Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Lovastatin in Treating Patients at High Risk of Recurrent Melanoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Biomarker/Laboratory analysis, Treatment Active 18 and over NCI UCIRVINE-UCI03-1-01 UCI03-1-01, UCIRVINE-2006-4937, NCT00462280

Objectives

Primary

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

Secondary

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

Entry Criteria

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

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)

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

Expected Enrollment

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

Outcomes

Histopathologic regression of atypical nevi

Overall nevus number as assessed by photos of patients’ backs pre and post treatment
SIAscopic parameters
Molecular biomarkers

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.

Trial Contact Information

Trial Lead Organizations

Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center

Frank Meyskens, MD, FACP, Protocol chair		Ph: 714-456-6310 Email: flmeyske@uci.edu

U.S.A.
California
	Orange
	Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
		Clinical Trials Office - Chao Family Comprehensive Cancer Center	Ph:  877-UC-STUDY
			Email: ucstudy@uci.edu
Florida
	Tampa
	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
		Clinical Trials Office - H. Lee Moffitt Cancer Center and Reseach Institute	Ph:  800-456-7121
			Email: canceranswers@moffitt.org
Utah
	Salt Lake City
	Huntsman Cancer Institute at University of Utah
		Clinical Trials Office - Huntsman Cancer Institute at University of Utah	Ph:  801-581-4477
			Email: clinical.trials@hci.utah.edu

Registry Information
Official Title		A Randomized Double-Blind, Placebo-Controlled Phase II Clinical Trial of Lovastatin for Various Endpoints of Melanoma Pathobiology
Trial Start Date		2007-05-16
Registered in ClinicalTrials.gov		NCT00462280
Date Submitted to PDQ		2007-03-16
Information Last Verified		2008-08-08
NCI Grant/Contract Number		CA62203, CN35160