Sulindac in Preventing Melanoma in Healthy Participants Who Are at Increased Risk of Melanoma

Phase II Trial of Sulindac in Individuals at Increased Risk for Melanoma

This randomized phase II trial is studying how well sulindac works in preventing melanoma in healthy participants who are at increased risk of melanoma. Sulindac may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether sulindac is more effective than a placebo in preventing melanoma in individuals with many moles and abnormal moles.

Study Overview

• Status: Completed
• Conditions: Precancerous Condition
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: sulindac; Other: placebo

Detailed Description

PRIMARY OBJECTIVE:

I. To determine sulindac and metabolite levels in healthy participants with atypical nevi and benign nevus at increased risk for melanoma treated with sulindac versus placebo.

SECONDARY OBJECTIVES:

I. To assess the effects of sulindac on apoptosis in atypical nevi of these participants.

II. To assess the effects of sulindac on VEGF expression in atypical nevi of these participants.

III. To assess sulindac and metabolite levels in plasma and its association with drug levels in the target tissue.

OUTLINE: This is a multicenter study. Participants are randomized to 1 of 2 treatment arms.

ARM I: Participants receive oral sulindac twice daily.

ARM II: Participants receive oral placebo twice daily.

In both arms, treatment continues for 8 weeks in the absence of unacceptable toxicity.

Blood and tissue samples are collected at baseline and/or after completion of study therapy and analyzed for sulindac and metabolite levels via high performance liquid chromatography tandem mass spectrometry; the detection of apoptotic cells via TUNEL assay; and VEGF expression via immunohistochemistry assays.

After completion of study therapy, participants are followed for 2 weeks.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Health Sciences Center
  • California
    • Stanford, California, United States, 94305
      • Stanford University Hospitals and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Criteria:

• Healthy participants at risk for developing melanoma and meeting the following criteria: must have >= 4 large (>= 5 mm and < 15 mm) atypical nevi and have 1 benign nevus amenable to biopsies
• No histologically confirmed melanoma on the baseline biopsy
• No more than 1 prior cutaneous melanoma
• One prior stage I, IIA, or IIB melanoma allowed provided patients have been off treatment > 3 months
• Modified dermoscopy score < 4.8
• Karnofsky performance status 80-100%
• ANC >= 1,500/mm^3
• No family history of melanoma involving >= 2 first degree relatives
• Platelets count >= 100,000/mm^3
• Total bilirubin =< 2.0 mg/dL
• AST/ALT =< 2.0 times upper limit of normal
• Creatinine =< 1.5 mg/dL
• Not pregnant or nursing
• Fertile patients must use effective contraception
• More than 6 months since prior and no concurrent tanning bed use or other methods to promote sun-tanning
• Willing to minimize sunlight exposure by applying sunscreen/sunblock or wearing clothing to shield skin during outdoor activity during study participation
• Willing or able to limit alcohol consumption to less than 3 servings a week during the study period
• No frequent, chronic or moderate/severe gastrointestinal (GI) complaints
• Upper GI problems requiring prescription or nonprescription medical remedies for symptoms of heartburn, dyspepsia, nausea, or abdominal pain > once a week on average
• History of peptic ulcer, occult or gross intestinal bleeding
• No prior allergic reaction to aspirin (unless subsequent dosing with other NSAIDs has been well tolerated)
• No history of allergic reaction to lidocaine or xylocaine
• No history of allergic reaction (e.g., urticaria, asthma, or rhinitis) or gastric intolerance attributed to compounds of similar chemical or biological composition to sulindac
• No invasive cancer or cancer treatment within the past 5 years, except nonmelanoma skin cancer
• No immunosuppression by medication or disease, including any of the following: AIDS, oral prednisone, immunosuppressant/immunomodulator (i.e., cyclosporine, chemotherapeutic agent, or biologic therapy)
• No uncontrolled intercurrent illness
• No ongoing or active infection
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No psychiatric illness/social situations that would limit compliance with study requirements
• At least 30 days since prior participation and no concurrent enrollment or planning to enroll in another clinical trial
• No NSAIDs for more than 5 days per month within the past 3 months and no concurrent non-study NSAIDs, except low dose aspirin (81 mg/day)
• Willing or able to refrain from herbal medicines, above-standard vitamins, or minerals during study
• Standard daily multivitamin/mineral supplement (i.e., therapeutic doses of calcium and vitamin D for osteoporosis) allowed
• No concurrent lithium, phenytoin, or sulfonamides
• WBC >= 3,000/mm^3
• No history of bleeding or clotting disorder
• At least 3 months since prior and no concurrent coumadin or other systemic anticoagulant other than aspirin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Participants receive oral sulindac twice daily for 8 weeks	Other: laboratory biomarker analysis; Correlative studies; Drug: sulindac; Given orally; Other Names: Aflodac; Algocetil; Clinoril; SULIN
Placebo Comparator: Arm II; Participants receive oral placebo twice daily for 8 weeks	Other: laboratory biomarker analysis; Correlative studies; Other: placebo; Inactive agent; Other Names: PLCB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Sulindac Concentration in the Nevi (Moles)	8 weeks
Sulindac Sulfone, an Active Metabolite of Sulindac, Concentration in the Nevi	8 weeks
Sulindac Sulfide, an Active Metabolite of Sulindac, Concentration in the Nevi	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sulindac Effects on Apoptosis in Atypical Nevi	Change in the expression of a marker of apoptosis, cleaved caspase 3, in melanocytic junctional component	Baseline and 8 weeks
Sulindac Effects on Vascular Endothelial Growth Factor (VEGF) Expression in Atypical Nevi	Change in VEGF expression in melanocytic junctional component	Baseline and 8 weeks
Association Between Plasma and Target Tissue Sulindac Levels		8 weeks
Association Between Plasma and Target Tissue Sulindac Sulfone Levels		8 weeks
Association Between Plasma and Target Tissue Sulindac Sulfide Levels		8 weeks

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: February 10, 2009
• First Submitted That Met QC Criteria: February 10, 2009
• First Posted (Estimate): February 11, 2009

Study Record Updates

• Last Update Posted (Actual): December 26, 2017
• Last Update Submitted That Met QC Criteria: November 30, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Precancerous Conditions; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; Sulindac
• Other Study ID Numbers: NCI-2009-01115 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA023074 (U.S. NIH Grant/Contract); N01CN35158 (U.S. NIH Grant/Contract); UARIZ-08-0841-04; CDR0000633938; 08-0841-04 (Other Identifier: University of Arizona Health Sciences Center); UAZ05-2-10 (Other Identifier: DCP)