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

Study Overview
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Brief Summary
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This phase II trial is studying how well thalidomide works in treating patients with carcinosarcoma of the uterus that has come back or that does not go to remission (decrease or disappear but may still be in the body) despite treatment. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor.

Detailed Description
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OBJECTIVES: Primary 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 carcinosarcoma. II. Determine the nature and degree of toxicity of this drug in these patients. Secondary I. Determine the partial and complete response rates in patients treated with this drug. II. Determine the duration of PFS and overall survival of patients treated with this drug. III. Determine the effect of this drug on initial performance status and histological grade in these patients. IV. Correlate serum and plasma biomarkers, including vascular endothelial growth factor and basic fibroblast growth factor, with clinical outcome (i.e., 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 28 days 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. PROJECTED ACCRUAL: A total of 19-51 patients will be accrued for this study within 3 years.

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

Conditions
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Recurrent Uterine Corpus Sarcoma, Uterine Carcinosarcoma

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed uterine sarcoma Carcinosarcoma (malignant mixed müllerian tumor) Homologous or heterologous type Recurrent or persistent with documented disease progression after prior local therapy At least 1 unidimensionally measurable target lesion At least 20 mm by conventional techniques, including palpation, plain x-ray, CT scan, or MRI At least 10 mm by spiral CT scan Tumors within a previously irradiated field are considered non-target lesions Must have received 1 prior initial chemotherapy regimen (including high-dose ,consolidation, or extended therapy after surgical or nonsurgical assessment) for carcinosarcoma No documented brain metastases since diagnosis of cancer Patients with stable CNS deficits are allowed provided that there is no evidence of brain metastases on CT scan or MRI Ineligible for a higher priority Gynecologic Oncology Group (GOG) protocol (if one exists), including any active phase III GOG protocol for the same patient population 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 Not pregnant Negative pregnancy test Fertile patients must use at least 1 highly active method of contraception and 1 additional effective method of contraception for at least 4 weeks before, during, and for at least 4 weeks after study participation No 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 invasive malignancy within the past 5 years except nonmelanoma skin cancer At least 3 weeks since prior immunologic agents for uterine sarcoma No prior thalidomide See Disease Characteristics At least 3 weeks since prior chemotherapy for uterine sarcoma and recovered No more than 1 prior cytotoxic chemotherapy regimen for recurrent or persistent uterine sarcoma No prior non-cytotoxic chemotherapy for recurrent or persistent uterine sarcoma No concurrent bisphosphonates (e.g., zoledronate) At least 1 week since prior hormonal therapy for uterine sarcoma Concurrent hormone replacement therapy allowed See Disease Characteristics At least 3 weeks since prior radiotherapy for uterine sarcoma and recovered No prior radiotherapy to more than 25% of marrow-bearing areas See Disease Characteristics Recovered from prior surgery At least 3 weeks since any other prior therapy for uterine sarcoma No prior anticancer therapy that would preclude study
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 28 days in the absence of disease progression or unacceptable toxicity. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Thalidomide<br>* Given orally<br>* Other names: Thalomid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) > 6 Months | Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions. | Every other cycle for 6 months | 
| Frequency and Severity of Adverse Effects as Assessed by Common Toxicity Criteria (CTC) v2.0 |  | Each cycle during treatment and 30 days after the last treatment (average 4 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions. | Every other cycle until progression or death, up to 5 years. | 
| Tumor Response | RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate. | For those patients whose disease can be evaluated by physical examination, response was assessed prior to each 28-day cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle. (average = 4 months) | 
| Overall Survival | The observed length of life from entry into the study to death or the date of last contact. | From study entry to death or last contact, up to 5 years. | 
| Initial Performance Status | Performance status 0 = Fully active, able to carry on all pre-disease performance without restriction. Performance status 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of light or sedentary nature, e.g., light housework, office work. Performance status 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours. | baseline | 
| Initial Histologic Grade | G3 - Predominantly solid or entirely undifferentiated carcinoma. Not graded - tumor grade not reported. | Baseline |