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

• ClinicalTrials.gov Identifier: NCT00841204
• Recruitment Status: Completed
• First Posted: February 11, 2009
• Results First Posted: March 16, 2012
• Last Update Posted: December 26, 2017
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Precancerous Condition	Drug: sulindac; Other: placebo; Other: laboratory biomarker analysis	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Phase II Trial of Sulindac in Individuals at Increased Risk for Melanoma
• Study Start Date: February 2009
• Actual Primary Completion Date: February 2011
• Actual Study Completion Date: February 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Sulindac Concentration in the Nevi (Moles) [ Time Frame: 8 weeks ]
2. Sulindac Sulfone, an Active Metabolite of Sulindac, Concentration in the Nevi [ Time Frame: 8 weeks ]
3. Sulindac Sulfide, an Active Metabolite of Sulindac, Concentration in the Nevi [ Time Frame: 8 weeks ]

Secondary Outcome Measures :

1. Sulindac Effects on Apoptosis in Atypical Nevi [ Time Frame: Baseline and 8 weeks ]
   Change in the expression of a marker of apoptosis, cleaved caspase 3, in melanocytic junctional component
2. Sulindac Effects on Vascular Endothelial Growth Factor (VEGF) Expression in Atypical Nevi [ Time Frame: Baseline and 8 weeks ]
   Change in VEGF expression in melanocytic junctional component
3. Association Between Plasma and Target Tissue Sulindac Levels [ Time Frame: 8 weeks ]
4. Association Between Plasma and Target Tissue Sulindac Sulfone Levels [ Time Frame: 8 weeks ]
5. Association Between Plasma and Target Tissue Sulindac Sulfide Levels [ Time Frame: 8 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, Arizona

University of Arizona Health Sciences Center

Tucson, Arizona, United States, 85724

United States, California

Stanford University Hospitals and Clinics

Stanford, California, United States, 94305

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Hsiao-Hui (Sherry) Chow; University of Arizona Health Sciences Center

More Information

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00841204
• Other Study ID Numbers: NCI-2009-01115; NCI-2009-01115 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); UARIZ-08-0841-04; CDR0000633938; N01CN35158 ( U.S. NIH Grant/Contract ); 08-0841-04 ( Other Identifier: University of Arizona Health Sciences Center ); UAZ05-2-10 ( Other Identifier: DCP ); P30CA023074 ( U.S. NIH Grant/Contract )
• First Posted: February 11, 2009
• Results First Posted: March 16, 2012
• Last Update Posted: December 26, 2017
• Last Verified: November 2017

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; Sulindac; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action