PARP Inhibition for Triple Negative Breast Cancer (ER-/PR-/HER2-)With BRCA1/2 Mutations

NCT01074970 | Completed Phase 2 Results DMC

• 1 other identifier: BRE09-146
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 27

Brief Summary

The purpose of this trial is to evaluate 2-year disease-free survival in this patient population treated with single agent cisplatin and patients treated with cisplatin in combination with Rucaparib following preoperative chemotherapy. Side effects and tolerability of this treatment in patients with residual disease following preoperative chemotherapy will also be observed and characterized.

Conditions

Breast Cancer

Keywords

PARP inhibition + breast cancer; breast cancer; PARP inhibitor; Triple negative

Outcome Measures

Primary Outcomes (1)

• Two-year Disease Free Survival

  To evaluate 2-year disease-free survival (DFS), in patients with confirmed TNBC or ER/PR + HER2-, known BRCA1/2 mutations treated with single agent cisplatin and patients treated with cisplatin in combination with Rucaparib following preoperative chemotherapy

  24 months

Secondary Outcomes (3)

• Five-year Disease Free Survival

  60 months

• Overall Survival

  60 months

• Summarize Grade 2,3, # 4 Toxicities

  12 months

Study Arms (2)

Arm A: Cisplatin Monotherapy

ACTIVE COMPARATOR

Cisplatin 75 mg/m2 IV infusion over 60 minutes, D1 every 21 days for 4 cycles

Drug: Cisplatin

Arm B: Combination Therapy

ACTIVE COMPARATOR

Rucaparib 24mg C1,30mg C2-4, D1,2,3 every 21 days for 4 cycles Cisplatin 75 mg/m2 IV infusion over 60 minutes, D1 every 21 days for 4 cycles

Drug: Rucaparib; Drug: Cisplatin

Interventions

Cisplatin DRUG

Cisplatin 75 mg/m2 IV infusion over 60 minutes, D1 every 21 days for 4 cycles

Arm A: Cisplatin Monotherapy

Rucaparib DRUG

Rucaparib 24mg C1,30mg C2-4, D1,2,3 every 21 days for 4 cycles

Arm B: Combination Therapy

Eligibility Criteria

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

You may qualify if:

• Must have histologically or cytologically confirmed triple negative (ER-/PR-/HER2-) invasive breast cancer, stage I-III at diagnosis (AJCC 6th edition) based on initial evaluation by clinical examination and/or breast imaging. NOTE: Patients with ER+ and/or PR+ may enroll ONLY if they are known carriers of a deleterious mutation in BRCA1 or BRCA2. Patients with HER2+ tumors may not enroll regardless of BRCA status.
• Must have completed preoperative (neoadjuvant) chemotherapy. NOTE: Acceptable preoperative regimens include an anthracycline or a taxane, or both. Patients may NOT have received cisplatin as part of their neoadjuvant therapy regimen. Patients who received preoperative therapy as part of a clinical trial may enroll. No adjuvant chemotherapy after surgery other than that specified in this protocol is allowed. Adjuvant bisphosphonate use is allowed.
• Must have completed definitive resection of primary tumor. The last surgery for breast cancer must have been completed at least 14 days prior to registration for protocol therapy.
• Must have significant residual invasive disease at the time of definitive surgery following preoperative chemotherapy. Significant residual disease is defined at least one of the following:
• Miller-Payne response in the breast of 0-25.
• Residual Cancer Burden (RBC) classification II or III6
• Residual carcinoma in one or more regional lymph nodes that would meet AJCC 6th edition criteria for N1 - N3 disease.
• Alternatively, if Miller-Payne or RCB grading is not available, the patient will be eligible if the pathology report indicates that the area of residual invasive disease in the breast measures at least 2 cm following preoperative therapy. The presence of DCIS without invasion does not qualify as residual disease in the breast.
• Whole breast radiotherapy is required for patients who underwent breast conserving therapy, including lumpectomy or partial mastectomy. Patients receiving adjuvant radiation therapy must have completed radiotherapy at least 14 days prior to registration for protocol therapy.
• Written informed consent and HIPAA authorization for release of personal health information.
• Age \> 18 years at the time of consent.
• Must consent to allow submission of archived tumor tissue sample from definitive surgery.
• Must consent to collection of blood samples for PK analysis.
• Women of childbearing potential and males must be willing to use an effective method of contraception from the time consent is signed until 4 weeks after treatment discontinuation.
• Women of childbearing potential must have a negative pregnancy test within 14 days prior to registration for protocol therapy.

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 registration for protocol therapy.
• No history of chronic hepatitis B or C
• No clinically significant infections as judged by the treating investigator.

Sponsors & Collaborators

• Hoosier Cancer Research Network: lead
• Clovis Oncology, Inc.: collaborator

Study Sites (27)

St. Jude Heritage Healthcare

Fullerton, California, 92835, United States

Location

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

Central Coast Medical Oncology Corporation

Santa Maria, California, 93454, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Memorial Cancer Institute Breast Cancer Center

Hollywood, Florida, 33021, United States

Location

University of Miami, Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Fort Wayne Oncology & Hematology, Inc

Fort Wayne, Indiana, 46815, 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

Horizon Oncology Research, Inc./IU Health Arnett

Lafayette, Indiana, 47905, United States

Location

Monroe Medical Associates

Munster, Indiana, 46321, United States

Location

Northern Indiana Cancer Research Consortium

South Bend, Indiana, 46601, United States

Location

Metro Health Cancer Care

Wyoming, Michigan, 49519, United States

Location

Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89128, United States

Location

The Center for Cancer & Hematologic Disease

Cherry Hill, New Jersey, 08003, United States

Location

Virtua Health Cancer Program

Mount Holly, New Jersey, 08060, United States

Location

South Jersey Health Care

Vineland, New Jersey, 08360, United States

Location

Presbyterian Medical Group

Albuquerque, New Mexico, 87110, United States

Location

University of New Mexico Cancer Center: Albuquerque

Albuquerque, New Mexico, 87131, United States

Location

HOPE a Women's Cancer Center

Asheville, North Carolina, 28806, United States

Location

Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

Pinnacle Health Fox Chase Regional Cancer Center

Harrisburg, Pennsylvania, 17110, United States

Location

Bux-Mont Oncology Hematology Associates (FCCC) at Grand View Hospital

Sellersville, Pennsylvania, 18960, United States

Location

The West Clinic

Memphis, Tennessee, 38138, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Related Publications (3)

• S. R. Malireddy, S. M. Perkins, S. S. Badve, G. W. Sledge, K. Miller. PARP inhibition after preoperative chemotherapy in patients with triple negative breast cancer (TNBC) or known BRCA1/2 mutations: Hoosier oncology group BRE09-146. J Clin Oncol 29: 2011 (suppl; abstr TPS130)

  BACKGROUND

• S. Dwadasi, Y. Tong, T. Walsh, M.A. Danso, C.X. Ma, P.A Silverman, M.C. King, S.M. Perkins, S.S. Badve, K. Miller. Cisplatin with or without rucaparib after preoperative chemotherapy in patients with triple negative breast cancer: Hoosier Oncology Group BRE09-146. J Clin Oncol 32:5s, 2014 (suppl; abstr 1019^)

  BACKGROUND

• Miller K, Tong Y, Jones DR, Walsh T, Danso MA, Ma CX, Silverman P, King MC, Badve SS, Perkins SM. Cisplatin with or without rucaparib after preoperative chemotherapy in patients with triple negative breast cancer: Final efficacy results of Hoosier Oncology Group BRE09-146. J Clin Oncol 33:5s, 2015 (suppl; abstr 1082)

  RESULT

Related Links

• Hoosier Cancer Research Network Homepage

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cisplatin; rucaparib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Director of Clinical Data Management
• Organization: Hoosier Cancer Research Network

jsmith@hoosiercancer.org

317-634-5842

Study Officials

• Kathy D. Miller, 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: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2010
• First Posted: February 24, 2010
• Study Start: February 1, 2010
• Primary Completion: December 15, 2018
• Study Completion: December 15, 2018
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-09

Locations

US (27)