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Trial registered on ANZCTR


Registration number
ACTRN12612000625875
Ethics application status
Approved
Date submitted
6/06/2012
Date registered
12/06/2012
Date last updated
1/03/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
ONTRAC: Effect of oral nicotinamide (vitamin B3) on incidence of nonmelanoma skin cancer and actinic keratoses: a randomised controlled trial (Oral Nicotinamide To Reduce Actinic Cancer)
Scientific title
Randomised double blinded placebo controlled trial to assess the effect of oral nicotinamide on numbers of new nonmelanoma skin cancers in immune competent adult patients with a history of at least two histologically confirmed nonmelanoma skin cancers within the previous five years
Secondary ID [1] 280600 0
Nil
Universal Trial Number (UTN)
U1111-1131-4069
Trial acronym
ONTRAC (Oral Nicotinamide To Reduce Actinic Cancer)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Nonmelanoma skin cancer 286605 0
Actinic keratoses 286606 0
Basal cell carcinoma 286607 0
Cutaneous squamous cell carcinoma 286608 0
Cognitive function 286609 0
Transepidermal water loss 286610 0
Condition category
Condition code
Cancer 286881 286881 0 0
Non melanoma skin cancer
Neurological 286882 286882 0 0
Studies of the normal brain and nervous system
Skin 286883 286883 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral nicotinamide 500mg orally twice daily for 12 months
Intervention code [1] 284990 0
Prevention
Intervention code [2] 284991 0
Treatment: Drugs
Comparator / control treatment
Placebo tablet containing calcium hydrogen phosphate anhydrous and cellulose- microcrystalline; taken orally twice daily for 12 months
Control group
Placebo

Outcomes
Primary outcome [1] 287238 0
Number of nonmelanoma skin cancers (basal cell carcinomas + cutaneous squamous cell carcinomas + cutaneous squamous cell carcinomas in situ + keratoacanthomas) as assessed by histological examination of lesions detected during dermatological follow up
Timepoint [1] 287238 0
A 12 months after randomisation
Secondary outcome [1] 297703 0
Numbers of actinic keratoses assessed by clinical counting
Timepoint [1] 297703 0
At 0, 3, 6, 9 and 12 months after randomisation
Secondary outcome [2] 297704 0
Numbers of nonmelanoma skin cancers confirmed by histology
Timepoint [2] 297704 0
At 3, 6, 9, 15 and 18 months after randomisation
Secondary outcome [3] 297705 0
Numbers of basal cell carcinomas confirmed by histology
Timepoint [3] 297705 0
At 3, 6, 9, 12, 15 and 18 months after randomisation
Secondary outcome [4] 297706 0
Numbers of cutaneous squamous cell carcinomas (including squamous cell carcinomas in situ and keratoacanthomas) confirmed by histology
Timepoint [4] 297706 0
At 3, 6, 9, 12, 15 and 18 months after randomisation
Secondary outcome [5] 297707 0
Skin cancer recurrences, occurring at sites of previously histologically confirmed skin cancer, assessed by histology
Timepoint [5] 297707 0
Skin cancers recurring at any timepoint during the 18 month study period
Secondary outcome [6] 297708 0
Skin tumour markers of skin cancer proliferation, differentiation, apoptosis, immune cell infiltration and DNA damage assessed with immunohistochemistry; SCC differentiation and BCC subtype assessed by histology
Timepoint [6] 297708 0
On skin cancers developing at any timepoint during the 12 month intervention period of the study
Secondary outcome [7] 297709 0
Change in cognitive function assessed with standardised neuropsychological tests in the cognitive domains of memory, concentration, attention and executive function

-Hopkins Verbal Learning Test Revised (HVLT-R) (Brandt, 1991).

-Controlled Oral Word Association (COWA) (Spreen et al, 1998).

-Stroop Color and Word Test (Spreen and Strauss, 1998).

-Trail Making A & B (Reitan, 1955).
Timepoint [7] 297709 0
At baseline and 12 months after randomisation
Secondary outcome [8] 297742 0
Change in self-reported quality of life, assessed by:

-EORTC QLQ-C30 Cognitive Function items, PROMIS cognitive abilities item pool, cognitive general concerns item pool
-PROMIS fatigue item pool
-PROMIS anxiety item pool
-PROMIS depression item pool
-PROMIS Global Health Short Form for global health perception
Timepoint [8] 297742 0
At baseline and 12 months after randomisation
Secondary outcome [9] 297819 0
Transepidermal water loss assessed with Delfin Vapometer (assessed in RPAH study site participants only)
Timepoint [9] 297819 0
At 0, 3, 6, 9 and 12 months after randomisation

Eligibility
Key inclusion criteria
Aged 18 years or older with at least two histologically confirmed nonmelanoma skin cancers with the previous 5 years
Equivalent to Year 8 spoken and written English skills to participate in the cognitive component of the study.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Immune suppression (due to current immune suppressive medication, or immune suppressive medical condition such as haematological malignancy, HIV infection, congenital immune deficiency)
2. Severe liver disease (transaminases >3x normal)
3. Active peptic ulcer disease
4. Recent myocardial infarction
5. Hypotension
6. Renal impairment with eGFR < 30 mL/min/1.73 m2
7. Internal malignancy, metastatic SCC or invasive melanoma within the past 5 years.
8. Need for ongoing carbamazepine use (possible interaction with nicotinamide).
9. Patients unavailable for follow up for the duration of the study because of general frailty, geographical or social reasons.
10. Gorlin’s syndrome or other genetic skin cancer syndrome.
11. Huge numbers of current skin cancers or large areas of confluent skin cancer at baseline preventing accurate assessment and counting of new skin cancers.
12. Pregnancy or lactation (any women of childbearing potential will be required to use contraception throughout the study).
13. Patients taking acitretin or other oral retinoids within the past 6 months
14. Taking supplemental nicotinamide or niacin (other nicotinamide supplements to be ceased 4 weeks prior to study commencement).
15. Field treatment for AKs (topical use of 5 fluorouracil, imiquimod, diclofenac, retinoids; topical photodynamic therapy for AKs; laser resurfacing or chemical peel treatments for AKs) within the previous 4 weeks.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All eligible patients enrolled on the study by will be entered into the central randomisation system.
The patient number assigned at the time of randomisation will be the primary identifier for the patient. Randomisation will be performed by the NHMRC Clinical Trials Centre which will provide a centralised tele-randomisation service that will randomly allocate patients to nicotinamide or placebo groups in a 1:1 ratio stratified by baseline skin cancer count, gender and study site. The pharmacist will provide the drug kit allocated by the system for the patient, recording the kit number in the pharmacy log. The study number, patient name and MRN should then be written on the medication bottle.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised to nicotinamide or placebo groups in a 1:1 ratio using a permuted blocks method stratified by baseline skin cancer count (6 or more versus 2-5 previous nonmelanoma skin cancers), gender and study site.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment postcode(s) [1] 5387 0
2050
Recruitment postcode(s) [2] 5386 0
2145

Funding & Sponsors
Funding source category [1] 285359 0
Government body
Name [1] 285359 0
National Health and Medical Research Council
Address [1] 285359 0
Level 1
16 Marcus Clarke Street
Canberra ACT 2601
Country [1] 285359 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
Sydney Medical School, University of Sydney, NSW 2006
Country
Australia
Secondary sponsor category [1] 284214 0
None
Name [1] 284214 0
Address [1] 284214 0
Country [1] 284214 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287374 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 287374 0
Research Development Office
Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Ethics committee country [1] 287374 0
Australia
Date submitted for ethics approval [1] 287374 0
Approval date [1] 287374 0
08/11/2011
Ethics approval number [1] 287374 0
HREC/11/RPAH/506

Summary
Brief summary
This study aims to assess the effect of nicotinamide (vitamin B3) on incidence of nonmelanoma skin cancer and actinic keratoses. Who is it for? You may be eligible to join this study if you are aged 18 years or more and have had at least two confirmed nonmelanoma skin cancers within the previous 5 years. Trial details Participants in this trial will be randomly (by chance) allocated to one of two groups. Participants in one group will take two 500mg nicotinamide (vitamin B3) tablets daily for 12 months, whilst those in the other group will take two placebo (inactive) tablets daily instead. Participants will not know which group they are in until the end of the trial. Participants will be regularly assessed over the treatment period and for 6 months after the treatment period to determine the efficacy of nicotinamide in preventing nonmelanoma skin cancer.
Trial website
Trial related presentations / publications
Chen AC, Martin AJ, Choy B, Fernandez-Penas P, Dalziell RA, McKenzie CA, Scolyer RA, Dhillon HM, Vardy JL, Kricker A, St George G, Chinniah N, Halliday GM, Damian DL. A Phase 3 Randomized Trial of Nicotinamide for Skin Cancer Chemoprevention. New England Journal of Medicine 373 (17), 1618-1626, 2015
Public notes

Contacts
Principal investigator
Name 34250 0
Prof Diona Damian
Address 34250 0
Dermatology, GH3 Royal Prince Alfred Hospital Missenden Rd Camperdown NSW 2050
Country 34250 0
Australia
Phone 34250 0
+612 95158295
Fax 34250 0
+612 9565 1048
Email 34250 0
diona.damian@sswahs.nsw.gov.au
Contact person for public queries
Name 17497 0
Prof Professor Diona Damian
Address 17497 0
Dermatology, GH3
Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Country 17497 0
Australia
Phone 17497 0
+612 95158295
Fax 17497 0
+612 9565 1048
Email 17497 0
diona.damian@sswahs.nsw.gov.au
Contact person for scientific queries
Name 8425 0
Prof Professor Diona Damian
Address 8425 0
Dermatology, GH3
Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Country 8425 0
Australia
Phone 8425 0
+612 95158295
Fax 8425 0
+612 9565 1048
Email 8425 0
diona.damian@sswahs.nsw.gov.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary