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

Condition(s) targeted: Precancerous/Nonmalignant Condition

Intervention: sulindac (Drug); placebo (Other)

Phase: Phase 2

Status: Recruiting

Sponsored by: University of Arizona

Official(s) and/or principal investigator(s):
H. H. Sherry Chow, PhD, Study Chair, Affiliation: University of Arizona
Clara Curiel, MD, Affiliation: University of Arizona

RATIONALE: 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.

PURPOSE: This randomized phase II trial is studying how well sulindac works in preventing melanoma in healthy participants who are at increased risk of melanoma.

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

Study design: Treatment, Randomized, Double-Blind, Placebo Control

Primary outcome: Bioavailability of sulindac and its metabolite in target tissue as measured by post-intervention nevus sulindac and sulindac metabolite concentrations

Secondary outcome:

Sulindac effects on apoptosis in atypical nevi

Sulindac effects on VEGF expression in atypical nevi

Association between plasma and target tissue drug levels

Detailed description: OBJECTIVES:

Primary

- 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

- Assess the effects of sulindac on apoptosis in atypical nevi of these participants.

- Assess the effects of sulindac on VEGF expression in atypical nevi of these

participants.

- 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.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Healthy participants at risk for developing melanoma and meeting the following

criteria:

- Must have ≥ 4 large (≥ 5 mm and < 15 mm) atypical nevi

- Must 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

- No family history of melanoma involving ≥ 2 first degree relatives

- Modified dermoscopy score < 4. 8

PATIENT CHARACTERISTICS:

- Karnofsky performance status 80-100%

- WBC ≥ 3,000/mm³

- ANC ≥ 1,500/mm³

- Platelets count ≥ 100,000/mm³

- 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 including,

but not limited to, any of the following:

- 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 history of bleeding or clotting disorder

- 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 including, but not limited to, any of the

following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness/social situations that would limit compliance with study

requirements

PRIOR CONCURRENT THERAPY:

- At least 3 months since prior and no concurrent coumadin or other systemic

anticoagulant other than aspirin

- 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

Arizona Cancer Center at University of Arizona Health Sciences Center, Tucson, Arizona 85724-5024, United States; Recruiting
Clinical Trials Office - Arizona Cancer Center at University o, Phone: 520-626-9008

Stanford Cancer Center, Stanford, California 94305-5824, United States; Recruiting
Clinical Trials Office - Stanford Cancer Center, Phone: 650-498-7061, Email: cctoffice@stanford.edu

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: February 2009
Last updated: June 9, 2009