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Trial registered on ANZCTR


Registration number
ACTRN12621000092897
Ethics application status
Approved
Date submitted
22/10/2020
Date registered
1/02/2021
Date last updated
1/02/2021
Date data sharing statement initially provided
1/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
THE SCRIPT (Snp Cancer Risk Prediction) TRIAL: A STUDY OF DNA TESTING TO TAILOR BOWEL CANCER SCREENING IN PRIMARY CARE
Scientific title
The SCRIPT (Snp Cancer Risk Prediction): an RCT on the effect of a genomic risk score delivered in primary care on risk-appropriate colorectal cancer screening
Secondary ID [1] 302589 0
Application ID: 1183338
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bowel cancer 319472 0
Bowel cancer screening 319473 0
Condition category
Condition code
Cancer 317439 317439 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The SCRIPT intervention is a ‘complex intervention’, that is, it contains several components. The main component is a polygenic risk score, with a post-test consultation to discuss the participant's personal risk with an associated risk reports for the participant and their GP. The reports are designed to alter screening and referral behaviours.

Participants (recruited from general practice) will attend a consultation, delivered by a trained researcher, during which their family history of colorectal cancer will be obtained, and brief pre-test counselling about the colorectal cancer polygenic risk score. This will include information about the test and its potential implications, including recommendations about colorectal cancer screening. A DNA sample will be obtained using the cheek swab at the first consultation.

A polygenic risk score will be generated from the presence or absence of each of the 45 SNPs, using the relative risk of colorectal cancer for each DNA variant and also the individual’s family history of colorectal cancer. Applying Australian age-sex incidence data, a 10-year absolute risk of colorectal cancer will be calculated. Screening recommendations (faecal occult blood test (FOBT) or colonoscopy) will be generated in accordance with the 2017 NHMRC-endorsed national guidelines which are based on 10-year absolute risks of colorectal cancer. For those with a 10-year risk <1%, the would not require screening; for those with a 10-year risk >1% & <4%, they will be recommended FOBT screening; for those with a 10-year risk >4%, they will be recommended colonoscopic screening; however, no participant will be recommended less screening than the current NHMRC-endorsed national guidelines

Participants in the intervention arm will return two weeks after their pre-test consultation/recruitment to discuss the results of their polygenic risk score with the researcher. A print-out summarising the participant’s colorectal cancer risk and screening recommendations will be given to them to discuss with their GP who will, if required, organise appropriate colorectal cancer screening. The risk report is designed to increase response efficacy for screening (a person’s belief that the behaviour will reduce their disease risk). Those who are due for an FOBT kit will be given a test kit and a brief demonstration on its use to increase their self-efficacy to perform the test. Intervention participants will complete a baseline questionnaire at recruitment and another at 1, 6 and 12 months post recruitment either online or by hardcopy.
Intervention code [1] 318873 0
Early detection / Screening
Intervention code [2] 318874 0
Behaviour
Intervention code [3] 318875 0
Prevention
Comparator / control treatment
Control participants will have a consultation delivered by a trained researcher during which the Cancer Council Victoria 2018 ‘Cut your cancer risk’ brochure will be discussed, and a hard copy provided. This covers generic information including lifestyle changes and brief information about the three national cancer screening programs. The focus of the consultation will be about lifestyle factors to reduce cancer risk. This is designed as a credible ‘attention control’ while not altering ‘usual care’ since it is unlikely to prompt discussions about colorectal cancer risk or screening with their GP. It also increases engagement in the trial for control participants to minimise attrition.
Control participants will complete the same questionnaires as the intervention group at baseline/recruitment then 1, 6 and 12 months post recruitment.
Participants are not blinded.
The Control group will receive the DNA test results report after the 12 month intervention period from the time of recruitment/DNA test.
Control group
Active

Outcomes
Primary outcome [1] 325478 0
To measure the effect of offering a polygenic risk score for colorectal cancer risk and tailored advice (i.e. the SCRIPT intervention) on risk-appropriate colorectal cancer screening (i.e. the right screening test, FOBT or colonoscopy, based on a person’s 10-year absolute risk of colorectal cancer) compared with generic cancer prevention information.
Timepoint [1] 325478 0
12 months post-recruitment.
Secondary outcome [1] 388079 0
Risk perception: personal perceived risk, absolute and comparative, will be measured using an existing validated tool - the 'Family History Questionnaire'.
Timepoint [1] 388079 0
Baseline, 1 month, 6 months and 12 months after recruitment.
Secondary outcome [2] 389091 0
Cancer-specific anxiety (validated questionnaire, cancer worry scale)
Timepoint [2] 389091 0
Baseline, 1 month, 6 months and 12 months after recruitment.
Secondary outcome [3] 390032 0
Cancer screening intentions based on items from the Theory of Planned Behaviour
Timepoint [3] 390032 0
Baseline, 1 month, 6 months and 12 months after recruitment.
Secondary outcome [4] 390033 0
Elements known to influence CRC screening behaviour based on the Preventative Health Model (validated questionnaire, including salience and coherence, response efficacy, cancer worries, social influence, self-efficacy)
Timepoint [4] 390033 0
Baseline, 1 month, 6 months and 12 months after recruitment.
Secondary outcome [5] 390503 0
Proportion of participants who have had risk-appropriate screening after 5 years' follow-up, measured as above for primary endpoint. We will ask for permission to access GP records, records from Medicare (MBS) and from the National Bowel Screening Program (NBCSP) to determine screening undertaken at 5 years.
Timepoint [5] 390503 0
5 years post recruitment

Eligibility
Key inclusion criteria
•Eligible participants for the trial are aged between 45 and 70 years old
•Participants able to read and write English and competent to give informed consent
•Participants who are contactable over the next 12 months for the study follow-up

Inclusion restricted to patients that are potentially due for some form of bowel cancer screening within the next 12 months, i.e.:
o All patients aged 45-50 will be, included as we will not know their genomic risk pre-recruitment. Some will be at increased risk and therefore be recommended early screening in the study;
o Those aged 50-70 years of age who report not having an FOBT in last 2 years.
Minimum age
45 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
•Patients with a previous diagnosis of colorectal cancer are excluded
•Patients with at least one grandparent was born in Africa or is of African ethnicity are ineligible to participate due to the specificity of the DNA test
•Patients with a known genetic predistortion to colorectal cancer or a family history of cancer that requires referral for assessment of a genetic predisposition to colorectal cancer are excluded (according to the NHMRC guidelines). This includes:
o Those confirmed as carrying a pathogenic mutation in a gene associated with a high-risk familial syndrome
o Those with a relative confirmed as carrying a pathogenic mutation in a gene associated with a high-risk familial syndrome, who have not themselves been tested
o Those with or those with a relative with familial adenomatous polyposis
o Those with a relative with multiple colorectal cancers
o Those with at least three first-degree or second-degree relatives with a Lynch syndrome-related cancer (colorectal, endometrial, ovarian, stomach, small bowel, renal pelvis or ureter, biliary tract, brain) with at least one diagnosed before age 55 years).

Patients with recent rectal bleeding or inflammatory bowel disease are excluded and referred for assessment by their GP because they may require colonoscopy as a diagnostic rather than screening procedure.

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)
Baseline data will be entered into an online trial database prior to randomisation; participants will be randomly allocated 1:1 to intervention or control. The allocation sequence will be computer generated to ensure allocation concealment, sequentially within each stratum (general practice) using a biased-coin algorithm (34) that will be embedded within the online database.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Using restricted randomisation within the stratum ensures that the number of individuals is balanced between study groups within each stratum and the stratification factors will be balanced in each study group
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
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)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 307018 0
Government body
Name [1] 307018 0
Cancer Australia
Address [1] 307018 0
Locked Bag 3, Strawberry Hills
NSW 2012
Country [1] 307018 0
Australia
Primary sponsor type
University
Name
The University of Melbourne
Address
Parkville Melbourne VIC 3010
Country
Australia
Secondary sponsor category [1] 307588 0
None
Name [1] 307588 0
Address [1] 307588 0
Country [1] 307588 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307149 0
Medicine and Dentistry Human Ethics Sub-Committee
Ethics committee address [1] 307149 0
Medicine and Dentistry HESC
The University of Melbourne
Parkville Melbourne VIC 3010
Ethics committee country [1] 307149 0
Australia
Date submitted for ethics approval [1] 307149 0
05/08/2020
Approval date [1] 307149 0
05/10/2020
Ethics approval number [1] 307149 0
2057592

Summary
Brief summary
The SCRIPT Trial: A study of DNA testing to tailor bowel cancer screening in primary care.

What is the purpose of this research?
In Australia anyone aged 50-74 should have some sort of bowel cancer screening. People at increased rick of bowel cancer should start screening earlier. Screening is a highly effective way to diagnose bowel cancer earlier and save your life. There are two main ways you can be screened for bowel cancer, by FOBT (or poo test) or colonoscopy. Depending on your risk of getting bowel cancer, the age when you start and the type of bowel cancer screening will vary.

Who is this for?
People with a GP appointment at participating General Practices, aged 45 to 70 years who have not previously been diagnosed with bowel cancer.

Study Details:
Once agreed and consented to take part, the researcher will ask some health questions then provide a DNA test to inform of bowel cancer risk. The researcher will discuss this test with the participant beforehand and the DNA sample is by a self collected mouth swab. After this the participant is placed at random into one of two groups. Randomisation means that you are put into a group by chance, like the toss of a coin. Neither the participant or their doctors can chose which group.
If in the intervention group, after 2 weeks the participant will meet with the researcher at the GP practice or by phone to discuss the DNA test results. They will be given a report summarising their bowel cancer risk and screening recommendations to be discussed with their GP.
For the control group, they will have a consultation with the researcher to discuss cancer risk, lifestyle factors and bowel cancer screening options. They will be given the option to receive their bowel cancer risk results after 12 months from recruitment.
Follow up questionnaires will be sent to all participants at 1, 6 and 12 months after recruitment.
Trial website
nil
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 106202 0
Prof Jon Emery
Address 106202 0
Centre for Cancer Research
Faculty of Medicine, Dentistry and Health Sciences
University of Melbourne
Level 10, Victorian Comprehensive Cancer Centre
305 Grattan St
Melbourne Victoria 3000
Country 106202 0
Australia
Phone 106202 0
+61 03 85597044
Fax 106202 0
Email 106202 0
jon.emery@unimelb.edu.au
Contact person for public queries
Name 106203 0
Ms Sibel Saya
Address 106203 0
Centre for Cancer Research
Faculty of Medicine, Dentistry and Health Sciences
University of Melbourne
Level 10, Victorian Comprehensive Cancer Centre
305 Grattan St
Melbourne Victoria 3000
Country 106203 0
Australia
Phone 106203 0
+61 03 85597189
Fax 106203 0
Email 106203 0
sibel.saya@unimelb.edu.au
Contact person for scientific queries
Name 106204 0
Ms Sibel Saya
Address 106204 0
Centre for Cancer Research
Faculty of Medicine, Dentistry and Health Sciences
University of Melbourne
Level 10, Victorian Comprehensive Cancer Centre
305 Grattan St
Melbourne Victoria 3000
Country 106204 0
Australia
Phone 106204 0
+61 03 85597189
Fax 106204 0
Email 106204 0
sibel.saya@unimelb.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
confidential data will be collected
What supporting documents are/will be available?
Study protocol
Ethical approval
How or where can supporting documents be obtained?
Type [1] 9507 0
Study protocol
Citation [1] 9507 0
Study protocol can be obtained from the study coordinator.
Link [1] 9507 0
Email [1] 9507 0
sibel.saya@unimelb.edu.au
Other [1] 9507 0
No yet available
Attachment [1] 9507 0
Type [2] 9808 0
Ethical approval
Citation [2] 9808 0
Link [2] 9808 0
Email [2] 9808 0
Other [2] 9808 0
Summary results
No Results