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

Official Title: “A Phase 2, Multi-Center, Single-Arm Study Evaluating Carboplatin/Gemcitabine in Combination With BSI-201 in Patients With Platinum-Sensitive Recurrent Ovarian Cancer”

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.

Intervention(s) in this Clinical Trial

• Drug: BSI-201
  • IV infusion, 5.6 mg/kg

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: BSI-201
  • BSI-201 in combination with gemcitabine and carboplatin.

Primary Measures

• To evaluate the objective response rate (ORR) of gemcitabine/carboplatin in combination with BSI-201
  • Time Frame: Until progressive disease or death
    Safety Issue?: No

Secondary Measures

• To determine the nature and degree of toxicity of gemcitabine/carboplatin in combination with BSI-201
  • Time Frame: 30 days after last BSI-201 exposure
    Safety Issue?: Yes
• To evaluate progression-free survival (PFS) of gemcitabine/carboplatin in combination with BSI-201
  • Time Frame: until progressive disease or death
    Safety Issue?: No

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:
• 1. Non-melanomatous skin cancer
• 2. In situ malignancies
• 3. Concurrent superficial endometrial carcinoma, if their endometrial carcinoma is superficial or invades less than 50% the thickness of the myometrium)
• 4. 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

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Sanofi-Aventis Industry

Overall Clinical Trial Officials and Contacts

Clinical Sciences & Operations Study Director Sanofi-Aventis  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01033123

Study ID Number: TCD11503

ClinicalTrials.gov Identifier: NCT01033123

Health Authority: United States: Food and Drug Administration