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

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ClinicalTrials.gov Identifier: NCT04091022
Recruitment Status : Not yet recruiting
First Posted : September 16, 2019
Last Update Posted : September 17, 2019
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Craig Elmets, University of Alabama at Birmingham

Tracking Information
First Submitted Date  ICMJE September 4, 2019
First Posted Date  ICMJE September 16, 2019
Last Update Posted Date September 17, 2019
Estimated Study Start Date  ICMJE December 1, 2019
Estimated Primary Completion Date March 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 12, 2019)
Change in incidence of non-melanoma skin cancer [ Time Frame: one year ]
The purpose of the study is to determine whether participants randomized to a combination of two FDA approved topical medications topical diclofenac and topical DFMO have a significant change in incidence of (≥ 50% change, p ≤ 0.05) non-melanoma skin cancers (NMSC) than participants randomized to placebo as assessed by clinical and histopathological evaluation.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT04091022 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2019)
  • Safety assessment [ Time Frame: one year ]
    Determination of safety of the combination of topical diclofenac and topical DFMO as compared to placebo using the NCI- Common Terminology Criteria for Adverse Events (CTCAE)
  • Biomarker assessment [ Time Frame: one year ]
    To assess the effect of topical diclofenac and topical DFMO on the following biomarkers in biopsied non-sun exposed skin, skin tissue that has chronic sun damage, and in actinic keratosis skin lesions at 0 and 9 months: mRNA expression of Sonic Hedgehog, Hip1, Ptch1, Gli1, Gli2, Gli3, and p53, Prostaglandin E2, Proliferation indices (PCNA, cyclin D1), Apoptosis markers (Tunel staining, Bcl-2, caspase-3), Polyamine concentrations (putrescine, spermidine, spermine)
  • Biomarker assessment of NMSC [ Time Frame: one year ]
    Effect of topical diclofenac and topical DFMO on biomarkers of squamous cell skin cancer and basal cell skin cancer which include mRNA expression of p53,proliferation indices (PCNA, cyclin D1),apoptosis markers (Tunel staining, Bcl-2, caspase-3), andmarkers of epithelial adhesion (E-cadherin)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Topical Diclofenac and Topical DFMO Chemoprevention Trial in Subjects With a History of Skin Cancer
Official Title  ICMJE A Randomized, Placebo-controlled, Double-blind, Phase II Chemoprevention Clinical Trial of Topical Diclofenac and DFMO in Subjects With a History of Skin Cancer
Brief 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.
Detailed Description

There will be two groups to the study. Individuals, aged 18 years or older, who have extensive actinic damage, at least 8 AKs and a history of at least one non-melanoma skin cancer, but are in otherwise general good health, will be given topical diclofenac and topical DFMO. They will be compared to individuals, aged 18 years or older, who have extensive actinic damage, but are in otherwise general good health, will be given placebo. All participants must be at increased risk of non-melanoma skin cancer as evidenced by a history of prior squamous or basal cell skin cancer, ongoing or history of actinic keratoses, and the presence, at baseline, of at least eight actinic keratoses on the face, neck, scalp and arms. Subjects will be randomized to:

  1. topical diclofenac twice daily and topical DFMO daily
  2. placebo for the topical diclofenac BID and placebo for the topical DFMO daily
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
randomized, placebo-controlled, double-blind
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

This trial will be double-blinded. The clinical team and patient will remain blinded to the randomization.

All study drug will be blinded except to the pharmacists. Records will be kept to document receipt, distribution and disposition of the drugs. Unblinding will only be done at the end of the study or as medically indicated with consent of the study PI and the biostatistician, after consulting the NIH Project Officer.

Primary Purpose: Treatment
Condition  ICMJE Non-melanoma Skin Cancer
Intervention  ICMJE Drug: Solaraze and Vaniqa
Solaraze-topical diclofenac 3% and Vaniqa-topical eflornithine hydrochloride Cream, 13.9% applied to bilateral arms for one year
Other Name: Solaraze-topical diclofenac 3% and Vaniqa-topical eflornithine hydrochloride Cream, 13.9%
Study Arms  ICMJE
  • Active Comparator: Diclofenac + DFMO
    Participants in this arm will apply topical diclofenac to bilateral forearms twice per day and topical DFMO to bilateral forearms once per day.
    Intervention: Drug: Solaraze and Vaniqa
  • Placebo Comparator: Placebo + placebo
    Participants in this arm will apply placebo for topical diclofenac to bilateral forearms twice per day and placebo for topical DFMO to bilateral forearms once per day.
    Intervention: Drug: Solaraze and Vaniqa
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: September 12, 2019)
144
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 1, 2022
Estimated Primary Completion Date March 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Leah Saag, CRNP 205-996-6589 lsaag@uabmc.edu
Contact: Craig Elmets, MD 205-934-5188 celmets@uabmc.edu
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04091022
Other Study ID Numbers  ICMJE pending new
R01CA193885 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Craig Elmets, University of Alabama at Birmingham
Study Sponsor  ICMJE University of Alabama at Birmingham
Collaborators  ICMJE
  • National Institutes of Health (NIH)
  • National Cancer Institute (NCI)
Investigators  ICMJE Not Provided
PRS Account University of Alabama at Birmingham
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP