ctDNA-positive and harbor a genomic target. PI3K Pathway = inavolisib + capecitabine ---\> +/- standard of care pembrolizumab Arm 1d: Patients who are ctDNA-positive and harbor a genomic target. DNA Repair + Immunotherapy = talazoparib + capecitabine +/- standard of care pembrolizumab Arm 2 Capecitabine Arm 2 subjects have plasma ctDNA positive but do not have a genomically driven treatment option. Treatment of physician's choice will be given with consideration for capecitabine and pembrolizumab. Dose, schedule and duration of treatment to be determined by treating physician. Arm 1 Pembrolizumab Arm 1a: Patients who are ctDNA-positive and harbor a genomic target. DNA repair pathway = talazoparib + capecitabine (CLOSED) Arm 1b: Patients who are ctDNA-positive and harbor a genomic target. Immunotherapy pathway = pembrolizumab + capecitabine (CLOSED) Arm 1c: Patients who are ctDNA-positive and harbor a genomic target. PI3K Pathway = inavolisib + capecitabine ---\> +/- standard of care pembrolizumab Arm 1d: Patients who are ctDNA-positive and harbor a genomic target. DNA Repair + Immunotherapy = talazoparib + capecitabine +/- standard of care pembrolizumab Arm 2 Pembrolizumab Arm 2 subjects have plasma ctDNA positive but do not have a genomically driven treatment option. Treatment of physician's choice will be given with consideration for capecitabine and pembrolizumab. Dose, schedule and duration of treatment to be determined by treating physician. Arm 3 Pembrolizumab Arm 3 subjects have plasma ctDNA negative. Treatment of patient and physician's choice will be given with consideration for capecitabine and pembrolizumab. Dose, schedule and duration of treatment to be determined by treating physician. Arm 1 Inavolisib Arm 1a: Patients who are ctDNA-positive and harbor a genomic target. DNA repair pathway = talazoparib + capecitabine (CLOSED) Arm 1b: Patients who are ctDNA-positive and harbor a genomic target. Immunotherapy pathway = pembrolizumab + capecitabine (CLOSED) Arm 1c: Patients who are ctDNA-positive and harbor a genomic target. PI3K Pathway = inavolisib + capecitabine ---\> +/- standard of care pembrolizumab Arm 1d: Patients who are ctDNA-positive and harbor a genomic target. DNA Repair + Immunotherapy = talazoparib + capecitabine +/- standard of care pembrolizumab
- Primary Outcome Measures
Name Time Method 2 year Disease Free Survival (DFS) ARM 1 2 year DFS is defined as the duration of time from arm assignment to time of a DFS event, defined as local failure (invasive), regional failure, distant failure, contralateral breast cancer (invasive or non-invasive), or death from any cause.
- Secondary Outcome Measures
Name Time Method Overall Disease Free Survival (DFS) 2 years Comparison of overall DFS in Arms 1, 2, 3; defined as the duration of time from arm assignment to time of a DFS event, defined as local failure (invasive), regional failure, distant failure, contralateral breast cancer (invasive or non-invasive), or death from any cause
2 year Disease Free Survival (DFS) in ARM 3 2 years DFS is defined as the duration of time from arm assignment to time of a DFS event, defined as local failure (invasive), regional failure, distant failure, contralateral breast cancer (invasive or non-invasive), or death from any cause.
Overall Distant Disease Free Survival (DDFS) 2 years DDFS is defined as the duration of time from arm assignment to time of recurrence of breast cancer outside the breast and/or death from any cause.
5 year Overall Survival (OS) 5 years Overall survival is defined as the time from date of treatment start until death from any cause.
Frequency and Severity of Adverse Events 1 year Adverse events will be assessed using CTCAE criteria v5
2 year Disease Free Survival (DFS) in ARM 2 2 years DFS is defined as the duration of time from arm assignment to time of a DFS event, defined as local failure (invasive), regional failure, distant failure, contralateral breast cancer (invasive or non-invasive), or death from any cause.
1 year Disease Free Survival (DFS) 1 year DFS is defined as the duration of time from arm assignment to time of a DFS event, defined as local failure (invasive), regional failure, distant failure, contralateral breast cancer (invasive or non-invasive), or death from any cause
Trial Locations
- Locations (13)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Georgetown University
🇺🇸Washington, District of Columbia, United States
Memorial Healthcare System
🇺🇸Hollywood, Florida, United States
Miami Cancer Institute at Baptist Health, Inc.
🇺🇸Miami, Florida, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
🇺🇸Indianapolis, Indiana, United States
Summit Health
🇺🇸Berkeley Heights, New Jersey, United States
Novant Health Cancer Institute
🇺🇸Winston-Salem, North Carolina, United States
Mays Cancer Center at UT Health San Antonio
🇺🇸San Antonio, Texas, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Froedtert and The Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Advocate Aurora Research Institute (Illinois)
🇺🇸Wauwatosa, Wisconsin, United States
Aurora Health Care
🇺🇸Wauwatosa, Wisconsin, United States