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

NCT ID: NCT01074970

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 135 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-02-28
• Study Completion Date: 2018-12-15

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.

Detailed Description

OUTLINE: This is a multi-center study.

Safety Run-in will be for the first 12 patients on study only (6 in cohort 1 and 6 in cohort 2). Patients in the safety run will be included in the efficacy analysis on intent to treat basis:

Cisplatin 75 mg/m2 IV D1 every 3 weeks x 4 cycles; Rucaparib 16-30 mg IV D 1,2,3 every 3 weeks x 4 cycles

If cycle 1 is well tolerated, the dose of Rucaparib will be escalated from 16 mg to 24 mg for subsequent cycles in the cohort 1, and 24 mg to 30 mg in the cohort 2.

If ≤ 1 of 6 patients in cohort 1 experiences DLT, cohort 2 will commence. If 2 or more of 6 patients in cohort 1 experience DLT, the study will be suspended and an amendment to explore lower doses will be considered.

If ≤ 1 of 6 patients in cohort 2 experiences DLT, the randomized portion of the study will commence. If 2 or more of 6 patients experience DLT, the study will be suspended and an amendment to proceed with the randomized portion at the cohort 2 dose (24 mg) will be considered.

During the randomized portion of the study, patients will be randomized to either Arm A or Arm B.

Stratification factors:

• Anthracycline vs. not
• Residual LN involvement vs. No Residual LN involvement

Arm A (Cisplatin Monotherapy) Cisplatin 75 mg/m2 IV D1 every 3 weeks x 4 cycles

Arm B (Combination Therapy) Cisplatin 75 mg/m2 IV D1 every 3 weeks x 4 cycles; Rucaparib 16-30 mg IV D1,2,3 every 3 weeks x 4 cycles

Rucaparib maintenance 30 mg IV weekly x 24 weeks

ECOG Performance Status 0-1

Life Expectancy: Not Specified

Hematopoietic:

• Hemoglobin (Hgb) > 9.0 g/dL
• Platelets > 100 K/ mm3
• Absolute neutrophil count (ANC) > 1.5 K/mm3

Hepatic:

• Bilirubin < upper limit of normal (except in patients with documented Gilbert's disease, who must have a total bilirubin < 3.0 mg/dL)
• Aspartate aminotransferase (AST, SGOT) < 2.5 x ULN
• Alanine aminotransferase (ALT, SGPT) < 2.5 x ULN

Renal:

• Calculated creatinine clearance of > 50 cc/min using the Cockcroft-Gault formula

Cardiovascular:

• Left ventricular ejection fraction within normal limits.
• Patients with an unstable angina or myocardial infarction within 12 months of study entry are excluded.
• No clinically significant arrhythmia or baseline ECG abnormalities in the opinion of the treating investigator.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: Cisplatin Monotherapy

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

Group Type: ACTIVE_COMPARATOR

Cisplatin

Intervention Type: DRUG

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

Arm B: Combination Therapy

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

Group Type: ACTIVE_COMPARATOR

Rucaparib

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

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

Interventions

Cisplatin

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

Intervention Type: DRUG

Rucaparib

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

Intervention Type: DRUG

Cisplatin

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.
• Women must not be breastfeeding.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clovis Oncology, Inc.

INDUSTRY

Sponsor Role: collaborator

Hoosier Cancer Research Network

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kathy D. Miller, M.D.

Role: STUDY_CHAIR

Hoosier Cancer Research Network

Locations

St. Jude Heritage Healthcare

Fullerton, California, United States

University of California Los Angeles

Los Angeles, California, United States

Central Coast Medical Oncology Corporation

Santa Maria, California, United States

University of Colorado Cancer Center

Aurora, Colorado, United States

Memorial Cancer Institute Breast Cancer Center

Hollywood, Florida, United States

University of Miami, Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Fort Wayne Oncology & Hematology, Inc

Fort Wayne, Indiana, United States

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Community Regional Cancer Center

Indianapolis, Indiana, United States

Horizon Oncology Research, Inc./IU Health Arnett

Lafayette, Indiana, United States

Monroe Medical Associates

Munster, Indiana, United States

Northern Indiana Cancer Research Consortium

South Bend, Indiana, United States

Metro Health Cancer Care

Wyoming, Michigan, United States

Siteman Cancer Center

St Louis, Missouri, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

The Center for Cancer & Hematologic Disease

Cherry Hill, New Jersey, United States

Virtua Health Cancer Program

Mount Holly, New Jersey, United States

South Jersey Health Care

Vineland, New Jersey, United States

Presbyterian Medical Group

Albuquerque, New Mexico, United States

University of New Mexico Cancer Center: Albuquerque

Albuquerque, New Mexico, United States

HOPE a Women's Cancer Center

Asheville, North Carolina, United States

Seidman Cancer Center

Cleveland, Ohio, United States

Oregon Health Sciences University

Portland, Oregon, United States

Pinnacle Health Fox Chase Regional Cancer Center

Harrisburg, Pennsylvania, United States

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

Sellersville, Pennsylvania, United States

The West Clinic

Memphis, Tennessee, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

Countries

United States

References

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)

Reference Type: 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^)

Reference Type: 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)

Reference Type: RESULT

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.hoosiercancer.org

Hoosier Cancer Research Network Homepage

Other Identifiers

BRE09-146

Identifier Type: -

Identifier Source: org_study_id