Lovastatin in Treating Patients At High Risk of Melanoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00462280
First received: April 18, 2007
Last updated: December 6, 2013
Last verified: December 2013
  Purpose

The use of lovastatin may slow disease progression in patients at high risk of melanoma. It is not yet known whether lovastatin is more effective than a placebo in treating patients at high risk of melanoma. This randomized phase II trial studies how well giving lovastatin or placebo works in treating patients at high risk of melanoma.


Condition Intervention Phase
Precancerous Condition
Stage 0 Melanoma
Stage I Melanoma
Stage II Melanoma
Drug: lovastatin
Other: placebo
Procedure: biopsy
Procedure: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial of Lovastatin for Various Endpoints of Melanoma Pathobiology

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Histopathologic regression of target atypical nevi with treatment [ Time Frame: From baseline up to 24 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Total nevus number on patient's back [ Time Frame: From baseline up to 24 weeks ] [ Designated as safety issue: No ]
    Assessed by photos of subjects' back pre and post treatment. These photos will be used to count, by blinded evaluators, the number of nevi on the back pre and post therapy.

  • Serum and molecular biomarkers [ Time Frame: From baseline up to 24 weeks ] [ Designated as safety issue: No ]
    Biomarkers vascular endothelial growth factor (VEGF) and Ki-67 and serum components cyclin-dependent kinase inhibitor 1A (p21) and RelA along with expression of epithelial (e)-cadherin and neural (n)-cadherin will be analyzed.

  • Clinical regression of atypical moles [ Time Frame: From baseline up to 24 weeks ] [ Designated as safety issue: No ]
    From close-up photos of target atypical nevi, lesions will be graded clinically and classified into one of three categories: (1) decrease in clinical atypia, (2) no change, or (3) increase in clinical atypia over the course of the trial. The Wilcoxon rank sum test for ordered categories will be applied to compare the tricotomized change scores for patients treated with placebo vs. those treated with lovastatin. The null hypothesis is that, after treatment, the distribution of changes from baseline is the same for both placebo- and lovastatin-treated patient.

  • Incidence of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 [ Time Frame: Baseline up to 26 weeks ] [ Designated as safety issue: Yes ]
    All participants will be evaluable for toxicity from the time of their informed consent.


Estimated Enrollment: 120
Study Start Date: May 2007
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (lovastatin)
Patients receive lovastatin PO QD for up to 6 months in the absence of disease progression or unacceptable toxicity.
Drug: lovastatin
Given PO
Other Names:
  • Lovastatin Sodium
  • Mevacor
  • Mevinolin
  • Monacolin K
Procedure: biopsy
Correlative studies
Other Name: biopsies
Procedure: laboratory biomarker analysis
Correlative studies
Placebo Comparator: Arm II (placebo)
Patients receive placebo PO QD for up to 6 months in the absence of disease progression or unacceptable toxicity.
Other: placebo
Given PO
Other Name: PLCB
Procedure: biopsy
Correlative studies
Other Name: biopsies
Procedure: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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), she:

    • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00462280

Locations
United States, California
University of California Medical Center At Irvine-Orange Campus
Orange, California, United States, 92868
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
Investigators
Principal Investigator: Kenneth Linden Chao Family Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00462280     History of Changes
Other Study ID Numbers: NCI-2009-00896, NCI-2009-00896, 2006-4937, UCI03-1-01, CDR0000540141, UCI 06-06, UCI03-1-01, N01CN35160
Study First Received: April 18, 2007
Last Updated: December 6, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Melanoma
Precancerous Conditions
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Lovastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014