S0508: Thalidomide and Temozolomide in Treating Patients With Stage IV Melanoma That Cannot Be Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Thalidomide may stop the growth of melanoma by blocking blood flow to the tumor. It may also stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving thalidomide together with temozolomide may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving thalidomide together with temozolomide works in treating patients with stage IV melanoma that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Determine the 6-month progression-free survival of patients with unresectable stage IV malignant cutaneous melanoma treated with thalidomide and temozolomide. Determine the objective response (confirmed and unconfirmed complete response and partial response) in patients with measurable disease treated with this regimen. Determine the overall survival of patients treated with this regimen. Determine the qualitative and quantitative toxic effects of this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive oral thalidomide once daily on days 1-56 and temozolomide once daily on days 1-42. Courses repeat every 56 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at week 9, every 2 months until disease progression, and then every 6 months until 3 years from study entry. PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study within 14 months.

Official Title
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A Phase II Trial of Combination Thalidomide Plus Temozolomide in Patients With Metastatic Malignant Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Drug: temozolomide
* Drug: thalidomide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed malignant cutaneous melanoma Unresectable, stage IV disease Unknown primary allowed Measurable or non-measurable disease If all known sites of disease are within a previously irradiated port, disease progression must be clearly demonstrated No brain metastases by CT scan or MRI within the past 42 days Prior brain metastasis allowed provided both of the following criteria are met: Completely resected and free of disease Treated with whole brain radiotherapy and completed treatment at least 28 days ago PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-1 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,000/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9 g/dL (transfusions allowed) Hepatic Bilirubin ≤ 3 times upper limit of normal (ULN) SGOT or SGPT ≤ 2.5 times ULN (5 times ULN if liver metastases are present) Renal Creatinine ≤ 1.5 times ULN Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective double-method contraception for 4 weeks before, during, and for 4 weeks after study participation No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission No history of allergic reaction to dacarbazine PRIOR CONCURRENT THERAPY: Biologic therapy No prior thalidomide for stage IV disease At least 28 days since prior biological therapy At least 28 days since prior immunotherapy At least 28 days since prior adjuvant interferon alfa Chemotherapy No prior temozolomide or dacarbazine for stage IV disease At least 28 days since prior chemotherapy Endocrine therapy At least 28 days since prior hormonal therapy Radiotherapy See Disease Characteristics At least 28 days since prior radiotherapy Surgery See Disease Characteristics At least 28 days since prior surgery for primary and stage IV disease Other No more than 1 prior systemic therapy regimen for stage IV disease At least 28 days since other prior systemic therapy

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: Thalidomide and Temozolomide<br>Patients receive oral thalidomide once daily on days 1-56 and temozolomide once daily on days 1-42. Courses repeat every 56 days in the absence of disease progression or unacceptable toxicity. | Drug: temozolomide<br>* 75 mg/m^2/day PO daily for 6 weeks followed by a 2-week break<br>Drug: thalidomide<br>* 200 mg/day PO daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival at 6 months |  | 6 months after registration | 
| Objective response (confirmed and unconfirmed complete and partial responses) |  | Week 9, every 8 weeks thereafter until progression | 
| 6-month overall survival |  | six months after registration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV melanoma