A Study of ABT-263 as Single Agent in Women With Platinum Resistant/Refractory Recurrent Ovarian Cancer

Study Overview
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Brief Summary
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ABT-263 as single agent in women with platinum resistant/refractory recurrent ovarian cancer.

Official Title
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A Study of ABT-263 as Single Agent in Women With Platinum Resistant/Refractory Recurrent Ovarian Cancer

Conditions
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Platinum-resistant or Refractory Ovarian Cancer

Intervention / Treatment
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* Drug: ABT-263


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Woman older than 18 years Subjects with Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 Histologically and/or cytologically documented high grade serous epithelial cancer of ovarian, fallopian tube or peritoneum Platinum resistant ovarian cancer defined as relapsing within 6 months after a platinum based chemotherapy OR platinum refractory ovarian cancer defined as progressing during a platinum based chemotherapy (excepted refractory patients in first line) Subjects having received at least 2 prior lines of treatments including platinum regimen Subjects who are willing and able to comply with the protocol and study procedures including willingness to undergo tumor biopsy before therapy at screening There is no limitation to prior number of therapies Patients must have documented disease progression Subjects who have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Adequate bone marrow, renal and hepatic function per local laboratory reference range as follows:• Absolute Neutrophil Count ≥ 1500/ mm3 Platelets ≥ 150,000 / mm3 Hemoglobin ≥ 9.0 g/dL Renal function: Serum creatinine ≤1.2mg/dL or calculated creatinine clearance ≥ 60mL/min AST/ALT ≤ 3.0× the upper limit of normal (ULN); [Subjects with liver metastasis may have AST, ALP, and ALT less then or equal to 5.0 X ULN] Bilirubin ≤ 1.25×ULN Coagulation: aPTT and PT not to exceed 1.2 × ULN LVEF > 50% by echocardiograms or MUGA Patients must give written informed consent Exclusion Criteria: Patient's refusal or impossibility to perform biopsy on relapsing disease Bowel occlusive syndrome or other gastro-intestinal disorder that does not allow oral medication such as malabsorption Patients with platinum refractory disease in first line Received radio-immunotherapy within 6 months of 1st dose of study drug Received steroid therapy for anti-neoplastic intent within 7 days of the 1st dose of study drug (Inhaled steroids for asthma, topical steroids, replacement/stress corticosteroids, or corticosteroids taken as premedication are allowed) Consumption of grapefruit or grapefruit products within 3 days prior to the first dose of study drug Patient receiving treatments strong CYP3A4 inhibitors or inducers (Appendix A) Positive for HIV and VHC Predisposing condition/currently exhibiting signs of bleeding Currently receiving anticoagulation therapy, exception of low-dose anticoagulation medications for prophylaxis Received aspirin within 7 days of start dose of study drug Active peptic ulcer disease / other potentially hemorrhagic esophagitis/gastritis Active immune thrombocytopenic purpura, autoimmune hemolytic anemia or history of being refractory to platelet transfusions (within 1 year of 1st dose of study drug) Uncontrolled cardiac, renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic disease, active systemic fungal infection; diagnosis of fever and neutropenia within 1 week of study drug administration A evidence of current/active malignancies other than ovarian cancer Pregnant or lactating women

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: ABT-263<br>oral Navitoclax (ABT-263) daily | Drug: ABT-263<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint is the progression-free survival (PFS) in the whole cohort of patients with a recurrent platinum-resistant ovarian cancer. |  | the time to progression (or death from any cause) from date of randomization until date of first documented progression or date of death from any cause,whichever came first, assessed up to 12 months. Evaluation at interim and final analyses. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bim expression level | Bim expression level expressed by immunohistochemistry on biopsy of relapsing tumor at inclusion | biopsy sample before initiation of treatment by ABT-263 and assessment within 6 months after end of inclusions | 
| Response rate | - Response rate defined by a complete response (CR), a partial response (PR) or a stable disease (SD) according to the RECIST v1.1 | evaluated every 6 weeks during treatment to progression or death for any cause.(during average 12 months)] | 
| Overall survival (OS) |  | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months. | 
| Incidence of Treatment-Emergent Adverse Events according to the NCI CTC AE version 4.0 | Toxicities | From date of treatment start until end of study participation (during average 12 months)] | 
| Peak Plasma Concentration of ABT-263 |  | 8-hour post-dose PK on D1 of C1 & 2. Dosage will be done within 12 months after end of inclusions | 
| Residual concentration of ABT-263 |  | Pre-dose 0 and cycles 3, 4, 6 . Dosage will be done within 12 months after end of inclusions |