Thalidomide in Treating Patients With Recurrent or Persistent Cancer of the Uterus

Study Overview
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Brief Summary
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Phase II trial to study the effectiveness of thalidomide in treating patients who have recurrent or persistent cancer of the uterus. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the antitumor cytostatic activity of thalidomide, as measured by the probability of progression-free survival (PFS) for at least 6 months, in patients with recurrent or persistent uterine leiomyosarcoma. II. Determine the nature and degree of the toxicity of this drug in these patients. III. Determine the partial and complete response rates in patients treated with this drug. IV. Determine the duration of PFS and overall survival of patients treated with this drug. V. Determine the effect of this drug on initial performance status in these patients. VI. Determine the effects of this drug at 4 weeks on endogenous angiogenesis factors (vascular endothelial growth factor and basic fibroblast growth factor) in plasma and urine of these patients. VII. Assess the association of endogenous angiogenesis factors with clinical outcome (PFS) in patients treated with this drug. OUTLINE: This is a multicenter study. Patients receive oral thalidomide once daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Official Title
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A Phase II Evaluation of Thalidomide (NSC #66847) in the Treatment of Recurrent or Persistent Leiomyosarcoma of the Uterus

Conditions
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Recurrent Uterine Corpus Sarcoma, Uterine Corpus Leiomyosarcoma

Intervention / Treatment
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* Drug: Thalidomide
* Other: Laboratory Biomarker Analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed primary uterine leiomyosarcoma (LMS) that is refractory to curative therapy or established treatments Recurrent or persistent disease At least 1 unidimensionally measurable target lesion At least 20 mm by conventional techniques, including palpation, plain x-ray, CT scan, or MRI OR at least 10 mm by spiral CT scan Tumors within a previously irradiated field are considered non-target lesions No smooth muscle tumor of uncertain malignant potential, including metastatic or recurrent disease from such a tumor Must have received 1 prior initial chemotherapy regimen (including high-dose, consolidation, or extended therapy after surgical or nonsurgical assessment) for uterine LMS Ineligible for a higher priority Gynecological Oncology Group (GOG) protocol (if one exists), including any active phase III protocol for the same patient population No documented brain metastases since diagnosis of cancer Patients with stable CNS deficits are allowed provided there are no brain metastases, as confirmed by CT scan or MRI Performance status - GOG 0-2 if received 1 prior therapy regimen Performance status - GOG 0-1 if received 2 prior therapy 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 Creatinine clearance greater than 60 mL/min No documented seizure disorders since diagnosis of cancer Patients with a history of seizure disorders are allowed provided that the seizures have been stable (i.e., no seizure within the past 12 months)while on an appropriately monitored treatment regimen No active infection requiring antibiotics No greater than grade 1 sensory or motor neuropathy No other prior invasive malignancy within the past 5 years except nonmelanoma skin cancer Not pregnant Negative pregnancy test Fertile patients must use at least 1 highly active method and 1 additional effective method of contraception for at least 4 weeks before, during, and for at least 4 weeks after study participation No prior thalidomide At least 3 weeks since prior immunologic agents for uterine LMS At least 3 weeks since other prior chemotherapy for uterine LMS and recovered No more than 1 prior cytotoxic chemotherapy regimen for recurrent or persistent uterine LMS No prior non-cytotoxic chemotherapy for recurrent or persistent uterine LMS At least 1 week since prior hormonal therapy for uterine LMS Concurrent hormone replacement therapy allowed At least 3 weeks since prior radiotherapy for uterine LMS and recovered No prior radiotherapy to more than 25% of bone marrow Recovered from recent prior surgery No prior anticancer therapy that would preclude study therapy At least 3 weeks since other prior therapy for uterine LMS No concurrent bisphosphonates (e.g., zoledronate)
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 (thalidomide)<br>Patients receive oral thalidomide once daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. | Drug: Thalidomide<br>* Given PO<br>* Other names: THAL;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | 6 months | 
| Frequency and severity of adverse effects as assessed by CTC |  | Up to 7 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of progression-free survival |  | Up to 7 years | 
| Duration of overall survival |  | Up to 7 years | 
| Frequency of clinical response (partial and complete response) |  | Up to 7 years |