Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000053628p
Ethics application status
Submitted, not yet approved
Date submitted
19/12/2022
Date registered
17/01/2023
Date last updated
17/01/2023
Date data sharing statement initially provided
17/01/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
The MAGPIE Study: Multi-cancer genomic risk assessment to target screening in general practice
Scientific title
The MAGPIE Study: Multi-cancer genomic risk assessment to target screening in general practice patients aged 45-59.
Secondary ID [1] 308599 0
None
Universal Trial Number (UTN)
Trial acronym
The MAGPIE Study (Multi-cAncer Genomic risk assessment to target screening in general PractIcE)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 328470 0
Bowel Cancer 328471 0
Prostate Cancer 328472 0
Melanoma 328473 0
Breast cancer screening 328483 0
Bowel cancer screening 328484 0
Prostate cancer screening 328485 0
Skin cancer screening 328486 0
Condition category
Condition code
Cancer 325507 325507 0 0
Breast
Cancer 325508 325508 0 0
Malignant melanoma
Cancer 325509 325509 0 0
Prostate
Cancer 325510 325510 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is testing the behavioural impact of a ‘complex intervention’ which comprises several parts. The main part is a genomic test - (i.e., a personalised risk estimate determined from the participant’s polygenic risk score - which will be collected via a single saliva collection kit; participants self-reported family history of cancer, age and sex) with personalised screening recommendations derived from this risk. The initial consult whereby the genomic risk will be determined will be followed up 2-3 weeks later, whereby participants will be invited to attend a 20-minute one-on-one visit with a researcher to go through their personal risk report, participants will receive their personal risk score report and be given recommendations for screening for each cancer type.

These reports have been developed specifically to inform about risk but also to impact cancer screening behaviour. The risk reports will include clear and succinct written detail about cancer screening recommendations for the four cancers as well as infographics depicting the participants specific risk scores and diagrams that depict the differences in mortality for populations that do and don't screen for the four cancers. All these diagrams and infographics will be discussed during the results meeting with the researcher.
Reports will be given to both participants and GPs by the researcher conducting the results appointments, these will be given to participants and GPs either by hardcopy or provided electronically via email or secure password protected hyperlink

The follow-up consultation between participant and researcher will be conducted in person or via telehealth method - whichever is preferrable to the participant, where a discussion around personal risk and screening pathways for each of the three gender-specific cancers with a risk report for the participant and their GP will be conducted. Participants will then be encouraged to book in to see their GP in order to action any screening recommendations as a result of the risk score report. Over the study period, participants will be required to meet with the researcher twice within an approximate one-month period and will be required to see their GP once during the study period and encouraged to see their GP at least once in order to follow-up and action any screening recommendations. The overall period of the study for participants will be 6-7 months from recruitment.

Calculation of cancer risk from the polygenic risk score: A polygenic risk score will be generated by determining how many risk alleles are present at each of the single nucleotide polymorphisms (SNPs) associated with risk of each cancer. This list of SNPs and relative risks of cancer for each SNP will be determined using the most up-to-date literature: breast cancer (BrCa) 313 SNPs, colorectal cancer (CRC) 140 SNPs, prostate cancer (PrCa) 269 SNPs, melanoma 85 SNPs. Increased risks from a family history of any of the cancers will also be accounted for. This will be calculated using the number and age of diagnosis of any first- or second-degree relatives with the cancer in question. Familial aggregation studies provide published estimates of the relative risk conferred by the presence of the most common combinations of family history for each cancer.

Determination of cancer screening recommendations, incorporating the polygenic risk score-derived ten-year-risks and/or relative risks: Screening for these four cancers is recommended in Australia by determining an individual's risk category (mainly using the presence and strength of a family history of cancer), which in turn has attached screening recommendations. These risk categories have defined risk thresholds. Our intervention uses the same principles and risk thresholds as in the approved guidelines but uses the genomic test (including family history) to determining risk level.

Recommended screening for those at lower-than-average risk: For all cancers, screening recommendations will not be downgraded from what would otherwise be recommended according to the respective Australian guidelines.
- For those without increased risk of CRC: 2-yearly iFOBT will be recommended from 50 years.
- For those without increased risk of BrCa: 2-yearly mammogram will be recommended from 50 years.
- For those without increased risk of PrCa: A consideration of 2-yearly PSA from 50 years will be recommended.
- For those without increased risk of melanoma: SunSmart measures and self-monitoring of any skin changes will be recommended but no screening will be advised.

The guidelines followed for the recommended screening pathways are based off the Revised Australian national guidelines for colorectal cancer screening: family history (2018), Cancer Council Australia Colorectal Cancer Guidelines Working Party. Clinical practice guidelines for the prevention, early detection and management of colorectal cancer (2017), Prostate Cancer Foundation of Australia and Cancer Council Australia PSA Testing Guidelines Expert Advisory Panel. Clinical practice guidelines PSA Testing and Early Management of Test-Detected Prostate Cancer (2016) and The Royal Australian College of General Practitioners. Guidelines for preventive activities in general practice (2016)

Recommended screening for those whose family history meets genetics referral guidelines: Those who meet the referral guidelines due to their family history of cancer will be recommended as part of their personalised screening report to discuss referral to a genetics service with their GP.

Colorectal cancer:
Those who are due an Immunochemical Fecal Occult Blood Test (iFOBT) will be given one by the researcher to discuss with their GP, by their GP directly or by their GP via the National Bowel Cancer Screening Program (NBCSP). All participants who are in the iFOBT screening group will be given a brief demonstration on its use to increase their self-efficacy to perform the test. For those who have reported having polyps found on their last colonoscopy, an information sheet regarding the guidelines on surveillance colonoscopy after polypectomy will be given to participants’ GPs to assist their clinical discussion. For those at increased risk of Colorectal Cancer (CRC), they are recommended to discuss with their GP referral for screening colonoscopy.

Breast cancer:
Those who are due a mammogram will be given the phone number to book a mammogram through BreastScreen Victoria and the website address to book one online. Providing the website and phone number to book a mammogram aims to remove practical barriers to complete the screening.
Mammograms are available through the national screening program for all over 40, with the caveat that those in their 40s should discuss their individual risk factors with their doctor.

Prostate Cancer:
Prostate Specific Antigen (PSA) screening is not universally recommended as a screening test in Australia. Instead, Australian guidelines recommend that for those who request it, GPs should discuss the request with patients and use a decision aid developed to facilitate informed decision making about this test.

Melanoma:
GPs can conduct clinical skin examinations to screen for melanoma. As this is likely to require a dedicated GP appointment, the researcher will offer to assist participants in making an additional appointment at their practice for this purpose.

All final decisions on screening path are made by the participant and their GP together.

In order to monitor adherence to the intervention and effectiveness of the method of intervention, a risk report session attendance checklist will be available within the researcher's secure study redcap database and an audit of GP medical records will be conducted to determine follow-up visits and screening attendance etc.
Intervention code [1] 325044 0
Early detection / Screening
Intervention code [2] 325045 0
Prevention
Intervention code [3] 325049 0
Behaviour
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 333353 0
To measure the effect on screening behaviour of a personalised cancer risk estimate for breast cancer (derived from a polygenic risk score) for primary care patients aged 45-59. The primary outcome is the proportion, for breast cancer, who complete risk-appropriate screening of those who require screening within six months follow up post the genomic risk results.
Screening behaviour will be determined from participant self-report (from the study-specific follow-up questionnaires) and GP record audit. Risk-appropriate screening is defined as being concordant with the screening recommended as part of the intervention. How the risk-appropriate screening recommendations will be derived from the Australian National Screening Guidelines.
Screening behaviour will be obtained from the following sources:
1. Participant self-report;
2. Data from their GP records (results of screening tests for breast cancer e.g. mammogram, breast ultrasound etc.); Processes to obtain consent to access these data will already be established.
Timepoint [1] 333353 0
Baseline (participant recruitment/DNA test) and 6 months (post-recruitment).
1 month, 2 month and 6 month post recruitment questionnaires.
Primary outcome [2] 333429 0
To measure the effect on screening behaviour of a personalised cancer risk estimate for bowel cancer (derived from a polygenic risk score) for primary care patients aged 45-59. The primary outcome is the proportion, for bowel cancer, who complete risk-appropriate screening of those who require screening within six months follow up post the genomic risk results.
Screening behaviour will be determined from participant self-report (from the study-specific follow-up questionnaires) and GP record audit. Risk-appropriate screening is defined as being concordant with the screening recommended as part of the intervention. How the risk-appropriate screening recommendations will be derived from the Australian National Screening Guidelines.
Screening behaviour will be obtained from the following sources:
1. Participant self-report;
2. Data from their GP records (results of screening tests for bowel cancer e.g. iFOBT, colonoscopy etc.); Processes to obtain consent to access these data will already be established.
Timepoint [2] 333429 0
Baseline (participant recruitment/DNA test) and 6 months (post-recruitment).
1 month, 2 month and 6 month post recruitment questionnaires.
Primary outcome [3] 333430 0
To measure the effect on screening behaviour of a personalised cancer risk estimate for prostate cancer (derived from a polygenic risk score) for primary care patients aged 45-59. The primary outcome is the proportion, for prostate cancer, who complete risk-appropriate screening of those who require screening within six months follow up post the genomic risk results.
Screening behaviour will be determined from participant self-report (from the study-specific follow-up questionnaires) and GP record audit. Risk-appropriate screening is defined as being concordant with the screening recommended as part of the intervention. How the risk-appropriate screening recommendations will be derived from the Australian National Screening Guidelines.
Screening behaviour will be obtained from the following sources:
1. Participant self-report;
2. Data from their GP records (results of screening tests for prostate cancer e.g. PSA test, prostate biopsy, discussion about consideration of PSA testing etc.); Processes to obtain consent to access these data will already be established.
Timepoint [3] 333430 0
Baseline (participant recruitment/DNA test) and 6 months (post-recruitment).
1 month, 2 month and 6 month post recruitment questionnaires.
Secondary outcome [1] 416720 0
*PLEASE NOTE THIS IS A FOURTH PRIMARY OUTCOME OF THE STUDY*
To measure the effect on screening behaviour of a personalised cancer risk estimate for melanoma (derived from a polygenic risk score) for primary care patients aged 45-59. The primary outcome is the proportion, for melanoma, who complete risk-appropriate screening of those who require screening within six months follow up post the genomic risk results.
Screening behaviour will be determined from participant self-report (from the follow-up questionnaires) and GP record audit. Risk-appropriate screening is defined as being concordant with the screening recommended as part of the intervention. How the risk-appropriate screening recommendations will be derived from the Australian National Screening Guidelines.
Screening behaviour will be obtained from the following sources:
1. Participant self-report;
2. Data from their GP records (results of screening tests for melanoma e.g. a full body skin check etc.); Processes to obtain consent to access these data will already be established.
Timepoint [1] 416720 0
Baseline (participant recruitment/DNA test) and 6 months (post-recruitment).
1 month, 2 month and 6 month post recruitment questionnaires.
Secondary outcome [2] 417076 0
The secondary objectives of this study are to evaluate the feasibility of implementation of this test in primary care, and the impact on elements known to influence screening behaviour within six months after genomic risk results, compared over time to baseline measures, including:
1. salience and coherence, based on the Preventative Health Model (validated questionnaire)

Semi-structured, one-on-one face-to-face/teletrial interviews with a member of the research team will be conducted to obtain these survey answers.
Timepoint [2] 417076 0
Baseline (at recruitment/DNA test) 1, 2, and 6 months (post recruitment/DNA test).
Secondary outcome [3] 417396 0
The secondary objectives of this study are to evaluate the feasibility of implementation of this test in primary care, and the impact on elements known to influence screening behaviour within six months after genomic risk results, compared over time to baseline measures, including:
2. response efficacy, based on the Preventative Health Model (validated questionnaire)

Semi-structured, one-on-one face-to-face/teletrial interviews with a member of the research team will be conducted to obtain these survey answers.
Timepoint [3] 417396 0
Baseline (at recruitment/DNA test) 1, 2, and 6 months (post recruitment/DNA test).
Secondary outcome [4] 417397 0
The secondary objectives of this study are to evaluate the feasibility of implementation of this test in primary care, and the impact on elements known to influence screening behaviour within six months after genomic risk results, compared over time to baseline measures, including:
3. cancer worries, based on the Preventative Health Model (validated questionnaire)

Semi-structured, one-on-one face-to-face/teletrial interviews with a member of the research team will be conducted to obtain these survey answers.
Timepoint [4] 417397 0
Baseline (at recruitment/DNA test) 1, 2, and 6 months (post recruitment/DNA test).
Secondary outcome [5] 417398 0
The secondary objectives of this study are to evaluate the feasibility of implementation of this test in primary care, and the impact on elements known to influence screening behaviour within six months after genomic risk results, compared over time to baseline measures, including:
4. social influence on/about cancer screening, based on the Preventative Health Model (validated questionnaire)

Semi-structured, one-on-one face-to-face/teletrial interviews with a member of the research team will be conducted to obtain these survey answers.
Timepoint [5] 417398 0
Baseline (at recruitment/DNA test) 1, 2, and 6 months (post recruitment/DNA test).
Secondary outcome [6] 417401 0
The secondary objectives of this study are to evaluate the feasibility of implementation of this test in primary care, and the impact on elements known to influence screening behaviour within six months after genomic risk results, compared over time to baseline measures, including:
5a. self-efficacy to complete cancer screening, using the Preventative Health Model for colorectal cancer screening by Vernon et al. (1997) (validated questionnaire)

Semi-structured, one-on-one face-to-face/teletrial interviews with a member of the research team will be conducted to obtain these survey answers.
Timepoint [6] 417401 0
Baseline (at recruitment/DNA test) 1, 2, and 6 months (post recruitment/DNA test).
Secondary outcome [7] 417584 0
The secondary objectives of this study are to evaluate the feasibility of implementation of this test in primary care, and the impact on elements known to influence screening behaviour within six months after genomic risk results, compared over time to baseline measures, including:

5b. self-efficacy to complete cancer screening, using Informed Prostate Cancer Screening Decision Self-Efficacy Scale for prostate cancer screening by Owens et al. (2020) (validated questionnaire).

Semi-structured, one-on-one face-to-face/teletrial interviews with a member of the research team will be conducted to obtain these survey answers.
Timepoint [7] 417584 0
Baseline (at recruitment/DNA test) 1, 2, and 6 months (post recruitment/DNA test).
Secondary outcome [8] 417585 0
The secondary objectives of this study are to evaluate the feasibility of implementation of this test in primary care, and the impact on elements known to influence screening behaviour within six months after genomic risk results, compared over time to baseline measures, including:

5c. self-efficacy to complete cancer screening, the self-efficacy scale for mammography published by Champion et al., (2008). (validated questionnaire)
Timepoint [8] 417585 0
Baseline (at recruitment/DNA test) 1, 2, and 6 months (post recruitment/DNA test).
Secondary outcome [9] 417586 0
The secondary objectives of this study are to evaluate the feasibility of implementation of this test in primary care, and the impact on elements known to influence screening behaviour within six months after genomic risk results, compared over time to baseline measures, including:

5d. self-efficacy to complete cancer screening, using a sub-section of a skin examination behaviour questionnaire for melanoma published by Kasparian et al. (2012) (validated questionnaire)

Semi-structured, one-on-one face-to-face/teletrial interviews with a member of the research team will be conducted to obtain these survey answers.
Timepoint [9] 417586 0
Baseline (at recruitment/DNA test) 1, 2, and 6 months (post recruitment/DNA test).
Secondary outcome [10] 417587 0
The secondary objectives of this study are to evaluate the feasibility of implementation of this test in primary care, and the impact on elements known to influence screening behaviour within six months after genomic risk results, compared over time to baseline measures, including:
6. cancer-specific anxiety, using the cancer worry scale by Lerman et al. (1991) (validated questionnaire)
Semi-structured, one-on-one face-to-face/teletrial interviews with a member of the research team will be conducted to obtain these survey answers.
Timepoint [10] 417587 0
Baseline (at recruitment/DNA test) 1, 2, and 6 months (post recruitment/DNA test).
Secondary outcome [11] 417588 0
The secondary objectives of this study are to evaluate the feasibility of implementation of this test in primary care, and the impact on elements known to influence screening behaviour within six months after genomic risk results, compared over time to baseline measures, including:
7. psychosocial impact of the personalised risk assessment, using the Multidimensional Impact of Cancer Risk Assessment, MICRA (2002) (validated questionnaire)
Semi-structured, one-on-one face-to-face/teletrial interviews with a member of the research team will be conducted to obtain these survey answers.
Timepoint [11] 417588 0
Baseline (at recruitment/DNA test) 1, 2, and 6 months (post recruitment/DNA test).
Secondary outcome [12] 417589 0
The secondary objectives of this study are to evaluate the feasibility of implementation of this test in primary care, and the impact on elements known to influence screening behaviour within six months after genomic risk results, compared over time to baseline measures, including:
8. cancer risk perception, asking about personal perceived absolute and comparative risk, using validated measures by Gurmankin et al. (2006).
Semi-structured, one-on-one face-to-face/teletrial interviews with a member of the research team will be conducted to obtain these survey answers.
Timepoint [12] 417589 0
Baseline (at recruitment/DNA test) 1, 2, and 6 months (post recruitment/DNA test).
Secondary outcome [13] 417590 0
The secondary objectives of this study are to evaluate the feasibility of implementation of this test in primary care, and the impact on elements known to influence screening behaviour within six months after genomic risk results, compared over time to baseline measures, including:
9. cancer screening intentions, developed for this study. Questions are based on the Theory of Planned Behaviour by Connor & Sparks (1996)

Semi-structured, one-on-one face-to-face/teletrial interviews with a member of the research team will be conducted to obtain these survey answers.
Timepoint [13] 417590 0
Baseline (at recruitment/DNA test) 1, 2, and 6 months (post recruitment/DNA test).

Eligibility
Key inclusion criteria
Potential participants are those seeing a consented GP at the recruited clinics who meet all of the following criteria:
• Are aged between 45 and 59 years
• Are able to read and write English and competent to give informed consent
• Are contactable over the next six months for the study follow-up
Minimum age
45 Years
Maximum age
59 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Have been diagnosed with any of breast, prostate, colorectal cancer or melanoma;
- Have any alarm symptoms that are indicative of the cancers included in the risk assessment:
Once or more and uninvestigated:
- Blood in stool or urine
oFor more than four weeks and uninvestigated:
- Problems with urination
- Diarrhoea
- Unexplained weight loss
- An unusual pain, lump or swelling anywhere in your body
- A new or changed spot on your skin;

- Have a known genetic predisposition to any of the four cancers in question or, a first-/second-degree relative with a genetic predisposition and the participants has not had genetic testing themselves. This is defined by a mutation in any of the following genes:
- CRC: Lynch syndrome (MLH1, PMS2, MSH2, MSH6, EPCAM), familial adenomatous polyposis (APC);
- BrCa: BRCA1, BRCA2, PALB2, ATM, CHEK2;
- PrCa: BRCA1, BRCA2, HOXB13;
- Melanoma: CDKN2A/p16.

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
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
1/02/2023
Actual
Date of last participant enrolment
Anticipated
31/07/2023
Actual
Date of last data collection
Anticipated
31/01/2024
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 312845 0
Charities/Societies/Foundations
Name [1] 312845 0
Cancer Council Victoria
Country [1] 312845 0
Australia
Funding source category [2] 312847 0
University
Name [2] 312847 0
University of Melbourne
Country [2] 312847 0
Australia
Primary sponsor type
University
Name
University of Melbourne
Address
Grattan Street, Parkville, Victoria, 3010
Country
Australia
Secondary sponsor category [1] 314495 0
None
Name [1] 314495 0
Address [1] 314495 0
Country [1] 314495 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 312122 0
Medicine and Dentistry Human Ethics Sub-Committee (STEMM 2)
Ethics committee address [1] 312122 0
Level 5, Alan Gilbert Building, 161 Barry Street, Carlton
The University of Melbourne, Victoria 3010 Australia
Ethics committee country [1] 312122 0
Australia
Date submitted for ethics approval [1] 312122 0
18/11/2022
Approval date [1] 312122 0
Ethics approval number [1] 312122 0

Summary
Brief summary
The MAGPIE Study:

What is the purpose of this research?
This research aims to transform early detection of Australia’s four most common cancers (colorectal, breast, prostate, melanoma) by identifying those at risk more accurately and encouraging all Australians to do the right cancer screening tests for their personal risk. We can do this by offering in general practices a new genomic test that predicts future risk of cancer. This risk information will be used to tailor screening recommendations, then to have a discussion to encourage the right decisions about screening for each patient.

Who is this for?
People with a GP appointment at participating General Practices, aged 45 to 59 years who have not previously been diagnosed with bowel, breast, prostate cancer or malignant melanoma.

Study Details:
Once agreed and consented to take part, the researcher will ask some health questions then provide a DNA test to inform of multi-cancer risk. The researcher will discuss this test with the participant beforehand and the DNA sample is by a self-collected saliva swab. After 2-3 weeks the participant will meet with the researcher at the GP practice or by method of telehealth appointment to discuss the DNA test results. They will be given a report summarising their multi-cancer risk and screening recommendations to be discussed with their GP. Follow up questionnaires will be sent to all participants at 1, 2 and 6 months after recruitment.

It is hoped that this study will determine whether providing participants with their personalised cancer risk factors has a positive impact upon their willingness to undergo cancer screening procedures. If this study does show a positive effect, it will facilitate provision of DNA testing for cancer risk in general practice and therefore personalised population cancer screening for all Australians.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 123558 0
Dr Sibel Saya
Address 123558 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 123558 0
Australia
Phone 123558 0
+61 03 85597189
Fax 123558 0
Email 123558 0
[email protected]
Contact person for public queries
Name 123559 0
Dr Sibel Saya
Address 123559 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 123559 0
Australia
Phone 123559 0
+61 03 85597189
Fax 123559 0
Email 123559 0
[email protected]
Contact person for scientific queries
Name 123560 0
Dr Sibel Saya
Address 123560 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 123560 0
Australia
Phone 123560 0
+61 03 85597189
Fax 123560 0
Email 123560 0
[email protected]

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?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
17846Study protocol  [email protected] Study protocol can be obtained from the study coor... [More Details]
17847Ethical approval    Not yet available



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.