Sorafenib in Treating Patients With Advanced or Recurrent Uterine Cancer

Phase 2

Completed

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

Interventions: Drug: sorafenib tosylate

Registration Number: NCT00238121

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 56

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Objective Overall Response Rate	Up to 5 years	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Up to 5 years	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.
Duration of Response	Up to 5 years	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.
Progression Free Survival	Up to 5 years	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.

Trial Locations

Locations (7): City of Hope Medical Center
🇺🇸
Duarte, California, United States
Central Illinois Hematology Oncology Center
🇺🇸
Springfield, Illinois, United States
Juravinski Cancer Centre at Hamilton Health Sciences
🇨🇦
Hamilton, Ontario, Canada
University of Southern California
🇺🇸
Los Angeles, California, United States
Decatur Memorial Hospital
🇺🇸
Decatur, Illinois, United States
Cancer Centre of Southeastern Ontario at Kingston General Hospital
🇨🇦
Kingston, Ontario, Canada
University Health Network-Princess Margaret Hospital
🇨🇦
Toronto, Ontario, Canada