Official Title: “A Randomized Double-Blind, Placebo-Controlled Phase II Clinical Trial of Lovastatin for Various Endpoints of Melanoma Pathobiology”

RATIONALE: The use of lovastatin may slow disease progression in patients at high risk of recurrent melanoma. It is not yet known whether lovastatin is more effective than a placebo in treating patients at high risk of recurrent melanoma.

PURPOSE: This randomized phase II trial is studying lovastatin to see how well it works compared to a placebo in treating patients at high risk of recurrent melanoma.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control

OBJECTIVES:

Primary - Compare histopathologic regression of atypical nevi in patients with atypical nevi and a history of primary melanoma receiving lovastatin vs placebo.

Secondary - Compare clinical regression of atypical nevi in patients treated with these regimens. - Compare changes in nevi numbers on the backs of patients treated with these regimens. - Compare reduction of total melanin, dermal melanin, and vascularization in patients treated with these regimens. - Compare number of molecular biomarkers in patients treated with these regimens. - Correlate serum markers known to be affected by lovastatin with the endpoints chosen above. - Determine the safety and tolerability of these regimens in these patients.

OUTLINE: This is a randomized, placebo-controlled, double blind, multicenter study. Patients are stratified according to nevi status (two atypical nevi matched for atypia vs one large [> 8 mm diameter] nevus with one other atypical nevus). Patients are randomized to 1 of 2 treatment arms. - Arm I: Patients receive oral lovastatin once daily for up to 6 months in the absence of disease progression or unacceptable toxicity. - Arm II: Patients receive oral placebo once daily for up to 6 months in the absence of disease progression or unacceptable toxicity.

Biopsies and blood samples are collected periodically throughout study and are examined by histopathologic evaluation for molecular biomarker analysis, including VEGF, Ki-67, p21, and RelA.

After completion of study therapy, patients are followed at 2 weeks.

PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: lovastatin
  • Given orally
• Drug: placebo
  • Given orally

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Arm I
  • Patients receive oral lovastatin once daily for up to 6 months in the absence of disease progression or unacceptable toxicity.
• Placebo Comparator: Arm II
  • Patients receive oral placebo once daily for up to 6 months in the absence of disease progression or unacceptable toxicity.

Primary Measures

• Histopathologic regression of atypical nevi
  • Safety Issue?: No

Secondary Measures

• Overall nevus number as assessed by photos of patients' backs pre and post treatment
  • Safety Issue?: No
• SIAscopic parameters
  • Safety Issue?: No
• Molecular biomarkers
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• History of melanoma meeting the following criteria:
• Breslow's thickness < 4.00 mm with no evidence of regional nodal involvement
• Sentinel node biopsy strongly encouraged if the lesion is > 1.00 mm or ulcerated
• No untreated melanoma of any stage or locally advanced (> 4 mm) or metastatic (stage III or IV) melanoma
• Patients with melanoma may be considered for this clinical trial after complete resection of stage I or II melanoma if they have declined or are ineligible to go on any available adjuvant clinical trials
• Presence of ≥ 2 clinically atypical nevi in locations that can be easily biopsied

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-1 or Karnofsky PS 70-100%
• WBC ≥ 3,000/mm³
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal
• Creatinine normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of allergic reactions to compounds of similar chemical or biological composition to lovastatin
• No clinically significant unrelated systemic illness
• No medical or psychosocial condition that, in the opinion of the investigator, would limit study compliance
• No other malignancies within the past 5 years except for those meeting all of the following criteria:
• Currently without evidence of disease
• No treatment for invasive malignancy within the past 6 months
• No current or planned therapy
• Expected disease-free survival of ≥ 5 years

PRIOR CONCURRENT THERAPY:

• More than 3 months since prior and no concurrent adjuvant therapy or experimental therapy for melanoma
• More than 3 months since prior and no other concurrent lipid lowering agents of any type
• No chronic use of any of the following:
• Itraconazole
• Ketoconazole
• Erythromycin
• Clarithromycin
• Telithromycin
• HIV protease inhibitors
• Nefazodone
• Cyclosporine
• Gemfibrozil and other fibrates
• Danazol
• Amiodarone
• Verapamil
• Coumarin anticoagulants
• Niacin (nicotinic acid) > 1 g/day
• Large quantities of grapefruit juice (> 1 quart daily)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Chao Family Comprehensive Cancer Center

Overall Clinical Trial Officials and Contacts

Frank L. Meyskens, MD, FACP Study Chair Chao Family Comprehensive Cancer Center  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00462280

Study ID Number: CDR0000540141

ClinicalTrials.gov Identifier: NCT00462280

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database