Sorafenib With or Without Paclitaxel and Carboplatin in Treating Patients With Recurrent Ovarian Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

Study Overview
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Brief Summary
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Sorafenib may stop the growth of tumor cells by blocking the enzymes necessary for their growth and by stopping blood flow to the tumor. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving sorafenib together with chemotherapy may kill more tumor cells. This randomized phase II trial is studying how well giving sorafenib together with paclitaxel and carboplatin works in treating patients with recurrent ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. (Sorafenib only group closed as of 10/10/2008).

Detailed Description
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PRIMARY OBJECTIVES : I. Compare the progression-free and overall survival rate of patients with recurrent platinum-sensitive ovarian epithelial, primary peritoneal, or fallopian tube cancer treated with sorafenib with or without carboplatin and paclitaxel. (Arm I [sorafenib only] closed to accrual 10/01/2008) II. Evaluate the response rate and time to disease progression in patients treated with these regimens. OUTLINE: This is a multicenter study. Patients are stratified according to performance status and participating center. ARM I (closed to accrual 10/01/2008): Patients receive oral sorafenib twice daily on days 1-28.Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression crossover to arm II. ARM II: Patients receive oral sorafenib twice daily on days 2-19. Patients also receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Official Title
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A Phase II Trial Of BAY 43-9006, A Novel Raf Kinase Inhibitor Plus Paclitaxel/Carboplatin In Women With Recurrent Platinum Sensitive Epithelial Ovarian, Peritoneal Or Fallopian Tube Cancer

Conditions
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Recurrent Fallopian Tube Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma

Intervention / Treatment
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* Drug: Carboplatin
* Drug: Paclitaxel
* Drug: Sorafenib Tosylate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of ovarian epithelial, primary peritoneal, or fallopian tube cancer Recurrent disease Must have received a prior platinum-based regimen Platinum-sensitive (treatment-free interval > 6 months) No more than 2 prior chemotherapy regimens Measurable disease At least 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan Not in a prior irradiation field No known brain metastases Performance status: ECOG 0-2 OR Karnofsky 80-100% Life expectancy: More than 12 weeks Hematopoietic: Absolute neutrophil count >= 1,500/mm3 Platelet count >= 100,000/mm3 Hemoglobin >= 9 g/dL No bleeding diathesis Hepatic: Bilirubin < 1.5 times upper limit of normal (ULN) AST or ALT =< 2 times ULN No history of allergic reaction attributed to compounds of similar chemical or biological composition to sorafenib or other agents used in the study Patients who have had a reaction to a taxane or a platinum and have not yet been rechallenged may undergo a desensitization regimen on study No hypersensitivity to paclitaxel or drugs using the vehicle Cremophor El: Prior hypersensitivity reaction to paclitaxel allowed provided rechallenged successfully Renal: Creatinine < 2 mg/dL Cardiovascular: Abnormal cardiac conduction (e.g., bundle branch block or heart block) allowed if stable for the past 6 months No symptomatic congestive heart failure No uncontrolled hypertension No cardiac arrhythmia No unstable angina pectoris; No myocardial infarction within the past 6 months Negative pregnancy test Fertile patients must use effective contraception Adequate intestinal function No concurrent requirements for IV hydration or nutritional support No active or ongoing infection No psychiatric illness or social situation that would preclude study compliance No other concurrent uncontrolled illness No other invasive malignancy with the past 5 years except nonmelanoma skin cancer More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered More than 3 weeks since prior hormonal therapy More than 4 weeks since prior radiotherapy and recovered No prior sorafenib No prior anticancer therapy that contraindicates study therapy No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine, or phenobarbital), rifampin, or Hypericum perforatum (St. John's wort) No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent therapeutic anticoagulation therapy Concurrent prophylactic low-dose warfarin allowed for maintenance of venous or arterial access devices No other concurrent anticancer therapies No other concurrent investigational agents Not pregnant or nursing

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (closed to accrual 10/10/2008)<br>Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression crossover to arm II | Drug: Sorafenib Tosylate<br>* Given orally<br>* Other names: sorafenib;|
| Experimental: Arm II<br>Patients receive oral sorafenib twice daily on days 2-19. Patients also receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. | Drug: Carboplatin<br>* Given IV<br>* Other names: Ribocarbo;Drug: Paclitaxel<br>* Given IV<br>* Other names: Taxol Konzentrat;Drug: Sorafenib Tosylate<br>* Given orally<br>* Other names: sorafenib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete and Partial Response Rate Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Patients should be reevaluated for response every 2 cycles (6 weeks). Patients who continue on Arm A of treatment for more than 12 months should be reevaluated for response every 3 cycles (9 weeks). In addition to a baseline scan, confirmatory scans should also be obtained 4 weeks following initial documentation of objective response. | after 6 weeks (2 cycles) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the Progression-free Survival Rate | Progression free survival (PFS) was measured by months from the date of treatment to the date of death or the date of progression, and censored at the date of last follow-up for those alive without progression. | up to 85 months of follow-up | 
| Overall Survival | Overall survival time, in months, is calculated from the date of treatment to date of death, and to date of last follow-up for those still alive. | up to 85 months of follow-up |