Circulating Tumor DNA Enriched, Genomically Directed Post-neoadjuvant Trial for Patients With Residual Triple Negative Breast Cancer

NCT04849364 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: HCRN BRE18-334
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 13

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).

Conditions

Breast Cancer; Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• ARM 1c: Disease Free Survival (DFS) at 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.

  2 years

Secondary Outcomes (7)

• ARM 2: Disease Free Survival (DFS) at 2 Years

  2 years

• ARM 3:Disease Free Survival (DFS) at 2 Years

  2 years

• Overall Disease Free Survival (DFS)

  Up to 29 months

• Overall Distant Disease Free Survival (DDFS)

  Up to 29 months

• 1-year Disease Free Survival (DFS)

  1 year

Study Arms (3)

Arm 1

EXPERIMENTAL

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

Drug: Capecitabine; Drug: Talazoparib; Drug: Pembrolizumab; Drug: Inavolisib

Arm 2

ACTIVE COMPARATOR

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.

Drug: Capecitabine; Drug: Pembrolizumab

Arm 3

ACTIVE COMPARATOR

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.

Drug: Capecitabine; Drug: Pembrolizumab

Interventions

Capecitabine DRUG

Capecitabine 1000 mg/m2 BID Orally 14 days on and 7 days off Cycle = 21 days; Total of 8 cycles

Also known as: Xeloda

Arm 1; Arm 2; Arm 3

Talazoparib DRUG

Talazoparib Cycle 1: 0.75 mg then Cycle 2-8: 1 mg Cycle = 21 days; Total of 8 cycles

Also known as: Talzenna

Arm 1

Pembrolizumab DRUG

Per standard of care.

Also known as: Keytruda

Arm 1; Arm 2; Arm 3

Inavolisib DRUG

Inavolisib Cycle 1: 6 mg then Cycle 2-8: 9mg Orally 21 days on Cycle = 21 days; Total of 8 cycles

Also known as: GDC-0077

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or may be obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status 0 or 1 within 28 days prior to study registration.
• Must have histologically or cytologically confirmed triple negative (ER-/PR-/HER2-) invasive breast cancer per pathology report. NOTE: ER and PR will be considered negative if ≤ 10% of cells stain weakly positive. HER2 will be considered negative if scored 0 or 1+ by immunohistochemistry (IHC) or 2+ by IHC associated with a fluorescence in situ hybridization (FISH) ratio of \< 2.0 or \< 6 copies per cell.
• Must have clinical stage I-III at diagnosis (AJCC 8th edition) based on initial evaluation by physical examination and/or breast imaging prior to neoadjuvant chemotherapy.
• Must have completed preoperative (neoadjuvant) chemotherapy for this index case. NOTE: Acceptable preoperative regimens include an anthracycline or a taxane, or both. Participants who received preoperative therapy as part of a clinical trial may enroll. Participants may not have received adjuvant chemotherapy after surgery prior to registration. Bisphosphonate use is allowed.
• Subjects who received pembrolizumab in the neoadjuvant setting are eligible and may continue treatment during the screening process. Subjects assigned to Arm 1 will require a 3 week wash out period prior to initiation of study treatment. Subjects may resume pembrolizumab to complete the planned year of therapy (17 cycles) after completion of study therapy based on investigator discretion. Subjects assigned to Arm 2 and Arm 3 may continue pembrolizumab treatment during the study based on investigator discretion. Total duration of pembrolizumab treatment should not be extended beyond 17 cycles.
• Must have significant residual invasive disease at the time of definitive surgery following preoperative chemotherapy. Significant residual disease is defined as at least one of the following:
• Residual invasive disease in the breast measuring at least 1 cm. The presence of DCIS without invasion does not qualify as residual disease in the breast.
• Any macroscopic, (≥ 2mm) residual, lymph node involvement regardless of primary tumor site involvement (includes no residual disease in the breast).
• Residual cancer burden (RCB) score 2 or 3.
• Must have completed definitive resection of primary tumor. Participants must begin assigned arm therapy no later than 96 days from the last local therapy. NOTE: Negative margins for both invasive and ductal carcinoma in situ (DCIS) are desirable, however participants with positive margins may enroll if the study site treatment team believes no further surgery is possible and participant has received radiotherapy. Participants with margins positive for lobular carcinoma in situ (LCIS) are eligible. Either mastectomy or breast conserving surgery (including lumpectomy or partial mastectomy) is acceptable.
• Breast Radiotherapy
• Radiotherapy is required for participants who underwent breast-conserving therapy, including lumpectomy or partial mastectomy unless deemed inappropriate by the treating provider.
• Post mastectomy radiation is at the discretion of the treating physician.

You may not qualify if:

• Clinically significant infections as judged by the treating physician.
• Stage IV (metastatic) disease, however no specific staging studies are required in the absence of symptoms or physical exam findings that would suggest distant disease.
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial. NOTE: Patients without a known history of being HIV positive do not require testing at screening. Patients who are known to be HIV positive will require testing as described to be eligible for this trial. Testing should be considered standard of care.
• Patients with evidence of chronic hepatitis B virus (HBV) infection, with undetectable HBV viral load within 6 months of registration are eligible for this trial. They should be on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, the HCV viral load must be undetectable within 6 months of registration to be eligible for this trial. NOTE: Patients without a known history of being hepatitis positive do not require testing at screening. Patients who are known to be hepatitis positive will require testing as described to be eligible for this trial. Testing should be considered standard of care.
• Participants with unstable angina or a myocardial infarction within 12 months of study registration.
• Active second malignancy (except non-melanomatous skin cancer or incidental prostate cancer found on cystectomy): Active second malignancy is defined as a current need for cancer therapy or a high possibility (\> 30%) of recurrence during the study. Previous contralateral breast cancer is allowable unless it meets "active" criteria as stated above.
• Inability to swallow pills.
• Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol, safety of participation, or interpretation of results. This includes significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome) or any other serious medical condition or abnormality in clinical laboratory tests that meet these criteria in the investigator's opinion.
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to any of the study medications being used in this study.
• Treatment with any investigational agent within 30 days prior to study registration.
• Any concurrent ocular or intraocular condition (e.g., cataract or diabetic retinopathy) that, in the opinion of the investigator, would require medical or surgical intervention during the study period to prevent or treat vision loss that might result from that condition.
• Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes.
• Active inflammatory (e.g., uveitis or vitritis) or infectious (e.g., conjunctivitis, keratitis, scleritis, or endophthalmitis) conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye.
• Symptomatic active lung disease, including pneumonitis
• History of or active inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis). Patients currently receiving immunosuppressants for inflammatory bowel disease (e.g., sulfasalazine) are considered to have active disease and are therefore ineligible.

Sponsors & Collaborators

• Bryan Schneider, MD: lead
• Genentech, Inc.: collaborator
• Pfizer: collaborator
• Foundation Medicine: collaborator
• Indiana University: collaborator
• Vera Bradley Foundation for Breast Cancer: collaborator

Study Sites (13)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20057, United States

Location

Memorial Healthcare System

Hollywood, Florida, 33028, United States

Location

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, 33176, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Summit Health

Berkeley Heights, New Jersey, 07922, United States

Location

Novant Health Cancer Institute

Winston-Salem, North Carolina, 27103, United States

Location

Mays Cancer Center at UT Health San Antonio

San Antonio, Texas, 78229, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

Froedtert and The Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Advocate Aurora Research Institute (Illinois)

Wauwatosa, Wisconsin, 53226, United States

Location

Aurora Health Care

Wauwatosa, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Capecitabine; talazoparib; pembrolizumab; inavolisib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Fauzia Sharmin
• Organization: Hoosier Cancer Research Network

fsharmin@hoosiercancer.org

317-921-2050

Study Officials

• Bryan P Schneider, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: April 13, 2021
• First Posted: April 19, 2021
• Study Start: August 24, 2021
• Primary Completion: October 24, 2024
• Study Completion: December 2, 2024
• Last Updated: May 31, 2025
• Results First Posted: May 31, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)