A Single-Arm Study Evaluating Carboplatin/Gemcitabine in Combination With BSI-201 in Patients With Platinum-Sensitive Recurrent Ovarian Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of BSI-201 on the objective response rate in platinum-sensitive recurrent ovarian cancer patients receiving gemcitabine and carboplatin. 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 2, Multi-Center, Single-Arm Study Evaluating Carboplatin/Gemcitabine in Combination With BSI-201 in Patients With Platinum-Sensitive Recurrent Ovarian Cancer

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: BSI-201


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years of age Histological diagnosis of epithelial ovarian carcinoma, fallopian tube cancer, or primary peritoneal carcinoma Completion of only one previous course of chemotherapy which contained a platinum therapy, with sensitivity to that regimen. Platinum-sensitivity is defined by a relapse greater than 6 months after termination of platinum-based chemotherapy Measurable disease, defined by at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded), and is ≥ 20 mm when measured by conventional techniques (palpation, plain x-ray, computed tomography [CT], or magnetic resonance imaging [MRI]) or ≥ 10 mm when measured by spiral CT Adequate organ function defined as: absolute neutrophil count (ANC) ≥ 1,500/mm3, platelets ≥ 100,000/mm3, creatinine clearance > 50mL/min, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN; or < 5 x ULN in case of liver metastases); total bilirubin < 1.5 mg/dL For women of child bearing potential, documented negative pregnancy test within two weeks of study entry and agreement to acceptable birth control during the duration of the study therapy Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 Signed, institutional review board (IRB) approved written informed consent Exclusion Criteria: Concurrent invasive malignancy, not including: Non-melanomatous skin cancer In situ malignancies Concurrent superficial endometrial carcinoma, if their endometrial carcinoma is superficial or invades less than 50% the thickness of the myometrium) Low risk breast cancer (localized, non-inflammatory) treated with curative intent Lesions identifiable only by positron emission tomography (PET) Prior treatment with poly (ADP-ribose) polymerase (PARP) inhibitors, including BSI-201 Major medical conditions that might affect study participation (i.e., uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection) Other significant co-morbid condition which the investigator feels might compromise effective and safe participation in the study, including a history of congestive cardiac failure or an electrocardiogram (ECG) suggesting significant conduction defect or myocardial ischemia Enrollment in another investigational device or drug study, or current treatment with other investigational agents Concurrent radiation therapy to treat primary disease throughout the course of the study Inability to comply with the requirements of the study Pregnancy or lactation Leptomeningeal disease or brain metastases requiring steroids or other therapeutic intervention

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: BSI-201<br>BSI-201 in combination with gemcitabine and carboplatin. | Drug: BSI-201<br>* IV infusion, 5.6 mg/kg<br>* Other names: PARP inhibitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the objective response rate (ORR) of gemcitabine/carboplatin in combination with BSI-201 |  | Until progressive disease or death | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the nature and degree of toxicity of gemcitabine/carboplatin in combination with BSI-201 |  | 30 days after last BSI-201 exposure | 
| To evaluate progression-free survival (PFS) of gemcitabine/carboplatin in combination with BSI-201 |  | until progressive disease or death | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ovarian, cancer, sensitive, PARP, recurrent, platinum-sensitive recurrent ovarian cancer