Sorafenib in Treating Patients With Persistent or Recurrent Ovarian Epithelial or Peritoneal Cancer

Study Overview
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Brief Summary
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Sorafenib may stop the growth of tumor cells by stopping blood flow to the tumor and by blocking the enzymes necessary for their growth. This phase II trial is studying how well sorafenib works in treating patients with persistent or recurrent ovarian epithelial or peritoneal cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the efficacy of sorafenib in patients with persistent or recurrent ovarian epithelial or primary peritoneal carcinoma. II. Determine 6-month progression-free survival of patients treated with this drug. III. Determine the toxicity of this drug, in terms of frequency and severity of adverse events encountered, in these patients. SECONDARY OBJECTIVES: I. Determine the clinical response rate (partial and complete response) in patients treated with this drug. II. Determine the duration of progression-free and overall survival of patients treated with this drug. III. Correlate prognostic variables (platinum sensitivity, performance status, and histology [clear cell and mucinous type]) with response in patients treated with this drug. OUTLINE: This is a multicenter study. 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 are followed every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: Approximately 22-60 patients will be accrued for this study within 6-13 months.

Official Title
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A Phase II Evaluation of BAY 43-9006 (Sorafenib, Nexavar®, NCI-Supplied Agent, NSC #724772) in the Treatment of Persistent or Recurrent Epithelial Ovarian or Primary Peritoneal Carcinoma

Conditions
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Primary Peritoneal Carcinoma, Recurrent Ovarian Carcinoma

Intervention / Treatment
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* Other: Laboratory Biomarker Analysis
* Drug: Sorafenib Tosylate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed ovarian epithelial or primary peritoneal carcinoma Persistent or recurrent disease Measurable or evaluable disease Measurable disease is defined as at least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques (including palpation, plain x-ray, CT scan, or MRI) OR ≥ 10 mm by spiral CT scan Evaluable disease is defined as at least 1 of the following: CA 125 ≥ 2 times upper limit of normal (ULN) Ascites and/or pleural effusion attributed to tumor Solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST definition for target lesions Must have received 1 prior platinum-based chemotherapeutic regimen for primary disease, including carboplatin, cisplatin, or another organoplatinum compound Initial treatment may have included high-dose therapy, consolidation, or extended therapy administered after surgical or non-surgical assessment Platinum-resistant according to 1 of the following criteria: Treatment-free interval of < 12 months after platinum therapy Disease progression during platinum-based therapy Persistent disease after a platinum-based regimen Ineligible for higher priority GOG protocol (e.g., any active phase III GOG protocol for the same patient population) No brain metastases Performance status - GOG 0-2 (for patients who received 1 prior treatment regimen) Performance status - GOG 0-1 (for patients who received 2 prior treatment regimens) Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 No known bleeding diathesis Bilirubin ≤ 1.5 times ULN SGOT ≤ 2.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN Creatinine ≤ 1.5 times ULN No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No uncontrolled hypertension Able to take oral medication No bowel obstruction or persistent vomiting No requirement for parenteral feedings Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception during and for 3 months after study participation No sensory or motor neuropathy > grade 1 No active or ongoing infection requiring antibiotics No history of allergic reaction attributed to compounds of similar chemical or biological composition to sorafenib No serious chronic skin conditions (i.e., psoriasis or dermatitis) that would preclude study participation No psychiatric illness or social situation that would preclude study compliance No other uncontrolled illness No other invasive malignancy within the past 5 years except nonmelanoma skin cancer At least 3 weeks since prior immunologic agents for the malignancy More than 4 weeks since prior mouse antibodies (for patients with evaluable disease only) No concurrent prophylactic growth factors (e.g., filgrastim [G-CSF]) No concurrent prophylactic thrombopoietic agents except in the case of recurrent grade 4 thrombocytopenia No other concurrent biological agents for the primary tumor See Disease Characteristics More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered No prior non-cytotoxic chemotherapy for persistent or recurrent disease No concurrent chemotherapy for the primary tumor At least 1 week since prior hormonal therapy for the malignancy No concurrent hormonal therapy for the primary tumor Concurrent hormone replacement therapy allowed More than 4 weeks since prior radiotherapy and recovered No prior radiotherapy to > 25% of marrow-bearing areas No concurrent radiotherapy More than 4 weeks since prior surgery involving the peritoneum or pleura (for patients with evaluable disease only) Recovered from prior surgery At least 3 weeks since other prior therapy for the malignancy No more than 1 additional prior cytotoxic regimen for persistent or recurrent disease No prior sorafenib No prior anticancer treatment that would preclude study participation No concurrent therapeutic oral anticoagulation therapy (i.e., warfarin) Concurrent prophylactic anticoagulation (i.e., low-dose warfarin) for central venous access devices allowed provided INR is < 1.5 No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent investigational or commercial agents or therapies for the malignancy

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: Treatment (sorafenib tosylate)<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. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>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 |
| --- | --- | --- |
| Frequency and severity of adverse events as assessed by CTCAE v3.0 |  | Up to 5 years | 
| Progression-free survival | Will be evaluated using proportional hazards modeling and Fisher's exact test. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of overall survival | Will be evaluated using proportional hazards modeling and Fisher's exact test. | Up to 5 years | 
| Duration of progression-free survival | Will be evaluated using proportional hazards modeling and Fisher's exact test. | Up to 5 years | 
| Frequency of clinical response (complete and partial response) defined by RECIST criteria |  | Up to 5 years | 
| Prognostic variables (platinum sensitivity, performance status, and cellular histology [clear cell or mucinous type]) |  | Up to 5 years |