Imatinib Mesylate in Treating Patients With Recurrent or Persistent Uterine Carcinosarcoma

• Progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
• Severity of adverse effects as assessed by NCI CTCAE version 3.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

• Frequency of adverse events [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
• Progression free survival [ Time Frame: From study entry until disease progression, death or date of last contact, assessed up to 5 years ] [ Designated as safety issue: No ]
  Compared using a logrank test and a Cox proportional hazards model while adjusting for initial performance status and histological grade.
• Overall survival [ Time Frame: The observed length of life from entry into the study to death or the date of last contact, assessed up to 5 years ] [ Designated as safety issue: No ]
  Compared using a logrank test and a Cox proportional hazards model while adjusting for initial performance status and histological grade.
• Clinical response (partial and complete) as assessed by RECIST [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have recurrent or persistent uterine carcinosarcoma. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth

PRIMARY OBJECTIVES:

I. Determine the activity of imatinib mesylate, in terms of 6-month progression-free survival, in patients with recurrent or persistent uterine carcinosarcoma.

II. Determine the frequency and severity of adverse effects of this drug in these patients.

SECONDARY OBJECTIVES:

I. Determine the distribution of overall and progression-free survival in patients treated with this drug.

II. Determine the objective response rate (partial and complete response) in patients treated with this drug.

III. 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.

• Recurrent Uterine Sarcoma
• Uterine Carcinosarcoma

• Drug: imatinib mesylate
  Given orally
  Other Names:

  • CGP 57148
  • Gleevec
  • Glivec
• Other: laboratory biomarker analysis
  Correlative studies

Inclusion Criteria:

• 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
• Performance status - GOG 0-2 (for patients who have received 1 prior regimen)
• Performance status - GOG 0-1 (for patients who have received 2 prior regimens)
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• 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
• Creatinine no greater than 1.5 times ULN
• 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
• No pulmonary embolism within the past 6 weeks
• 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
• 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
• 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
• At least 1 week since prior hormonal therapy directed at the malignant tumor
• Concurrent hormone replacement therapy allowed
• No concurrent therapeutic corticosteroids
• See Disease Characteristics
• Recovered from prior radiotherapy
• Recovered from prior surgery
• 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