Temozolomide With or Without Radiation Therapy to the Brain in Treating Patients With Stage IV Melanoma That Is Metastatic to the Brain

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy 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. It is not yet known if chemotherapy is more effective with or without radiation therapy in treating brain metastases. PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy with or without radiation therapy to the brain in treating patients who have stage IV melanoma with asymptomatic brain metastases.

Detailed Description
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OBJECTIVES: Compare the efficacy of temozolomide with or without radiotherapy in terms of overall survival in patients with stage IV melanoma with asymptomatic brain metastases. Compare the time to appearance of neurological symptoms in patients treated with these regimens. Compare the progression-free survival of patients treated with these regimens. Compare the quality of life and quality-adjusted survival of patients treated with these regimens. Compare the toxicity of these regimens in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to LDH levels (less than 225 U/L vs 225 U/L or more), concurrent metastases (visceral vs soft tissue), and participating center. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral temozolomide once daily on days 1-5. Treatment continues every 4 weeks for a maximum of 1 year in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive temozolomide as in arm I and whole brain radiotherapy on days 8-12 and 15-19 during the first course of chemotherapy. Quality of life is assessed before beginning each course and then every 4 weeks after completion of study drug. Patients are followed every 4 weeks. PROJECTED ACCRUAL: A total of 250 patients will be accrued for this study within 2 years.

Official Title
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Temozolomide Versus Temozolomide + Whole Brain Radiation In Stage IV Melanoma Patients With Asymptomatic Brain Metastases

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 unresectable metastatic melanoma Must have asymptomatic brain metastasis that is not amenable to surgery or stereotactic radiosurgery (gamma knife, Linac) Must have concurrent visceral/soft tissue metastases At least 1 site of measurable disease (not necessarily the brain metastasis) Documented evidence of disease progression defined by 1 of the following conditions: More than 25% increase in the size of at least 1 measurable lesion Appearance of a new lesion A significant increase in the size of nonmeasurable disease No neurological symptoms, including signs of elevated intracranial pressure PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 10 g/dL Hepatic: Bilirubin less than 1.5 times upper limit of normal (ULN) SGOT or SGPT less than 3 times ULN Alkaline phosphatase less than 3 times ULN Renal: Urea less than 1.5 times ULN Creatinine less than 1.5 times ULN Other: No frequent vomiting or medical condition (e.g., partial bowel obstruction) that would interfere with oral medication intake No other prior or concurrent malignancy except surgically cured carcinoma in situ of the cervix or basal cell or squamous cell skin cancer No uncontrolled infection HIV negative No AIDS-related illness Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No psychological, familial, sociological, or geographical condition that would preclude study PRIOR CONCURRENT THERAPY: Biologic therapy: Prior cytokine via isolated limb perfusion for local-regional melanoma allowed No other prior cytokine for metastatic melanoma No concurrent colony-stimulating factors, including epoetin alfa or filgrastim (G-CSF) No other concurrent immunologic or biologic therapy Chemotherapy: Prior chemotherapy via isolated limb perfusion for local-regional melanoma allowed No other prior chemotherapy for metastatic melanoma No other concurrent chemotherapy Endocrine therapy: Concurrent corticosteroids allowed during radiotherapy (arm II only) No concurrent hormonal therapy Radiotherapy: See Disease Characteristics No other concurrent radiotherapy Surgery: See Disease Characteristics Recovered from the effects of any prior major surgery Other: No other concurrent investigational drugs

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
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: temozolomide|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 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