Clinical trial NCT01033123: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: ovarian
cancer
sensitive
PARP
recurrent
platinum-sensitive recurrent ovarian cancer
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2009-12-16
Enrollment: 41
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: To evaluate the objective response rate (ORR) of gemcitabine/carboplatin in combination with BSI-201
timeFrame: Until progressive disease or death
Secondary outcomes:
measure: To determine the nature and degree of toxicity of gemcitabine/carboplatin in combination with BSI-201
timeFrame: 30 days after last BSI-201 exposure
measure: To evaluate progression-free survival (PFS) of gemcitabine/carboplatin in combination with BSI-201
timeFrame: until progressive disease or death
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts Ceneral Hospital
state: Massachusetts
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: