Sorafenib in Treating Patients With Advanced or Recurrent Uterine Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Recurrent Uterine Sarcoma, Stage III Uterine Sarcoma, Stage IV Uterine Sarcoma, Uterine Carcinosarcoma

Intervention / Treatment
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* Drug: sorafenib tosylate


Participation Criteria
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Eligibility Criteria
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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

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<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. | Drug: sorafenib tosylate<br>* Given orally<br>* Other names: SFN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Overall Response Rate | Response was defined using the Response Evaluation Criteria in Solid Tumors (RECIST, http://www.ncbi.nlm.nih.gov/pubmed/10655437#): Complete Response(CR), disappearance of all target lesions; Partial Response(PR), at least a 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)=CR+PR. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Defined as the time from the first day of therapy to the date of death. If the patient was lost to follow-up, survival was censored on the last date the patient was known to be alive. | Up to 5 years | 
| Progression Free Survival | Defined as the time from the first day of treatment until the date PD(progressive disease) or death is first reported. Patients who died without a reported prior progression was considered to have progressed on the day of their death. Patients who did not progress was censored at the day of their last tumor assessment. According to RECIST, progressive disease(PD) is defined as at least a 20% increase in the sum of the longest diameter of target lesions. | Up to 5 years | 
| Duration of Response | Duration of response was measured from the time measurement criteria are met for CR(complete response)/PR(partial response), whichever was first recorded, until the first date that PD(progressive disease) was objectively documented. According to the RECIST: Complete Response(CR), disappearance of all target lesions; Partial Response(PR), at least a 30% decrease in the sum of the longest diameter of target lesions; progressive disease(PD), at least a 20% increase in the sum of the longest diameter of target lesions. | Up to 5 years |