Sorafenib in Treating Patients With Advanced or Recurrent Uterine Cancer

PRIMARY OBJECTIVES:

I. Determine the objective response rate in patients with advanced or recurrent uterine cancer treated with sorafenib.

II. Determine the toxic effects of this drug in these patients.

SECONDARY OBJECTIVES:

I. Determine progression-free survival of patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to histology (carcinoma vs carcinosarcoma).

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Inclusion criteria

• No prior sorafenib
• Histologically or cytologically confirmed uterine carcinoma or carcinosarcoma:

• Advanced or recurrent disease
• Not amenable to curative surgery or radiotherapy
• Measurable disease:

• At least 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan
• Tumor tissue block must be available
• No known brain metastases
• Performance status:

• ECOG 0-2 OR
• Karnofsky 60-100%
• Hematopoietic:

• Absolute neutrophil count >= 1,500/mm3
• Platelet count >= 100,000/mm3
• No bleeding diathesis
• Hepatic:

• Bilirubin normal
• AST and ALT =< 2.5 times upper limit of normal
• Renal:

• Creatinine =< 1.5 mg/dL OR
• Creatinine clearance >= 60 mL/min
• Cardiovascular:

• No uncontrolled hypertension, defined by 1 of the following:

• Blood pressure > 150/100 mm Hg
• Currently taking > 1 antihypertensive agent
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other active malignancy
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to sorafenib
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No swallowing dysfunction that would preclude study drug ingestion
• No other uncontrolled illness
• Prior biological response modifier therapy allowed
• No prior antiangiogenesis therapy
• No prior MAPK-signaling agents
• No prior vascular endothelial growth factor receptor (VEGFR) inhibitors
• No more than 1 prior chemotherapy regimen
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• Prior hormonal therapy allowed
• Prior radiotherapy allowed provided the only site of measurable disease was not located within the radiation port OR disease has progressed since completion of therapy
• Recovered from all prior therapy
• Concurrent warfarin allowed provided all of the following are true:

• Patient is therapeutic on a stable warfarin dose
• INR target range =< 3
• Patient is monitored with weekly INR testing
• No active bleeding or pathological condition that carries a high bleeding risk
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital)
• No concurrent rifampin
• No concurrent Hypericum perforatum (St. John's wort)
• No other concurrent investigational agents
• No other concurrent anticancer therapy
• More than 4 weeks since prior radiotherapy