Know Cancer

forgot password

A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial of Lovastatin for Various Endpoints of Melanoma Pathobiology

Phase 2
18 Years
Open (Enrolling)
Precancerous Condition, Stage 0 Melanoma, Stage I Melanoma, Stage II Melanoma

Thank you

Trial Information

A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial of Lovastatin for Various Endpoints of Melanoma Pathobiology


I. To evaluate the primary endpoint of the trial, by analysis of histopathologic regression
of atypical nevi in response to a 6-month trial of oral (PO) lovastatin vs. placebo in
subjects with atypical nevi.


I. To evaluate clinical regression of atypical nevi in the lovastatin vs. placebo group.

II. To evaluate the secondary endpoint of changes in nevi numbers on subjects' backs in the
lovastatin vs. placebo groups.

III. To evaluate a number of molecular biomarkers as secondary endpoints in the lovastatin
vs. placebo groups.

IV. To evaluate the correlation of serum markers known to be affected by lovastatin with the
endpoints chosen above.

V. To evaluate the safety and tolerability of the dosing regimen, and the dose escalation.

OUTLINE: Patients are randomized into 1 of 2 treatment arms.

ARM I: Patients receive lovastatin PO once daily (QD) for up to 6 months in the absence of
disease progression or unacceptable toxicity.

ARM II: Patients receive placebo PO QD for up to 6 months in the absence of disease
progression or unacceptable toxicity.

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

Inclusion Criteria:

- Presence of at least 2 clinically atypical nevi on the body that are reasonably
matched in regards to level of clinical atypia, or one atypical mole and another
atypical mole >= 8 mm in diameter (for this pair the two moles do not have to be
closely matched and only one of them must be >= 8 mm in diameter)

- A history of melanoma is not required for study entry

- Patients with completely resected stage I or II who have not received adjuvant
therapy in the past 3 months

- Eastern Cooperative Oncology Group (ECOG) performance status of 1 or better
(Karnofsky > 70%)

- Leukocytes >= 3,000/uL

- Absolute neutrophil count >= 1,500/uL

- Platelets >= 100,000/uL

- Total bilirubin within normal institutional limits

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
=< 2.5 X within normal limits

- Creatinine within normal institutional limits

- Ability to understand and the willingness to sign the written informed consent

- Subjects willing and able to participate for the full duration of the study

- For women of child-bearing potential (women are considered not of childbearing
potential if they are at least 2 years post-menopausal and/or surgically sterile),

- has been using adequate contraception (abstinence, intrauterine device [IUD],
birth control pills, or spermicidal gel with diaphragm or condom) since her last
menses and will use adequate contraception during the study

- is not lactating, and

- has had a documented negative serum pregnancy test within 30 days prior to the
first dose of study medication Should a woman become pregnant or suspect she is
pregnant while participating in this study, she will be taken off study and be
advised to inform her treating physician immediately; a telephone follow-up with
the subject post-delivery will be completed to obtain outcome of pregnancy

- Men partnered with a female of child-bearing age must agree to use adequate
contraception while on the study (i.e. abstinence, IUD, birth control pills, or
spermicidal gel with diaphragm or condom)

Exclusion Criteria:

- Subjects with untreated melanoma of any stage or locally advanced (>= 4 mm in
Breslow's thickness) or metastatic (stage III or IV) melanoma; subjects with melanoma
may be considered for trial after complete resection of Stage I or II melanoma and
those who have declined or are ineligible to go on any available adjuvant clinical
trials known to the investigators or the subjects are eligible

- Subjects who are on adjuvant therapy or experimental therapy for melanoma currently
or within the last 3 months prior to enrollment into this study

- Subjects currently or within the last three months before enrollment on lipid
lowering agents of any type

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to lovastatin

- Clinically significant unrelated systemic illness

- Subjects with any medical or psychosocial condition that, in the opinion of the
investigator, could jeopardize his/her participation in and compliance with the study

- Subjects may not be receiving any other investigational agents

- Pregnant or breast feeding females, or females of child bearing age not using a
reliable method of contraception (use of lovastatin is contraindicated in pregnancy)

- Subjects who have been diagnosed with malignancies other than cutaneous melanoma,
cutaneous basal cell carcinoma, or cutaneous squamous cell carcinoma within 5 years
of study entry, unless they:

- are currently without evidence of disease

- have not received treatment for invasive malignancy in the last 6 months

- have no current or planned therapy, and

- have an expected disease-free survival of at least 5 years from study entry

- Chronic use of: itraconazole; ketoconazole; erythromycin; clarithromycin;
telithromycin; human immunodeficiency virus (HIV) protease inhibitors; nefazodone;
cyclosporine; gemfibrozil and other fibrates; danazol; amiodarone (amiodarone
hydrochloride); verapamil; coumarin anticoagulants; niacin (nicotinic acid) (>= 1
g/day); or large quantities of grapefruit juice (> l quart daily)

- Subjects with a history of coronary artery disease or stroke

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Outcome Measure:

Histopathologic regression of target atypical nevi with treatment

Outcome Description:

The level of atypia will be graded in a standard fashion which leads to seven levels of atypia, with zero being no atypia and six being a melanoma. The Wilcoxon rank sum test will be used to compare the changes from baseline in histopathologic score after treatment in both patient groups.

Outcome Time Frame:

From baseline up to 24 weeks

Safety Issue:


Principal Investigator

Kenneth Linden

Investigator Role:

Principal Investigator

Investigator Affiliation:

Chao Family Comprehensive Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

December 2006

Completion Date:

Related Keywords:

  • Precancerous Condition
  • Stage 0 Melanoma
  • Stage I Melanoma
  • Stage II Melanoma
  • Melanoma
  • Precancerous Conditions



H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida  33612
University of California Medical Center At Irvine-Orange Campus Orange, California  92868