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Trial registered on ANZCTR


Registration number
ACTRN12621001756819
Ethics application status
Approved
Date submitted
11/10/2021
Date registered
22/12/2021
Date last updated
2/08/2023
Date data sharing statement initially provided
22/12/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Three versus five years of adjuvant Imatinib as treatment for patients with operable gastrointestinal stromal tumour (GIST) with a high risk for recurrence: SSGXXII: A Randomised phase III study
Scientific title
Three versus five years of adjuvant Imatinib as treatment for patients with operable gastrointestinal stromal tumour (GIST) with a high risk for recurrence: SSGXXII: A Randomised phase III study
Secondary ID [1] 305330 0
Protocol number: CTC 0275
Secondary ID [2] 305331 0
AGITG Protocol Number: AG0221GS
Universal Trial Number (UTN)
Trial acronym
SSGXXII
Linked study record
Trial EudraCT number: 2014-000898-39
(This record is for the Australian sites which will be recruiting under the same trial protocol. The trial is recruiting under the EudraCT registration in Finland, Sweden, Austria, Spain, Germany, Norway, Netherlands, Denmark, UK).

Health condition
Health condition(s) or problem(s) studied:
Gastrointestinal stromal tumour (GIST) 323645 0
Condition category
Condition code
Cancer 321185 321185 0 0
Stomach
Cancer 321416 321416 0 0
Oesophageal (gullet)
Cancer 321417 321417 0 0
Bowel - Anal
Cancer 321418 321418 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 321419 321419 0 0
Bowel - Small bowel (duodenum and ileum)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following completion of 35-38 months of standard of care Imatinib treatment (defined as 200-800mg daily oral tablet), patients will be enrolled and randomised to receive continued Imatinib oral tablets at 400 mg/day for 24 months, or to receive no further imatinib treatment.

Pharmacy teams will monitor returned imatinib packaging to ensure adherence to the oral medication.
Intervention code [1] 321880 0
Treatment: Drugs
Comparator / control treatment
No further Imatinib or other anti-cancer treatment. Patients randomised to the comparator arm receive no trial intervention.
Control group
Active

Outcomes
Primary outcome [1] 329149 0
Recurrence-free survival
Defined as the time from the date of randomisation to GIST recurrence or death.
Assessed by CT/MRI scans and patient follow-up.
Timepoint [1] 329149 0
Scans every 6 months for 5 years, then every 12 months to 10 years.
Secondary outcome [1] 401657 0
Overall survival
Time from the date of randomisation to death.
Timepoint [1] 401657 0
Follow-up of patients every 3 months for 4 years, then every 6 months to 5 years, then every 12 months to 10 years.
Secondary outcome [2] 401658 0
GIST-specific survival
Time from the date of randomisation to the date of death considered to be caused by GIST.
Timepoint [2] 401658 0
CT/MRI scans every 6 months for 5 years, then every 12 months to 10 years.
Secondary outcome [3] 401659 0
Adverse effects.
Adverse effects considered to be related to the treatment, as recorded by investigators following clinical assessment of patients. Possible/known adverse effects include low red blood cells, white blood cells and platelets which can together lead to bleeding, easy bruising, fatigue, shortness of breath and weakness. A full list of possible adverse effects is listed in the patient information sheet.
Timepoint [3] 401659 0
Every 3 months for 27 months.
Secondary outcome [4] 401660 0
Quality of life, assessed by EQ-5D-5L.
Timepoint [4] 401660 0
Every 3 months for 27 months.
Secondary outcome [5] 401743 0
Exploratory endpoints relating to GIST recurrence free survival (effects of tumour mutation type, tumour site, imatinib dose at randomisation, use of tissue/blood molecular markers as predictors).
Timepoint [5] 401743 0
Assessed at end of study (10 years).

Eligibility
Key inclusion criteria
1, Age >= 18 years.
2. Morphological and immunohistological documentation of GIST (immunostaining for KIT[CD117] and/or DOG-1 positive, or mutation of KIT or PDGFRA present in tumor tissue).
3. Macroscopically complete surgical resection of GIST (either R0 or R1 resection).
4. Mutation analysis of KIT and PDGFR genes has been carried out.
5. A high risk of GIST recurrence; either gastric GIST with mitotic count >10/50 HPFs or >10/5mm2; OR non-gastric GIST with mitotic count >5/50 HPFs or >5/5mm2; OR non-gastric GIST treated with neoadjuvant imatinib and initially larger than 10cm; OR tumor rupture.
6. Eastern Cooperative Oncology Group performance status <= 2.
7. Adequate organ function.
8. Female patients of childbearing potential must have a negative pregnancy test within 14 days before initiation of study drug dosing. Postmenopausal women must have amenorrhea for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
9. Patient willing to be followed up at the study site regardless of the result of randomization.
10. Patient has provided a written, voluntary informed consent prior to study-specific screening procedures.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Presence of distant metastases or local recurrence of GIST.
2. Not willing to donate tumor tissue and/or blood samples for the study molecular studies.
3. Presence of a substitution mutation at PDGFRA codon D842 (usually D842V).
4. Administration of adjuvant imatinib longer than for 3 years is planned regardless of the result of randomization, or "life long" imatinib administration is planned.
5. Prior adjuvant (+ neoadjuvant) therapy with imatinib mesylate for at least 35 months has not been completed, or the total duration of prior adjuvant (+ neoadjuvant) imatinib administration exceeds the total duration of 38 months.
6. Neoadjuvant imatinib for a duration that exceeds 12 months.
7. Longer than 4-week break during adjuvant imatinib administration.
8. The dose of imatinib at completion of 3 years of adjuvant imatinib was 200 mg per day or less or greater than 800 mg per day.
9. Patient has received any investigational anti-cancer agents during adjuvant imatinib or between completion of adjuvant imatinib and the date of randomization.
10. Patient has been free of another malignancy for less than 5 years except if the other malignancy is not currently clinically significant nor requiring active intervention, or if the other malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Recent existence of any other malignant disease is not allowed.
11. Patient with Grade III/IV cardiac disease as defined by the New York Heart Association Criteria (i.e., congestive heart failure, myocardial infarction within 6 months of study entry).
12.Female patients who are pregnant or breast-feeding.
13. Severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, severe chronic renal disease, or active uncontrolled infection).
14. Known diagnosis of human immunodeficiency virus (HIV) infection.
15. Patient with a significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
16. Inability or difficulty in swallowing tablets.
17. Patients with chronic or active hepatitis B.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
17/01/2022
Actual
17/02/2022
Date of last participant enrolment
Anticipated
Actual
31/05/2023
Date of last data collection
Anticipated
31/12/2034
Actual
Sample size
Target
25
Accrual to date
Final
13
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 25312 0
The Alfred - Melbourne
Recruitment hospital [2] 25313 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [3] 25314 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [4] 25315 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [5] 25316 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [6] 25317 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [7] 25318 0
Peninsula Oncology Centre - Frankston
Recruitment hospital [8] 25319 0
Lake Macquarie Private Hospital - Gateshead
Recruitment postcode(s) [1] 40988 0
3004 - Melbourne
Recruitment postcode(s) [2] 40989 0
3000 - Melbourne
Recruitment postcode(s) [3] 40990 0
2065 - St Leonards
Recruitment postcode(s) [4] 40991 0
4029 - Herston
Recruitment postcode(s) [5] 40992 0
6150 - Murdoch
Recruitment postcode(s) [6] 40993 0
5011 - Woodville
Recruitment postcode(s) [7] 40994 0
3199 - Frankston
Recruitment postcode(s) [8] 40995 0
2290 - Gateshead

Funding & Sponsors
Funding source category [1] 309688 0
Government body
Name [1] 309688 0
Medical Research Future Fund - International Clinical Trials Collaboration Grant
Country [1] 309688 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Gastro-Intestinal Trials Group (AGITG)
Address
119-143 Missenden Road
Camperdown, NSW 2050
Country
Australia
Secondary sponsor category [1] 311114 0
Other Collaborative groups
Name [1] 311114 0
Scandinavian Sarcoma Group (SSG)
Address [1] 311114 0
Barngatan 4
SE-221 85 Lund
Country [1] 311114 0
Sweden
Other collaborator category [1] 282018 0
University
Name [1] 282018 0
University of Sydney
Address [1] 282018 0
NHMRC CTC
119-143 Missenden Rd
Camperdown, NSW 2050
Country [1] 282018 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309457 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 309457 0
Ethics committee country [1] 309457 0
Australia
Date submitted for ethics approval [1] 309457 0
Approval date [1] 309457 0
13/07/2021
Ethics approval number [1] 309457 0

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

Contacts
Principal investigator
Name 114222 0
Prof John Zalcberg
Address 114222 0
The Alfred Hospital
55 Commercial Rd, Melbourne VIC 3004
Country 114222 0
Australia
Phone 114222 0
+61 2 9562 5006
Fax 114222 0
Email 114222 0
ssgxxii.study@sydney.edu.au
Contact person for public queries
Name 114223 0
Ailsa Langford
Address 114223 0
NHMRC CTC, University of Sydney
119-143 Missenden Road,
Camperdown, NSW 2050
Country 114223 0
Australia
Phone 114223 0
+61 2 9562 5000
Fax 114223 0
Email 114223 0
ssgxxii.study@sydney.edu.au
Contact person for scientific queries
Name 114224 0
Ailsa Langford
Address 114224 0
NHMRC CTC, University of Sydney
119-143 Missenden Road,
Camperdown, NSW 2050
Country 114224 0
Australia
Phone 114224 0
+61 2 9562 5000
Fax 114224 0
Email 114224 0
ssgxxii.study@sydney.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


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.