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

Breast Cancer Clinical Trial

Official title: 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

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Triple Negative Breast Neoplasms

• NCT number: NCT01074970
• Study type: Interventional
• Source: Hoosier Cancer Research Network
• Status: Completed
• Phase: Phase 2
• Start date: February 2010
• Completion date: December 15, 2018