A Study Evaluating INIPARIB in Combination With Chemotherapy to Treat Triple Negative Breast Cancer Brain Metastasis

Study Overview
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Brief Summary
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The purpose of the study is to investigate the response rate for triple negative breast cancer patients with brain metastasis when INIPARIB is used in combination with irinotecan. Based on data generated by BiPar/Sanofi, it is concluded that iniparib does not possess characteristics typical of the PARP inhibitor class. The exact mechanism has not yet been fully elucidated, however based on experiments on tumor cells performed in the laboratory, iniparib is a novel investigational anti-cancer agent that induces gamma-H2AX (a marker of DNA damage) in tumor cell lines, induces cell cycle arrest in the G2/M phase in tumor cell lines, and potentiates the cell cycle effects of DNA damaging modalities in tumor cell lines. Investigations into potential targets of iniparib and its metabolites are ongoing.

Official Title
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A Phase II Study of the PARP Inhibitor, INIPARIB (BSI-201), in Combination With Chemotherapy to Treat Triple Negative Breast Cancer Brain Metastasis

Conditions
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Estrogen Receptor Negative (ER-Negative) Breast Cancer, Progesterone Receptor Negative (PR-Negative) Breast Cancer, Human Epidermal Growth Factor Receptor 2 Negative (HER2-Negative) Breast Cancer, Brain Metastases

Intervention / Treatment
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* Drug: INIPARIB + irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria - Histologically-confirmed, ER negative, PR negative and Her2 negative adenocarcinoma of the breast with brain lesion on radiographic imaging. ECOG Performance Status of 0-2. Life expectancy of >12 weeks. No limit to prior therapies with last anti-cancer treatment ≥ 2 weeks from initiation of protocol-based therapy provided all toxicities (other than alopecia) have resolved to ≤Grade 1 or baseline. No active serious infection or other comorbid illness which would impair ability to participate in the trial. Stable or decreasing dose of steroids for ≥ 7 days. Interval ≥ 4 weeks between open brain biopsy and initiation of protocol-based therapy. Patients must have adequate organ function. Exclusion Criteria - Pregnant or breast-feeding Prior allergic reaction to INIPARIB Prior allergic reaction to irinotecan. Evidence of hemorrhage or impending herniation on baseline brain imaging Evidence of diffuse leptomeningeal disease on brain MRI or by previously documented CSF cytology-NOTE: discrete dural metastases are permitted. Clinically significant cardiac, renal, hepatic, infectious or pulmonary disease which might affect trial participation. Concurrent or planned radiation, hormonal, chemotherapeutic, experimental or targeted biologic therapy. Contraindication to gadolinium-enhanced MRI imaging. Inability to comply with study and/or follow-up procedures.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INIPARIB, irinotecan<br> | Drug: INIPARIB + irinotecan<br>* 21 day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy | AS measured by intra or extra cranial time to progression (TTP) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | as measured by RECIST | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Triple negative breast cancer, Brain metastasis, BSI-201, iniparib