Skin Cancer Prevention With Nicotinamide in Transplant Recipients – Pilot Trial

Overview

A common long-term side effect of anti-rejection (immunosuppressant) medications is skin cancer. This pilot clinical trial evaluates the feasibility of conducting a larger pivotal trial to examine the efficacy and safety of nicotinamide for prevention of keratinocyte carcinoma in solid organ transplant recipients. This pilot trial will transition into the pivotal trial if all feasibility targets are met.

Full Title of Study: “Nicotinamide Chemoprevention for Keratinocyte Carcinoma in Solid Organ Transplant Recipients: A Pilot, Placebo-controlled, Randomized Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: December 2020

Interventions

  • Drug: Nicotinamide
    • Oral nicotinamide (500 mg) twice daily for at least 52 weeks
  • Drug: Placebo oral capsule
    • Matching placebo taken twice daily for at least 52 weeks

Arms, Groups and Cohorts

  • Experimental: Nicotinamide
  • Placebo Comparator: Placebo

Clinical Trial Outcome Measures

Primary Measures

  • Feasibility (pertaining to patient recruitment)
    • Time Frame: 1 year
    • Proportion of patients who consent to data linkage to provincial administrative databases
  • Feasibility (pertaining to appropriateness of eligibility criteria)
    • Time Frame: 1 year
    • Reasons for exclusion of screened patients
  • Feasibility (pertaining to adherence to intervention)
    • Time Frame: 1 year
    • Proportion of capsules returned, reasons for non-adherence
  • Feasibility (pertaining to adherence to follow-up assessments)
    • Time Frame: 1 year
    • Proportion of missed assessments and incomplete questionnaire data variables, proportion of patients who withdraw from the trial, patient perception of trial participation
  • Feasibility (pertaining to data linkage)
    • Time Frame: 1 year
    • Proportion of patients who consent to data linkage to provincial administrative databases
  • Preliminary pooled keratinocyte carcinoma event rate
    • Time Frame: 1 year
    • Pooled keratinocyte carcinoma event rate to be used for sample size re-estimation in the pivotal trial.
  • Drug interactions
    • Time Frame: 1 week
    • Proportion of patients with a clinically relevant increase in cyclosporine or tacrolimus blood concentration at 1 week. An increased level will be classified as clinically relevant if the transplant physician reduces the immunosuppressant dose in response to the increased drug level.
  • Drug interactions
    • Time Frame: 2 weeks
    • Proportion of patients with a clinically relevant increase in cyclosporine or tacrolimus blood concentration at 2 weeks. This measurement will be dropped if all cases of clinically relevant drug interactions manifest at 1 week in the first 20 enrolled participants.
  • Serious adverse events
    • Time Frame: 1 year
    • Descriptive tabulation (preliminary safety)

Secondary Measures

  • Feasibility of recruiting for neurocognitive substudy
    • Time Frame: 1 year
    • Proportion of enrolled participants who consent to participate in the neurocognitive substudy
  • Baseline prevalence of cognitive impairment (substudy)
    • Time Frame: 1 year
    • Montreal Cognitive Assessment (MoCA) score <26, scored out of 30.
  • Pooled standard deviation of MoCA test scores (substudy)
    • Time Frame: 1 year
    • Montreal Cognitive Assessment (MoCA), raw scores are scored out of 30, with a higher score representing better cognitive function
  • Pooled standard deviation of Hopkins Verbal Learning Test – Revised scores (substudy)
    • Time Frame: 1 year
    • Hopkins Verbal Learning Test – Revised, a memory test scored out of 60, with a higher score representing better memory
  • Pooled standard deviation of Trail Making A and B test scores (substudy)
    • Time Frame: 1 year
    • Trail Making A and B, a visual attention test. This records the time (in seconds) to completion, with a faster time representing better cognitive function
  • Pooled standard deviation of Controlled Oral Word Association test scores (substudy)
    • Time Frame: 1 year
    • Controlled Oral Word Association, a verbal fluency test, measures the production of words belonging to the same letter. This records total number of words produced, with a higher number representing better verbal fluency.
  • Pooled standard deviation of Animal Naming Task scores (substudy)
    • Time Frame: 1 year
    • Animal Naming Task, a verbal fluency task, measures the total number of animals named in one minute, with a higher number representing better verbal fluency
  • Pooled standard deviation of cognitive test scores (substudy)
    • Time Frame: 1 year
    • Wechsler Adult Intelligence Scale – Revised, Digit Span subtest, a number sequencing memory test, measures the number of correctly repeated sequences with maximum score of 48. The higher score represents better cognitive function
  • Pooled standard deviation of serum phosphate levels (substudy)
    • Time Frame: 1 year

Participating in This Clinical Trial

Inclusion Criteria

1. Age ≥ 18 years old 2. Kidney, liver, heart, or lung transplant at least two years ago 3. History of at least one prior histologically-confirmed keratinocyte carcinoma or squamous cell carcinoma in situ 4. Currently immunosuppressed with a calcineurin inhibitor-based regimen (cyclosporine or tacrolimus) 5. Able to attend follow-up visits 6. Able to speak and understand English (only for cognitive substudy) Exclusion Criteria:

1. Use of mTOR inhibitor (sirolimus, everolimus) within the past 12 weeks 2. Biopsy-confirmed acute rejection episode within the past 12 weeks 3. Active liver disease (elevated AST or ALT >3 times normal) 4. Severe renal failure (estimated glomerular filtration rate <20 mL/min/1.73 m2) 5. Current carbamazepine or primidone use 6. Pregnancy and lactation 7. Gorlin syndrome or other genetic skin cancer syndrome 8. Solid organ or hematologic malignancy, invasive Stage II melanoma, Merkel cell carcinoma, or metastatic skin cancer within the past five years, or invasive Stage I melanoma within the past two years 9. Untreated localized skin cancer (invasive squamous cell carcinoma, basal cell carcinoma, or keratoacanthoma) at baseline (the patient can enrol after skin cancer treatment) 10. Use of nicotinamide or niacin within the past 12 weeks 11. Use of field therapy for actinic keratoses within the past 12 weeks 12. Initiation of systemic chemoprevention within the past 12 weeks

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Women’s College Hospital
  • Collaborator
    • Canadian Institutes of Health Research (CIHR)
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • An-Wen Chan, MD DPhil, Principal Investigator, Women’s College Hospital
    • Joseph Kim, MD PhD, Principal Investigator, University Health Network, Toronto
  • Overall Contact(s)
    • Ashley Lau, BMRSc, 416-351-3732, ashley.lau@wchospital.ca

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