Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000905561
Ethics application status
Approved
Date submitted
1/05/2024
Date registered
24/07/2024
Date last updated
24/07/2024
Date data sharing statement initially provided
24/07/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Using genetic information to assist treatment decision making for people on active surveillance following diagnosis with favourable intermediate-risk prostate cancer
Scientific title
GenI-AIRSPACE: Evaluating the effect of genomically informed treatment decision-making on long-term oncological outcomes for individuals diagnosed with intermediate risk prostate cancer undergoing active surveillance(ANZUP 2102)
Secondary ID [1] 311965 0
ANZUP 2102
Universal Trial Number (UTN)
Trial acronym
GenI-AIRSPACE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Intermediate Risk Prostate Cancer 333567 0
Condition category
Condition code
Cancer 330252 330252 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental Arm: Genomically Informed Risk Stratification
Participants assigned to the experimental arm will undergo genomic testing of prospectively collected blood and archival tissue to determine their genomically informed risk stratification.

Upon confirmation of eligibility, consent, and randomisation into the trial, tissue samples from the initial prostate biopsy conducted at the time of diagnosis with intermediate risk prostate cancer will be obtained from relevant pathology providers. Additionally, a 10mL blood sample (approximately 2 teaspoons) will be collected at local pathology providers. . Hematoxylin and eosin (H&E) slides, along with 5µm thick serial sections of biopsy tumour cores on uncharged slides, will be prepared for testing. An optional tumour tissue sample may be collected and analysed at cancer progression.

The following assessments will be performed on samples:
• Germline screening for prostate cancer high risk variants, using a DNA Damage Response Gene+ assay
• Somatic tumour panel using archival tissue using the Illumina TSO500
• Tissue based transcriptional gene signatures using the Decipher Prostate Cancer Test

These assessments are commercially available, however, they are not offered as part of standard care in prostate cancer. It may take between 8-12 weeks for results to become available.

Participants will be assigned as genomic ‘high-risk’ if a listed deleterious germline or somatic mutation is identified, or a Decipher ‘high-risk’ score is returned. Participants without any deleterious germline or somatic mutation, or with a Decipher ‘low- or intermediate-risk’ score will be categorised as genomic ‘low-risk’. This will be communicated both verbally and in writing to the participant as well as their referring clinician using a standard template to assist in treatment decision-making. At the time of providing results, no explicit treatment recommendation will be made – specifically, in patients who are labelled as ‘high-risk’, a recommendation to proceed with radical treatment will not be made. Rather the information will be provided to both the patient and the physician, and the treatment pathway arrived at through shared decision-making.

Risk stratification assessments will remain identical in all stages of the trial, with exception of Stage 1 where germline screening assessment is not mandated. In Stage 1, participants will only be required to provide tissue samples to facilitate somatic tumour panel and Decipher risk score analyses. In the event of a ‘high-risk’ classification on the somatic tumour panel, germline screening will be offered to participants as an optional test which will require the collection of a whole blood sample. Upon the commencement of Stage 2, it will be mandatory for all new participants randomised to the genomically informed arm in Stages 2 and 3 to supply blood samples for germline screening.

The difference between each stage is the follow-up time required to achieve each primary endpoint: 6 months for Stage 1, 3 years for Stage 2, and 10 years for Stage 3. The activities associated with follow-up remain consistent throughout all stages of the trial.

Participants will be asked to complete questionnaires focusing on health related quality of life at baseline and then every 6 months for the first 12 months after randomisation, then every 12 months until the end of follow-up.

Participants will be followed-up for six months in stage 1, three years in stage 2 and ten years in stage 3. Each stage will be conducted in sequence. If the study progresses into the next stage, follow-up period will be extended to reflect the required duration of the next stage. Therefore, the maximum period of follow-up is approximately ten years.
Intervention code [1] 328424 0
Diagnosis / Prognosis
Intervention code [2] 328425 0
Early detection / Screening
Comparator / control treatment
Standard of Care arm
Participants assigned to this arm will continue in usual care with their treating team. This may include active monitoring, as a component of active surveillance, which consists of routine clinical review, PSA evaluation, prostate imaging and/or biopsy per local guidelines/practice.

Follow-up will be conducted throughout the trial period, continuing both before and after definitive treatment (if this occurs).

Participants will be asked to complete questionnaires focusing on health related quality of life at baseline and then every 6 months for the first 12 months after randomisation, then every 12 months until the end of follow-up.
Control group
Active

Outcomes
Primary outcome [1] 337997 0
Stage 1: The number of individuals in the experimental arm continuing in active surveillance 6 months post-diagnosis compared to standard of care arm.
Timepoint [1] 337997 0
Date of randomisation to the date of cessation of active surveillance - assessed up to 6 months following randomisation
Primary outcome [2] 337998 0
Stage 2: The number of individuals in the experimental arm free from active treatment 3 years post-diagnosis compared to the standard of care arm.
Timepoint [2] 337998 0
Date of randomisation to the date of definitive treatment for prostate cancer - assessed up to 3 years following randomisation
Primary outcome [3] 337999 0
Stage 3: 10-year metastasis-free survival.
Timepoint [3] 337999 0
Date of randomisation to the date of first evidence of metastasis - assessed up to study completion, approximately 10 years from recruitment.
Secondary outcome [1] 434073 0
To assess patient-reported urinary function outcomes associated with genomically informed active surveillance.
Timepoint [1] 434073 0
Baseline, 6 monthly for the first 12 months after randomisation, then every 12 months until the end of follow-up.

Participants will be followed-up for six months in stage 1, three years in stage 2 and ten years in stage 3. Each stage will be conducted in sequence. If the study progresses into the next stage, follow-up period will be extended to reflect the required duration of the next stage. Therefore, the maximum period of follow-up is approximately ten years.
Secondary outcome [2] 434074 0
To assess patient-reported sexual function outcomes associated with genomically informed active surveillance
Timepoint [2] 434074 0
Baseline, 6 monthly for the first 12 months after randomisation, then every 12 months until the end of follow-up (6 months for Stage 1, 3 years for Stage 2, and 10 years for Stage 3)

Participants will be followed-up for six months in stage 1, three years in stage 2 and ten years in stage 3. Each stage will be conducted in sequence. If the study progresses into the next stage, follow-up period will be extended to reflect the required duration of the next stage. Therefore, the maximum period of follow-up is approximately ten years.
Secondary outcome [3] 437065 0
To assess patient-reported bowel function outcomes associated with genomically informed active surveillance
Timepoint [3] 437065 0
Baseline, 6 monthly for the first 12 months after randomisation, then every 12 months until the end of follow-up.

Participants will be followed-up for six months in stage 1, three years in stage 2 and ten years in stage 3. Each stage will be conducted in sequence. If the study progresses into the next stage, follow-up period will be extended to reflect the required duration of the next stage. Therefore, the maximum period of follow-up is approximately ten years.
Secondary outcome [4] 437066 0
To assess patient-reported health-related quality of life outcomes associated with genomically informed active surveillance
Timepoint [4] 437066 0
Baseline, 6 monthly for the first 12 months after randomisation, then every 12 months until the end of follow-up.

Participants will be followed-up for six months in stage 1, three years in stage 2 and ten years in stage 3. Each stage will be conducted in sequence. If the study progresses into the next stage, follow-up period will be extended to reflect the required duration of the next stage. Therefore, the maximum period of follow-up is approximately ten years.
Secondary outcome [5] 437067 0
Resource utilisation associated with using genomic tests to inform treatment in a health economics analysis.
Timepoint [5] 437067 0
EORTC QLU-C10D will be performed at baseline, 6 monthly for the first 12 months after randomisation, then every 12 months until the end of follow-up. Resource utilisation data, compiled with questionnaire responses, will contribute the longer-term (10 year) comparative assessment of the costs of using genomic tests to inform decision-making.

Participants will be followed-up for six months in stage 1, three years in stage 2 and ten years in stage 3. Each stage will be conducted in sequence. If the study progresses into the next stage, follow-up period will be extended to reflect the required duration of the next stage. Therefore, the maximum period of follow-up is approximately ten years.

Eligibility
Key inclusion criteria
1. Age 18 years and over.
2. Histological diagnosis of prostate adenocarcinoma with no evidence of metastatic disease on staging investigations (if indicated).
3. Intermediate risk prostate cancer as defined clinical stage cT2 OR Gleason Sum 3+4 = 7 (International Society of Urological Pathology (ISUP) grade group 2) OR Prostate-specific antigen test (PSA) 10-20 ng/mL.
4. Fit for radical treatment (either surgery or radiation) at the time of diagnosis.
5. Estimated life expectancy > 10 years.
6. Availability of formalin-fixed, paraffin-embedded tissue cores for genomic testing.
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Unwilling to accept active surveillance as an initial management strategy.
2. The presence of any variant prostate cancer histology (ductal, small cell, sarcomatoid, urothelial, squamous/adenosquamous carcinoma and basal cell carcinoma).
3. The presence of high-risk pattern 4 growth patterns (in the pattern 4 component of Gleason 3+4 disease), namely intraductal carcinoma or large cribriform pattern.
4. Unable or unwilling to provide informed consent.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised between current standard of care, and genomically informed risk stratification (experimental arm) using a block randomisation method (1:1). Stratification by recruitment site and number of prostate sectors involved (<2 vs. >2) will occur.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety
Statistical methods / analysis
There will be 112 participants recruited to GenI-AIRSPACE Stage 1, 348 to stage 2 and 1950 to stage 3 (inclusive of those enrolled in stages 1 and 2). The overall conduct of the study is sequential: completion of Stage 1 is critical to enable Stages 2 and 3 to be performed.

Assuming a standard care MFS at 10 years of 8% and a genomically informed care MFS at 10 years of 10% a total sample size of 1754 participants (877 per arm) will be required at analysis to have 90% power to determine non-inferiority to within a margin of 2% MFS using a one-sided alpha of 0.05. The target recruitment sample size is planned to be 1950 patients in order to adjust for an anticipated 10% drop out rate

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
31/07/2024
Actual
Date of last participant enrolment
Anticipated
31/05/2031
Actual
Date of last data collection
Anticipated
31/05/2041
Actual
Sample size
Target
1950
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 26499 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 26751 0
Western Hospital - Footscray - Footscray
Recruitment postcode(s) [1] 42541 0
3050 - Parkville
Recruitment postcode(s) [2] 42799 0
3011 - Footscray

Funding & Sponsors
Funding source category [1] 316307 0
Government body
Name [1] 316307 0
Department of Jobs, Skills, Industry and Regions - Victorian Medical Research Acceleration Fund
Country [1] 316307 0
Australia
Funding source category [2] 316311 0
Other
Name [2] 316311 0
The Advanced Genomics Collaboration Innovation Fund
Country [2] 316311 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Address
Country
Australia
Secondary sponsor category [1] 318492 0
None
Name [1] 318492 0
Address [1] 318492 0
Country [1] 318492 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315125 0
The Royal Melbourne Hospital Human Research Ethics Committee
Ethics committee address [1] 315125 0
Ethics committee country [1] 315125 0
Australia
Date submitted for ethics approval [1] 315125 0
30/11/2022
Approval date [1] 315125 0
12/05/2023
Ethics approval number [1] 315125 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 133742 0
A/Prof Niall Corcoran
Address 133742 0
Western Health - Footscray Hospital, 160 Gordon Street, Footscray, Melbourne, VIC, 3011
Country 133742 0
Australia
Phone 133742 0
+61401527907
Fax 133742 0
Email 133742 0
[email protected]
Contact person for public queries
Name 133743 0
A/Prof Samantha Oakes
Address 133743 0
ANZUP Cancer Trials Group, Level 18, International Tower 3, 300 Barangaroo Avenue, Barangaroo, NSW 2000
Country 133743 0
Australia
Phone 133743 0
+61 02 9054 3600
Fax 133743 0
Email 133743 0
[email protected]
Contact person for scientific queries
Name 133744 0
A/Prof Niall Corcoran
Address 133744 0
Western Health - Footscray Hospital, 160 Gordon Street, Footscray, Melbourne, VIC, 3011
Country 133744 0
Australia
Phone 133744 0
+61401527907
Fax 133744 0
Email 133744 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


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.