Temozolomide, Thalidomide, and Lomustine in Treating Patients With Unresectable Stage III or Stage IV Melanoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as temozolomide and lomustine, use 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 and thalidomide with lomustine may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining temozolomide and thalidomide with lomustine in treating patients who have unresectable stage III or stage IV melanoma.

Detailed Description
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OBJECTIVES: Primary Determine the antitumor activity of temozolomide, thalidomide, and lomustine, in terms of objective response rate, in patients with unresectable stage III or stage IV melanoma. Secondary Determine the toxicity profile of this regimen in these patients. Determine the duration of response and overall survival of patients treated with this regimen. OUTLINE: Patients receive oral temozolomide on days 1-42, oral thalidomide on days 1-56, and oral lomustine on days 1 and 29. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 12-35 patients will be accrued for this study within 2 years.

Official Title
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A Phase II Study of Temozolomide, Thalidomide, and Lomustine in the Treatment of Advanced Melanoma

Conditions
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Intraocular Melanoma, Melanoma (Skin)

Intervention / Treatment
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* Drug: lomustine
* Drug: temozolomide
* Drug: thalidomide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed metastatic malignant melanoma Unresectable stage III OR stage IV disease Ocular, mucosal, and cutaneous melanoma allowed Measurable disease Indicator lesions within a prior radiotherapy field must have recent evidence of disease progression Indicator lesions must be distinct from the surgical and/or radiation changes induced by prior local therapies No more than 2 symptomatic hemorrhagic lesions in the brain No hemorrhagic lesion(s) greater than 1 cm in diameter PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 80-100% Life expectancy Not specified Hematopoietic Absolute granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic Bilirubin no greater than 2 times upper limit of normal (ULN) SGOT and SGPT no greater than 2 times ULN Alkaline phosphatase no greater than 2 times ULN Lactic dehydrogenase no greater than 2 times ULN Renal Creatinine no greater than 2 mg/dL Cardiovascular No history of severe cardiovascular disease No myocardial infarction within the past 6 months No unstable angina No New York Heart Association class III or IV congestive heart failure No ventricular arrhythmia No uncontrolled arrhythmia Gastrointestinal No frequent vomiting No other medical condition that would preclude oral medication intake (e.g., partial bowel obstruction) Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception during and for 4 weeks after study participation HIV negative No AIDS-related illness No serious infection requiring IV antibiotics No other uncontrolled medical illness that would preclude study participation No other malignancy within the past 2 years except nonmelanoma skin cancer, carcinoma in situ of the cervix, or T1a or b prostate cancer meeting all of the following criteria: Detected incidentally at transurethral resection of the prostate (TURP) Comprises less than 5% of resected tissue Prostate-specific antigen normal since TURP PRIOR CONCURRENT THERAPY: Biologic therapy At least 3 weeks since prior immunotherapy or biologic therapy No concurrent immunotherapy Chemotherapy No prior systemic chemotherapy for melanoma No other concurrent chemotherapy Endocrine therapy Not specified Radiotherapy See Disease Characteristics At least 3 weeks since prior focused radiotherapy for brain metastases At least 3 weeks since prior radiosurgery At least 4 weeks since prior whole brain radiotherapy At least 3 weeks since prior interstitial brachytherapy No concurrent radiotherapy Surgery See Disease Characteristics At least 3 weeks since prior surgery for brain metastases At least 3 weeks since prior surgery requiring general anesthesia Other Recovered from all prior therapies

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: lomustine|nan|
|Drug: temozolomide|nan|
|Drug: thalidomide|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 III melanoma, stage IV melanoma, recurrent melanoma, iris melanoma, ciliary body and choroid melanoma, medium/large size, ciliary body and choroid melanoma, small size, extraocular extension melanoma, recurrent intraocular melanoma