Sorafenib in Treating Patients With Advanced or Recurrent Uterine Cancer

A Phase II Study of BAY 43-9006 in Advanced/Recurrent Uterine Carcinoma/Carcinosarcoma

Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. This phase II trial is studying how well sorafenib works 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