Temozolomide and Radiation Therapy in Treating Patients With Stage IV Malignant Melanoma With Measurable and Unresectable Cancer of the Central Nervous System

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as temozolomide, use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining temozolomide with radiation therapy may make the tumor cells more sensitive to radiation therapy and kill more tumor cells. PURPOSE: This phase II trial is studying how well giving temozolomide together with radiation therapy works in treating patients with stage IV malignant melanoma with measurable and unresectable cancer limited to the central nervous system.

Detailed Description
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OBJECTIVES: Primary Determine the response rate in patients with stage IV malignant melanoma with measurable and unresectable disease of the central nervous system treated with temozolomide and radiotherapy. Secondary Determine the safety of this regimen in these patients. Determine the survival of patients treated with this regimen. Determine the effect of this regimen on performance status and mental status of these patients. Determine the response of extra-cranial disease in patients treated with this regimen. OUTLINE: Patients receive concurrent chemoradiotherapy comprising whole brain radiotherapy daily on days 1-5, 8-13, and 16-21 and oral temozolomide daily on days 1-5. Subsequent treatment with temozolomide repeats every 4 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months. PROJECTED ACCRUAL: A total of 18-41 patients will be accrued for this study within 13-30 months.

Official Title
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A Systemic Temozolomide Treatment Of Melanoma Present In The Central Nervous System

Conditions
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Melanoma (Skin), Metastatic Cancer

Intervention / Treatment
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* Drug: temozolomide
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed stage IV malignant melanoma with measurable and unresectable disease limited to the central nervous system (CNS) Study entry within 14 days of diagnosis of brain metastases Recursive partitioning analysis class I or II Disease for which no known standard therapy exists that is potentially curative or proven capable of extending life expectancy No meningeal carcinomatosis based on imaging studies or on positive results from CSF analysis No evidence of metastatic disease outside of the CNS PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 70-100% Hematopoietic Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 9.0 g/dL Hepatic AST no greater than 3 times upper limit of normal (ULN) Alkaline phosphatase no greater than 3 times ULN Renal Creatinine no greater than 1.5 times ULN Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No concurrent uncontrolled infection No other malignancy within the past 5 years except basal cell or squamous cell skin cancer treated with local resection only No prior allergy or intolerance to dacarbazine No hypersensitivity to temozolomide or any of its components PRIOR CONCURRENT THERAPY: Biologic therapy More than 4 weeks since prior biologic therapy More than 4 weeks since prior immunotherapy Chemotherapy No prior temozolomide More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered Endocrine therapy Concurrent steroids allowed if dose stable for at least 7 days prior to CNS imaging Radiotherapy More than 4 weeks since prior radiotherapy No prior radiotherapy to more than 15% of the bone marrow No prior radiotherapy to the head and neck area No prior radiosurgery

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: radiation + temozolomide<br>Patients receive concurrent chemoradiotherapy comprising whole brain radiotherapy daily on days 1-5, 8-13, and 16-21 and oral temozolomide daily on days 1-5. Subsequent treatment with temozolomide repeats every 4 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months. | Drug: temozolomide<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed response rate |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | Up to 5 years | 
| Overall survival |  | Up to 5 years | 
| Change in performance status |  | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV melanoma, recurrent melanoma, tumors metastatic to brain