Randomized Controlled Trial of Genomically Directed Therapy in Patients With Triple Negative Breast Cancer

NCT02101385 | Completed Phase 2 Results DMC

• 1 other identifier: BRE12-158
• Study Type: interventional
• Target: 193
• Locations: 1 country
• Sites: 29

Brief Summary

This study will test the theory that therapy designed for each individual's tumor will improve outcomes over standard of care in a population that needs a better standard.

Conditions

Malignant Neoplasm of Breast; Breast Cancer

Keywords

Genomically-Directed Therapy; DNA Sequencing; RNA Sequencing

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Two-Year Disease-Free Survival (DFS)

  Two-year disease-free survival (DFS) in participants with confirmed triple negative breast cancer (TNBC) treated with a genomically directed therapy or standard of care following preoperative chemotherapy. The survival probabilities for arm A and arm B were estimated as 2 year disease free survival. DFS is defined as the duration of time from randomization 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.

  From C1D1 until death or up to a maximum of 24 months.

Secondary Outcomes (4)

• Comparison Between Overall Disease-Free Survival

  From C1D1 until death or up to a maximum of 58 months

• Comparison Between One Year Disease Free Survival

  From C1D1 until death or up to a maximum of 12 months

• Five-Year Overall Survival (OS) Rate

  From C1D1 until death or up to a maximum of 60 months

• Number of Patients With Adverse Events as a Measure of Safety and Tolerability

  From C1D1 until death or up to a maximum of 60 months

Study Arms (2)

Arm A (Genomically Directed Monotherapy)

EXPERIMENTAL

Participants randomized to Experimental Arm A will receive an FDA approved drug at standard dose for four cycles (12-16 weeks total duration, depending on cycle length). Clinical and laboratory monitoring and dose-reductions will follow the FDA package insert guidelines.

Drug: Genomically Directed Monotherapy

Control Arm B (Observation/Standard Therapy)

OTHER

Currently no standard therapy has proven efficacy in this patient population and thus observation alone would be considered standard of care. Additional therapy is permitted, however, if deemed appropriate by the treating physician.

Other: Observation/Standard Therapy

Interventions

Genomically Directed Monotherapy DRUG

Participants randomized to Experimental Arm A will receive an FDA approved drug at standard dose for four cycles (12-16 weeks total duration, depending on cycle length). The CGTB will assign therapy to each participant individually based on biomarkers/pathways identified by DNA sequencing:

Arm A (Genomically Directed Monotherapy)

Observation/Standard Therapy OTHER

Currently no standard therapy has proven efficacy in this patient population and thus observation alone would be considered standard of care. Additional therapy is permitted, however, if deemed appropriate by the treating physician.

Control Arm B (Observation/Standard Therapy)

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.
• NOTE: Central pathology review may be conducted any time after definitive surgery. Consenting participants may be pre-registered to the study and proceed with central pathology review before full eligibility has been confirmed. However, ALL of the eligibility criteria must be met and formal study registration completed prior to submission of the sample for sequencing.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status 0 or 1 within 14 days prior to study registration.
• Women and men of childbearing potential must be willing to use an effective method of contraception (e.g. hormonal or barrier method of birth control; abstinence) from the time consent is signed until 4 weeks after protocol therapy discontinuation.
• Women of childbearing potential must have a negative pregnancy test within 30 days prior to study registration. Women should be counseled regarding acceptable birth control methods to utilize from the time of screening to start of treatment. If prior to treatment after discussion with the subject it is felt by the treating physician there is a possibility the subject is pregnant a pregnancy test should be repeated.
• NOTE: Women are considered not of childbearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), or they are postmenopausal for at least 12 consecutive months.
• Women must not be breastfeeding.
• Must have histologically or cytologically confirmed triple negative (ER-/PR-/HER2-) invasive breast cancer, clinical stage I-III at diagnosis (AJCC 6th edition) based on initial evaluation by physical examination and/or breast imaging prior to study registration. NOTE: ER, PR and HER2 status will be confirmed by central pathology review prior to randomization. ER and PR will be considered negative if ≤ 1% 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 completed preoperative (neoadjuvant) chemotherapy. 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 randomization. Bisphosphonate use is allowed.
• Must have completed definitive resection of primary tumor. The most recent surgery for breast cancer must have been completed at least 14 days prior (but no more than 84 days prior) to study registration. NOTE: Negative margins for both invasive and ductal carcinoma in situ (DCIS) are desirable, however participants with positive margins may enroll if the treatment team believes no further surgery is possible and patient 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.
• 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 Cancer Burden (RBC) classification II or III\^6
• Residual invasive disease in the breast measuring at least 2 cm. The presence of DCIS without invasion does not qualify as residual disease in the breast.

You may not qualify if:

• No 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.
• No treatment with any investigational agent within 30 days prior to study registration.
• No history of chronic hepatitis B or or untreated hepatitis C.
• No clinically significant infections as judged by the treating physician.
• No 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.

Sponsors & Collaborators

• Bryan Schneider, MD: lead
• Hoosier Cancer Research Network: collaborator
• Vera Bradley Foundation for Breast Cancer: collaborator
• Walther Cancer Institute: collaborator
• Indiana University: collaborator

Study Sites (29)

University of Alabama Hematology Oncology Clinic at Medical West

Birmingham, Alabama, 35294, United States

Location

Georgetown University: Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

University of Florida: Shands Cancer Center

Gainesville, Florida, 32610, United States

Location

Memorial Cancer Institute

Hollywood, Florida, 33021, United States

Location

University of Miami, Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Memorial Breast Cancer Center: Memorial West

Pembroke Pines, Florida, 33028, United States

Location

Emory University: Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

Community Hospital of Anderson and Madison County, Inc

Anderson, Indiana, 46011, United States

Location

Fort Wayne Oncology & Hematology, Inc.

Fort Wayne, Indiana, 46845, United States

Location

IU Health Goshen Hospital

Goshen, Indiana, 46527, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Community Regional Cancer Center

Indianapolis, Indiana, 46256, United States

Location

St. Vincent Hospital

Indianapolis, Indiana, 46260, United States

Location

IU Health Arnett Cancer Center

Lafayette, Indiana, 47904, United States

Location

Community Healthcare System: Monroe Medical Associates

Munster, Indiana, 46321, United States

Location

Northern Indiana Cancer Research Consortium

South Bend, Indiana, 46628, United States

Location

Meritus Center for Clinical Research

Hagerstown, Maryland, 21742, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Washington University: Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68114, United States

Location

University of Cincinnati Cancer Institute

Cincinnati, Ohio, 45267, United States

Location

Mercy Clinic Oncology & Hematology: McAuley

Oklahoma City, Oklahoma, 73120, United States

Location

Pinnacle Health Cancer Center

Harrisburg, Pennsylvania, 17109, United States

Location

Erlanger Health System

Chattanooga, Tennessee, 37403, United States

Location

Joe Arrington Cancer Research and Treatment Center

Lubbock, Texas, 79410, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Froedtert/Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Aurora Health Care

Wauwatosa, Wisconsin, 53226, United States

Location

Related Publications (2)

• Schneider BP, Jiang G, Ballinger TJ, Shen F, Chitambar C, Nanda R, Falkson C, Lynce FC, Gallagher C, Isaacs C, Blaya M, Paplomata E, Walling R, Daily K, Mahtani R, Thompson MA, Graham R, Cooper ME, Pavlick DC, Albacker LA, Gregg J, Solzak JP, Chen YH, Bales CL, Cantor E, Hancock BA, Kassem N, Helft P, O'Neil B, Storniolo AMV, Badve S, Miller KD, Radovich M. BRE12-158: A Postneoadjuvant, Randomized Phase II Trial of Personalized Therapy Versus Treatment of Physician's Choice for Patients With Residual Triple-Negative Breast Cancer. J Clin Oncol. 2022 Feb 1;40(4):345-355. doi: 10.1200/JCO.21.01657. Epub 2021 Dec 15.

  PMID: 34910554 DERIVED

• Radovich M, Jiang G, Hancock BA, Chitambar C, Nanda R, Falkson C, Lynce FC, Gallagher C, Isaacs C, Blaya M, Paplomata E, Walling R, Daily K, Mahtani R, Thompson MA, Graham R, Cooper ME, Pavlick DC, Albacker LA, Gregg J, Solzak JP, Chen YH, Bales CL, Cantor E, Shen F, Storniolo AMV, Badve S, Ballinger TJ, Chang CL, Zhong Y, Savran C, Miller KD, Schneider BP. Association of Circulating Tumor DNA and Circulating Tumor Cells After Neoadjuvant Chemotherapy With Disease Recurrence in Patients With Triple-Negative Breast Cancer: Preplanned Secondary Analysis of the BRE12-158 Randomized Clinical Trial. JAMA Oncol. 2020 Sep 1;6(9):1410-1415. doi: 10.1001/jamaoncol.2020.2295.

  PMID: 32644110 DERIVED

Related Links

• Hoosier Cancer Research Network Website

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Observation; Standard of Care

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Annesha Majumdar
• Organization: Hoosier Cancer Research Network

amajumdar@hoosiercancer.org

3179212050

Study Officials

• Bryan Schneider, M.D.

  Hoosier Cancer Research Network

  STUDY CHAIR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: March 21, 2014
• First Posted: April 2, 2014
• Study Start: April 3, 2014
• Primary Completion: February 21, 2021
• Study Completion: September 9, 2022
• Last Updated: September 28, 2023
• Results First Posted: September 28, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (29)