Topical Diclofenac and Topical DFMO Chemoprevention Trial in Subjects With a History of Skin Cancer

• Status: Recruiting
• Trial end date: 2022-03-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a single institution, randomized, placebo-controlled, double-blind phase IIB trial of 1) topical diclofenac and topical DFMO, or 2) placebo in participants with a history of non melanoma skin cancer/ keratinocytic cancers.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Alabama at Birmingham
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH)
• Treatments: Diclofenac; Eflornithine

Criteria

Inclusion Criteria:

• · Previous treatment for basal or squamous cell skin cancer stage 0-2 and current evidence of actinic keratosis on the upper extremities (upper arms, forearms and hands), neck, face or scalp.

• Ability to understand and willingness to sign a written informed consent document

• ECOG performance status 0-1

• Willing and able to participate for the full duration of the study

• Greater than 4 weeks from:

• Prior major surgery for any indication

• Prior chemotherapy, hormonal therapy or radiation therapy for cancer

• Willing to abstain from:

• The application of topical medications including prescription and over the counter preparations (e.g. Topical preparations containing corticosteroids or vitamin A derivatives) to areas of actinic damage for the duration of the study. Use of moisturizers/emollients and sunscreens on these areas is allowed.

• Chronic (defined as > 3 times/week for more than 2 consecutive weeks/year) NSAID and COX-2 inhibitor use (other than cardioprotective doses of aspirin < 100 mg po QD) for the duration of the study. For routine analgesia, subjects may take acetaminophen as necessary.

• Normal organ and marrow function defined as laboratory values falling within the specified ranges for the following tests (performed within 31 days of registration)

• Hematologic

• WBC >3,000/ul

• Hemoglobin > lower limit of normal

• Platelet count > 100,000/ul

• Hepatic

• Total bilirubin < 1.5 X ULN

• AST (SGOT) < 1.5 X ULN

• ALT (SPGT) < 1.5 X ULN

• Renal

• Serum creatinine < 1.5 X ULN

• BUN < 1.5 X ULN

• Females of childbearing potential must:

• Have been using adequate contraception (abstinence, IUD, birth control pills or spermicidal gel with diaphragm or condom) since their last menses

• Have a documented negative serum pregnancy test within 14 days prior to the first dose of study medication

FEMALES ARE NOT CONSIDERED TO BE OF CHILDBEARING POTENTIAL IF THEY ARE AT LEAST 1 YEAR POST-MENOPAUSAL OR HAVE HAD A TUBAL LIGATION, BILATERAL OOPHORECTOMY OR HYSTERECTOMY.

· The effects of DFMO and diclofenac on the developing fetus are unknown. Therefore, all females of childbearing potential and all men capable of fathering a child must agree to use adequate contraception (abstinence, IUD, birth control pills, or spermicidal gel with diaphragm or condom) for the duration of study participation.

Exclusion Criteria:

Within 3 months prior to randomization:

• Use of oral or intravenous corticosteroids for more than 2 consecutive weeks

• Use of inhaled corticosteroids for more than 4 consecutive weeks

· Any of the following in the 4 weeks (or as indicated) prior to randomization:

• Major surgery for any indication

• Cytotoxic chemotherapy for any indication (including methotrexate for arthritis)

• Anti-cancer treatment of any type other than for a stage 0-2 non-melanoma skin cancer

• Hormonal therapy for cancer prevention (including tamoxifen) Note: treatment with finasteride/dutasteride for BPH does not render a participant ineligible.

• Radiation therapy

• Topical medications for the treatment of actinic keratosis or skin cancer (etretinate, 5-FU, imiquimod, ingenol) in the 6 months prior to randomization.

• Laser resurfacing, dermabrasion, cryotherapy, chemical peel and electrodissection ± curettage in the 6 months prior to randomization.

• Aspirin (>100 mg/day) - Note: cardioprotective doses (< 100mg/day) are acceptable.

• NSAIDs (other than aspirin < 100mg/day) or COX-2 inhibitors > 3 times/week for more than a two week period

• Topical steroids

• Any personal history of:

• Invasive cancer diagnosed or treated within the past 5 years. Participants who have been in remission for 5 years or more and have not required treatment in the past 5 years may be eligible if a study chair or principal investigator believes there is little to no risk of recurrence.

• Solid organ or bone marrow transplant

• Biopsy proven hepatic cirrhosis

• Keloid formation

• Photosensitivity disorder

• Hypersensitivity or adverse reactions to nonsteroidal anti-inflammatory agents

• Oral DFMO for > 1 month on a prior study

• Any disease that predisposes to NMSC

• An immunodeficiency disorder or the use of an immunosuppressive drug

• Any family history of

o Ornithine diaminotransferase deficiency in a first degree relative

• Concurrent use of the following medications or treatments

• Systemic therapy with psoralens, immunotherapy, retinoids, or radiation therapy

• Cytotoxic chemotherapy for any reason (including methotrexate for arthritis)

• Topical or systemic immunosuppressive therapy.

• Females who are pregnant or lactating. Should a woman become pregnant or suspect she is pregnant while she is participating in this study she should notify her study physician immediately.

• Uncontrolled concurrent illness including ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled symptomatic cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements or other underlying serious medical condition which, in the investigator's opinion might preclude study participation.