Temozolomide and Thalidomide in Treating Patients With Brain Metastases Secondary to Melanoma

Study Overview
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Brief Summary
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This phase II trial is studying how well giving temozolomide together with thalidomide works in treating patients with brain metastases secondary to melanoma. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. Combining temozolomide with thalidomide may kill more tumor cells

Detailed Description
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OBJECTIVES: Primary I. Determine the objective response rate in patients with brain metastases secondary to melanoma treated with temozolomide and thalidomide. Secondary I. Determine the toxic effects of and tolerance to this regimen in these patients. II. Determine the objective response rate in extracranial metastases of patients treated with this regimen. III. Determine the time to first disease progression (intra- or extracranial) in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive oral temozolomide once daily on days 1-42 and oral thalidomide once daily on days 1-56. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Patients achieving complete response (CR) receive 2 additional courses of therapy beyond CR. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually for up to 2 years. PROJECTED ACCRUAL: A total of 21-50 patients will be accrued for this study within 1.5 years.

Official Title
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A Phase II Study Of Temozolomide And Thalidomide In Patients With Metastatic Melanoma In The Brain

Conditions
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Recurrent Melanoma, Stage IV Melanoma, Tumors Metastatic to Brain

Intervention / Treatment
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* Drug: temozolomide
* Drug: thalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed metastatic melanoma Clinical evidence of brain metastases At least 1 unidimensionally measurable brain lesion at least 2.0 cm by conventional techniques OR at least 1.0 cm by spiral CT scan or MRI The following lesions are not considered measurable: Bone lesions Leptomeningeal disease Ascites Pleural/pericardial effusion Lymphangitis cutis/pulmonis Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions Lesions situated in a previously irradiated area, unless new growth is documented Performance status - CTC 0-1 Granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 AST and ALT no greater than 2.5 times upper limit of normal (ULN) Lactic dehydrogenase no greater than 2.5 times ULN Alkaline phosphatase no greater than 2.5 times ULN Creatinine no greater than 2 mg/dL No history of active angina No history of significant ventricular arrhythmia No history of deep vein thrombosis No myocardial infarction within the past 6 months No acute abnormality by EKG No uncontrolled arrhythmia No history of pulmonary embolism Not pregnant or nursing Negative pregnancy test Fertile patients must use 1 highly-effective and 1 additional method of contraception for 28 days before, during, and for 4 weeks after study participation No known HIV disease Thyroid-stimulating hormone normal Serum anticonvulsant levels normal (for patients on anticonvulsants) No frequent vomiting and/or any other medical condition (e.g., partial bowel obstruction) that would preclude oral medication intake No preexisting neuropathy greater than grade 1 No uncontrolled seizures No other concurrent medical condition that would preclude study participation At least 4 weeks since prior cytokines Biologic agents used as adjuvants, vaccines, and cellular therapies do not require a 4-week washout period No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF) No more than 1 prior chemotherapy regimen No prior chemotherapy for brain metastases No prior continuous daily temozolomide At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) No other concurrent chemotherapy No concurrent hormonal therapy except steroids and hormones administered for non-disease-related conditions (e.g., insulin for diabetes) or for control of intracranial edema from brain metastases See Disease Characteristics Prior whole brain radiotherapy (WBRT) allowed provided patient has progressive disease in a measurable CNS lesion Prior stereotactic radiotherapy allowed provided patient has progressive disease in a measurable CNS lesion At least 4 weeks since prior WBRT At least 3 weeks since prior stereotactic radiosurgery No concurrent radiotherapy At least 3 weeks since prior surgical resection No concurrent warfarin or heparin products or their derivatives No concurrent antiplatelet therapy (e.g., daily aspirin, ibuprofen, or clopidogrel bisulfate) No concurrent bisphosphonates (e.g., zoledronate)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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 (temozolomide, thalidomide)<br>Patients receive oral temozolomide once daily on days 1-42 and oral thalidomide once daily on days 1-56. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Patients achieving CR receive 2 additional courses of therapy beyond CR. | Drug: temozolomide<br>* Given orally<br>* Other names: TMZ;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 |
| --- | --- | --- |
| Response rate (defined as complete or partial) | 90% confidence intervals will be used. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first progression | Kaplan-Meier method will be used. | Up to 5 years | 
| Overall survival | Kaplan-Meier method will be used. | Up to 5 years |