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.

Condition	Treatment or Intervention	Phase
Stage IV Melanoma Recurrent Melanoma	Drug: everolimus  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: growth factor antagonist therapy	Phase II

Further Study Details: 

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 weekly 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.

PROJECTED ACCRUAL: A total of 20-45 patients will be accrued for this study within 15.5 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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 12 hours before and 12 hours after study drug administration
• 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

Study chairs or principal investigators

Svetomir Markovic, MD, PhD,  Study Chair,  Mayo Clinic Cancer Center   
Ravi Rao, MD, MBBS,  Mayo Clinic Cancer Center   
Harold E. Windschitl, MD,  Coborn Cancer Center   
William J. Maples, MD,  Mayo Clinic - Jacksonville   
Michael K. Gornet, MD,  Mayo Clinic Scottsdale   
James N. Ingle, MD,  Mayo Clinic Cancer Center   
Edward T. Creagan, MD,  Mayo Clinic Cancer Center   
Judith S. Kaur, MD,  Mayo Clinic Cancer Center   
Barbara A. Pockaj, MD,  Mayo Clinic Scottsdale   
Evanthia Galanis, MD,  Mayo Clinic Cancer Center   
Charles L. Loprinzi, MD,  Mayo Clinic Cancer Center   
Henry Clement Pitot, MD,  Mayo Clinic Cancer Center   
Lori A. Erickson, MD,  Mayo Clinic Cancer Center   
Val J. Lowe, MD,  Mayo Clinic Cancer Center   
Jamie R. Merchan, MD,  Mayo Clinic Cancer Center   

Study ID Numbers:  CDR0000402871; NCCTG-N0377; NCT00098553
Record last reviewed:  November 2004
Last Updated:  February 4, 2005
Record first received:  December 7, 2004
ClinicalTrials.gov Identifier:  NCT00098553
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08