Lovastatin in Treating Patients At High Risk of Melanoma

NCT00462280 | Completed Phase 2 Results DMC

• 6 other identifiers: NCI-2009-008962006-4937UCI03-1-01CDR0000540141UCI 06-06N01CN35160
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Precancerous Condition; Stage 0 Melanoma; Stage I Melanoma; Stage II Melanoma

Outcome Measures

Primary Outcomes (2)

• Histopathologic Regression of Target Atypical Nevi With Treatment - Pathologist 1's Evaluation

  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. For each patient, the change from baseline in the level of atypia was calculated. Only the Two Matched Nevi Group - Lovastatin and Two Matched Nevi Group - Placebo data were used and analyzed for the primary outcome. One-Large Nevi Group - Lovastatin and One-Large Nevi Group - Placebo sample data were not used or analyzed due to insufficient numbers.

  From baseline up to 24 weeks

• Histopathologic Regression of Target Atypical Nevi With Treatment - Pathologist 2's Evaluation

  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. For each patient, the change from baseline in the level of atypia was calculated. Only the Two Matched Nevi Group - Lovastatin and Two Matched Nevi Group - Placebo data were used and analyzed for the primary outcome. One-Large Nevi Group - Lovastatin and One-Large Nevi Group - Placebo sample data were not used or analyzed due to insufficient numbers.

  From baseline up to 24 weeks

Secondary Outcomes (25)

• Clinical Regression of Atypical Moles - Average of Three Reviewers' Evaluations

  From baseline up to 24 weeks

• Total Nevus Number on Patient's Back - Combined Three Reviewers' Evaluations

  From baseline up to 24 weeks

• Serum and Molecular Biomarkers - HIF1alpha: Pathologist 3's Evaluation

  From baseline up to 24 weeks

• Serum and Molecular Biomarkers - (e)-Cadherin: Pathologist 3's Evaluation

  From baseline up to 24 weeks

• Serum and Molecular Biomarkers - (n)-Cadherin: Pathologist 3's Evaluation

  From baseline up to 24 weeks

Study Arms (4)

Two matched nevi group - Lovastatin

EXPERIMENTAL

Patients with two matched nevi received lovastatin PO QD for up to 6 months in the absence of disease progression or unacceptable toxicity.

Drug: lovastatin; Procedure: biopsy; Procedure: laboratory biomarker analysis

Two Matched Nevi Group - Placebo

PLACEBO COMPARATOR

Patients with two matched nevi received placebo PO QD for up to 6 months in the absence of disease progression or unacceptable toxicity

Other: placebo; Procedure: biopsy; Procedure: laboratory biomarker analysis

One large nevi group - Lovastatin

EXPERIMENTAL

Patients who have one large nevi received lovastatin PO QD for up to 6 months in the absence of disease progression or unacceptable toxicity

Drug: lovastatin; Procedure: biopsy; Procedure: laboratory biomarker analysis

One Large Nevi Group - Placebo

PLACEBO COMPARATOR

Patients who have one large nevi received placebo PO QD for up to 6 months in the absence of disease progression or unacceptable toxicity

Other: placebo; Procedure: biopsy; Procedure: laboratory biomarker analysis

Interventions

lovastatin DRUG

Given PO

Also known as: Lovastatin Sodium, Mevacor, Mevinolin, Monacolin K

One large nevi group - Lovastatin; Two matched nevi group - Lovastatin

placebo OTHER

Given PO

Also known as: PLCB

One Large Nevi Group - Placebo; Two Matched Nevi Group - Placebo

biopsy PROCEDURE

Correlative studies

Also known as: biopsies

One Large Nevi Group - Placebo; One large nevi group - Lovastatin; Two Matched Nevi Group - Placebo; Two matched nevi group - Lovastatin

laboratory biomarker analysis PROCEDURE

Correlative studies

One Large Nevi Group - Placebo; One large nevi group - Lovastatin; Two Matched Nevi Group - Placebo; Two matched nevi group - Lovastatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

University of California Medical Center At Irvine-Orange Campus

Orange, California, 92868, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Precancerous Conditions; Melanoma

Interventions

Lovastatin; Biopsy

Condition Hierarchy (Ancestors)

Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Dr. Kenneth G. Linden
• Organization: University of California, Irvine

kglinden@uci.edu

714-456-3719

Study Officials

• Kenneth Linden

  Chao Family Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2007
• First Posted: April 19, 2007
• Study Start: May 1, 2007
• Primary Completion: April 1, 2011
• Study Completion: February 1, 2012
• Last Updated: October 31, 2014
• Results First Posted: October 31, 2014

Record last verified: 2014-02

Locations

US (3)