RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have recurrent or persistent uterine carcinosarcoma.

Condition	Treatment or Intervention	Phase
uterine carcinosarcoma recurrent uterine sarcoma	Drug: imatinib mesylate  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the activity of imatinib mesylate, in terms of 6-month progression-free survival, in patients with recurrent or persistent uterine carcinosarcoma.
• Determine the frequency and severity of adverse effects of this drug in these patients.

Secondary

• Determine the distribution of overall and progression-free survival in patients treated with this drug.
• Determine the objective response rate (partial and complete response) in patients treated with this drug.
• Determine the effects of this drug on prognostic factors (initial performance status and histological grade) in these patients.

OUTLINE: This is an open-label, multicenter study.

Patients receive oral imatinib mesylate once or 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: A total of 19-51 patients will be accrued for this study within 15-30 months.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed uterine carcinosarcoma
• Malignant mixed Mullerian tumor, homologous or heterologous type
• Persistent or recurrent disease
• Progressive disease after prior local therapy
• At least 1 unidimensionally measurable lesion at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
• Presence of at least 1 target lesion (to be used to assess response)
• Tumors within a previously irradiated field are considered non-target lesions
• Received 1 prior chemotherapy regimen for carcinosarcoma
• Initial treatment may have included high-dose therapy, consolidation, or extended therapy administered after surgical or non-surgical assessment
• One additional prior cytotoxic regimen for recurrent or persistent disease allowed
• Ineligible for a higher priority GOG protocol
• No clinically apparent CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS: Age

• Not specified

Performance status

• GOG 0-2 (for patients who have received 1 prior regimen) OR
• GOG 0-1 (for patients who have received 2 prior regimens)

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT no greater than 2.5 times ULN
• Alkaline phosphatase no greater than 2.5 times ULN

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• No deep venous or arterial thrombosis within the past 6 weeks
• No myocardial infarction within the past 6 months
• No congestive heart failure requiring therapy

Pulmonary

• No pulmonary embolism within the past 6 weeks

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 3 months after study participation
• No history of seizures
• No sensory or motor neuropathy greater than grade 1
• No signs or symptoms of bowel dysfunction or obstruction
• No other invasive malignancy within the past 5 years except nonmelanoma skin cancer
• No active or uncontrolled infection requiring antibiotics
• No other concurrent severe disease that would preclude study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

• At least 3 weeks since prior immunologic agents directed at the malignant tumor
• No concurrent biologic agents directed at the malignant tumor
• No concurrent prophylactic growth factors
• No concurrent prophylactic thrombopoietic agents

Chemotherapy

• See Disease Characteristics
• Recovered from prior chemotherapy
• No prior non-cytotoxic chemotherapy for recurrent or persistent disease
• No concurrent chemotherapy directed at the malignant tumor

Endocrine therapy

• At least 1 week since prior hormonal therapy directed at the malignant tumor
• Concurrent hormone replacement therapy allowed
• No concurrent therapeutic corticosteroids

Radiotherapy

• See Disease Characteristics
• Recovered from prior radiotherapy

Surgery

• Recovered from prior surgery

Other

• At least 3 weeks since other prior therapy directed at the malignant tumor
• No prior imatinib mesylate
• No prior cancer treatment that would contraindicate study therapy
• No concurrent therapeutic anticoagulation with warfarin
• No concurrent amifostine or other protective agents
• No concurrent phenytoin, phenobarbital, or carbamazepine
• No other concurrent therapy directed at the malignant tumor
• No other concurrent investigational drugs

Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States; Recruiting
New York
      SUNY Downstate Medical Center, Brooklyn,  New York,  11203,  United States; Recruiting
North Carolina
      Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill,  North Carolina,  27599-7570,  United States; Recruiting
Ohio
      Charles M. Barrett Cancer Center at University Hospital, Cincinnati,  Ohio,  45267-0520,  United States; Recruiting
Pennsylvania
      Abington Memorial Hospital, Abington,  Pennsylvania,  19001-3788,  United States; Recruiting

Study chairs or principal investigators

Warner Huh, MD,  Study Chair,  UAB Comprehensive Cancer Center   
William E. Winter, MD,  Brooke Army Medical Center   

Study ID Numbers:  CDR0000346361; GOG-0230C; NCT00075400
Record last reviewed:  December 2004
Last Updated:  April 4, 2005
Record first received:  January 9, 2004
ClinicalTrials.gov Identifier:  NCT00075400
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08