PARP Inhibition After Preoperative Chemotherapy in Patients With Triple Negative Breast Cancer or ER/PR +, HER2 Negative With Known BRCA1/2 Mutations: Hoosier Oncology Group BRE09-146
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.
Interventional
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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
No
Kathy D. Miller, M.D.
Study Chair
Hoosier Oncology Group
United States: Food and Drug Administration
BRE09-146
NCT01074970
February 2010
May 2014
Name | Location |
---|---|
University of Colorado Cancer Center | Denver, Colorado 80262 |
Virginia Oncology Associates | Newport News, Virginia 23606 |
Comprehensive Cancer Centers of Nevada | Las Vegas, Nevada 89109 |
Indiana University Melvin and Bren Simon Cancer Center | Indianapolis, Indiana 46202-5289 |
Hope A Women's Cancer Center | Asheville, North Carolina 28801 |
Siteman Cancer Center | Saint Louis, Missouri 63110 |
University of California Los Angeles | Los Angeles, California 90095-6951 |
Oregon Health Sciences University | Portland, Oregon |
The West Clinic | Memphis, Tennessee 38120 |
Northern Indiana Cancer Research Consortium | South Bend, Indiana |
The Center for Cancer & Hematologic Disease | Cherry Hill, New Jersey 08003 |
Central Coast Medical Oncology Corporation | Santa Maria, California 93454 |
Community Regional Cancer Center | Indianapolis, Indiana 46256 |
Fort Wayne Oncology & Hematology, Inc | Fort Wayne, Indiana 46815 |
University of Miami, Sylvester Comprehensive Cancer Center | Miami, Florida 33136 |
Presbyterian Medical Group | Albuquerque, New Mexico 87110 |
St. Jude Heritage Healthcare | Fullerton, California 92835 |
Monroe Medical Associates | Munster, Indiana 46321 |
Metro Health Cancer Care | Wyoming, Michigan 49519 |
University of New Mexico Cancer Care Alliance | Albuquerque, New Mexico 87131 |
Memorial Cancer Institute Breast Cancer Center | Hollywood, Florida 33021 |
Horizon Oncology Research, Inc./IU Health Arnett | Lafayette, Indiana 47905 |
Virtua Health Cancer Program | Mount Holly, New Jersey 08060 |
South Jersey Health Care | Vineland, New Jersey 08360 |
Seidman Cancer Center | Cleveland, Ohio 44106 |
Pinnacle Health Fox Chase Regional Cancer Center | Harrisburg, Pennsylvania 17110 |
Bux-Mont Oncology Hematology Associates (FCCC) at Grand View Hospital | Sellersville, Pennsylvania 18960 |