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

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.

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