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
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
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.
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
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:
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:
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
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)
No concurrent combination antiretroviral therapy for HIV-positive patients
No other concurrent investigational or commercial agents or therapies for the malignancy