Everolimus in Treating Patients With Stage IV Melanoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as everolimus, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may also stop the growth of melanoma by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well everolimus works in treating patients with stage IV melanoma.

Detailed Description
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OBJECTIVES: Primary Determine the median time to disease progression in patients with stage IV malignant melanoma treated with everolimus. Secondary Determine the median overall survival of patients treated with this drug. Determine the clinical benefit rates (i.e., stable disease, partial remission, and complete response rates) in patients treated with this drug. Determine the toxicity profile of this drug in these patients. Determine changes in serum vascular endothelial growth factor levels in patients treated with this drug. OUTLINE: This is a multicenter study. Patients receive oral everolimus once daily for 8 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months until disease progression and then every 4 months for up to 5 years after registration.

Official Title
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Phase II Trial Of RAD-001 In Metastatic Malignant Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Drug: everolimus


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed malignant melanoma for which no known standard or potentially curative therapy exists or has been proven to extend life expectancy Stage IV disease Measurable disease At least 1 lesion ≥ 20 mm by CT scan or MRI OR ≥ 10 mm by spiral CT scan No intracranial disease PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy At least 12 weeks Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9.0 g/dL No bleeding diathesis Hepatic AST ≤ 3 times upper limit of normal (ULN) Alkaline phosphatase ≤ 3 ULN INR ≤ 1.5 Renal Creatinine ≤ 1.5 times ULN Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Willing to refrain from foods high in fat content No uncontrolled infection No immunosuppression from any cause (e.g., known HIV infection) No other malignancy within the past 5 years except basal cell or squamous cell skin cancer treated with local resection only No other severe condition that would preclude study participation or compliance PRIOR CONCURRENT THERAPY: Biologic therapy More than 4 weeks since prior immunotherapy or biologic therapy Chemotherapy More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered No prior sirolimus or its analogues for any indication No other concurrent chemotherapy Endocrine therapy No concurrent steroids Radiotherapy More than 4 weeks since prior radiotherapy to head and neck area More than 4 weeks since prior radiosurgery No prior radiotherapy to > 30% of bone marrow No concurrent radiotherapy Surgery Not specified Other At least 1 week since prior and no concurrent CYP3A4 inducers No concurrent warfarin No concurrent cytotoxic agents No other concurrent experimental drugs No other concurrent immunosuppressive 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: everolimus<br>Patients receive oral everolimus once daily for 8 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months until disease progression and then every 4 months for up to 5 years after registration. | Drug: everolimus<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with progression-free disease at 16 weeks |  | at 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median overall survival |  | Up to 5 years | 
| Tumor response rate for 2 consecutive evaluations at least 8 weeks apart |  | Up to 5 years | 
| Toxicity as measured by CTCAE v. 3.0 |  | Up to 5 years | 
| disease progression |  | at 16 weeks | 

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