Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12605000138684
Ethics application status
Approved
Date submitted
9/08/2005
Date registered
12/08/2005
Date last updated
18/12/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Advanced GIST
Scientific title
Phase III, randomised, intergroup, international trial assessing the clinical activity of STI571 at two dose levels in patients with unresectable or metastatic gastrointestional stromal tumors (GIST) expressing the kit receptor tyrosine kinase (CD117)
Secondary ID [1] 114 0
European Organisation for Research and Treatment of Cancer (EORTC): EORTC 62005
Secondary ID [2] 115 0
National Clinical Trials Registry: NCTR465
Universal Trial Number (UTN)
Trial acronym
Advanced GIST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Patients with unresectable or metastatic gastrointestional stromal tumors (GIST) expressing the kit receptor tyrosine kinase (CD117) 228 0
Condition category
Condition code
Cancer 259 259 0 0
Stomach

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
It is the study of two doses (400mg and 800mg) of STI571 (Imatinib mesylate) to test whether any relevant dose/activity relationship is detectable in patients with unresectable or metastatic gastrointestional stromal tumors (GIST) expressing the kit receptor tyrosine kinase (CD117). Patients will receive study drug until disease progression or unacceptable toxicity.
Intervention code [1] 138 0
Treatment: Drugs
Comparator / control treatment
No comparator
Control group
Dose comparison

Outcomes
Primary outcome [1] 304 0
To compare the outcome of patients with with unresectable or metastatic gastrointestional stromal tumors (GIST) expressing the kit receptor tyrosine kinase (CD117) treated with low versus high doses of STI571.
Timepoint [1] 304 0
After 170 events (progression or death)
Secondary outcome [1] 675 0
To assess response rates of patients with these two doses of STI571.
Timepoint [1] 675 0
After 170 events (progression or death)
Secondary outcome [2] 676 0
To assess toxicities of patients with these two doses of STI571.
Timepoint [2] 676 0
After 170 events (progression or death)

Eligibility
Key inclusion criteria
1. Documented diagnosis of GIST with kit expression. 2. At lease one measureable or evaluable site of disease. 3. Performance status 0,1,2 or 3 (ECOG).
Minimum age
Not stated
Maximum age
Not stated
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1.Patient has received chemotherapy or any other investigational agent within in last 28 days 2. Patient with Grade III/IV cardiac problems 3. Known brain metastasis

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)
Allocation was made from a central website - EORTC.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random allocation sequence stratification by institution, measurability of disease (measurable versus non-measurable) and performance status (WHO 0-2 Vs 3)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
7/02/2001
Actual
13/06/2001
Date of last participant enrolment
Anticipated
Actual
7/02/2002
Date of last data collection
Anticipated
Actual
10/10/2016
Sample size
Target
946
Accrual to date
Final
946
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 9583 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 9584 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [3] 9585 0
Westmead Hospital - Westmead
Recruitment hospital [4] 9586 0
Prince of Wales Hospital - Randwick
Recruitment hospital [5] 9587 0
St George Hospital - Kogarah
Recruitment hospital [6] 9588 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment hospital [7] 9589 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [8] 9590 0
Ashford Cancer Centre: Adelaide Cancer Centre - Kurralta Park
Recruitment hospital [9] 9591 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [10] 9592 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [11] 9593 0
Western Hospital - Footscray
Recruitment hospital [12] 9594 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [13] 9595 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [14] 9596 0
The Wesley Hospital - Auchenflower
Recruitment hospital [15] 9597 0
Launceston General Hospital - Launceston
Recruitment hospital [16] 9598 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [17] 9599 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 18342 0
2031 - Randwick
Recruitment postcode(s) [2] 18339 0
2050 - Camperdown
Recruitment postcode(s) [3] 18340 0
2065 - St Leonards
Recruitment postcode(s) [4] 18341 0
2145 - Westmead
Recruitment postcode(s) [5] 18344 0
2200 - Bankstown
Recruitment postcode(s) [6] 18343 0
2217 - Kogarah
Recruitment postcode(s) [7] 18347 0
3000 - Melbourne
Recruitment postcode(s) [8] 18348 0
3220 - Geelong
Recruitment postcode(s) [9] 18350 0
4029 - Herston
Recruitment postcode(s) [10] 18352 0
4066 - Auchenflower
Recruitment postcode(s) [11] 18351 0
4102 - Woolloongabba
Recruitment postcode(s) [12] 18349 0
5022 - Henley Beach
Recruitment postcode(s) [13] 18346 0
5037 - Kurralta Park
Recruitment postcode(s) [14] 18345 0
5042 - Bedford Park
Recruitment postcode(s) [15] 18355 0
6000 - Perth
Recruitment postcode(s) [16] 18354 0
6009 - Nedlands
Recruitment postcode(s) [17] 18353 0
7250 - Launceston
Recruitment outside Australia
Country [1] 9442 0
New Zealand
State/province [1] 9442 0
Wellington
Country [2] 9443 0
Singapore
State/province [2] 9443 0
Singapore

Funding & Sponsors
Funding source category [1] 313 0
Commercial sector/Industry
Name [1] 313 0
Novartis Australia
Country [1] 313 0
Australia
Funding source category [2] 314 0
Charities/Societies/Foundations
Name [2] 314 0
EORTC
Country [2] 314 0
Belgium
Primary sponsor type
Commercial sector/Industry
Name
Novartis Australia
Address
54 Waterloo Road North Ryde NSW 2113
Country
Australia
Secondary sponsor category [1] 244 0
Charities/Societies/Foundations
Name [1] 244 0
EORTC
Address [1] 244 0
AISBL / IVZW Avenue Mounierlaan, 83/11. Brussel 1200 Bruxelles, Belgie Belgique
Country [1] 244 0
Belgium
Other collaborator category [1] 279871 0
Other Collaborative groups
Name [1] 279871 0
Australasian Gastro-Intestinal Trials Group
Address [1] 279871 0
Level 6
The Chris O'Brien Lifehouse
119-146 Missenden Rd
Camperdown 2050
Country [1] 279871 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 1186 0
University of Sydney HREC
Ethics committee address [1] 1186 0
Ethics committee country [1] 1186 0
Australia
Date submitted for ethics approval [1] 1186 0
Approval date [1] 1186 0
11/05/2001
Ethics approval number [1] 1186 0
Ethics committee name [2] 1187 0
Royal North Shore
Ethics committee address [2] 1187 0
Ethics committee country [2] 1187 0
Australia
Date submitted for ethics approval [2] 1187 0
Approval date [2] 1187 0
Ethics approval number [2] 1187 0
Ethics committee name [3] 1188 0
Westmead
Ethics committee address [3] 1188 0
Ethics committee country [3] 1188 0
Australia
Date submitted for ethics approval [3] 1188 0
Approval date [3] 1188 0
Ethics approval number [3] 1188 0
Ethics committee name [4] 1189 0
Prince of Wales
Ethics committee address [4] 1189 0
Ethics committee country [4] 1189 0
Australia
Date submitted for ethics approval [4] 1189 0
Approval date [4] 1189 0
Ethics approval number [4] 1189 0
Ethics committee name [5] 1190 0
St George
Ethics committee address [5] 1190 0
Ethics committee country [5] 1190 0
Australia
Date submitted for ethics approval [5] 1190 0
Approval date [5] 1190 0
Ethics approval number [5] 1190 0
Ethics committee name [6] 1191 0
Bankstown-Lidcombe
Ethics committee address [6] 1191 0
Ethics committee country [6] 1191 0
Australia
Date submitted for ethics approval [6] 1191 0
Approval date [6] 1191 0
Ethics approval number [6] 1191 0
Ethics committee name [7] 1192 0
Peter MacCallum
Ethics committee address [7] 1192 0
Ethics committee country [7] 1192 0
Australia
Date submitted for ethics approval [7] 1192 0
Approval date [7] 1192 0
Ethics approval number [7] 1192 0
Ethics committee name [8] 1193 0
Geelong
Ethics committee address [8] 1193 0
Ethics committee country [8] 1193 0
Australia
Date submitted for ethics approval [8] 1193 0
Approval date [8] 1193 0
Ethics approval number [8] 1193 0
Ethics committee name [9] 1194 0
Western General
Ethics committee address [9] 1194 0
Ethics committee country [9] 1194 0
Australia
Date submitted for ethics approval [9] 1194 0
Approval date [9] 1194 0
Ethics approval number [9] 1194 0
Ethics committee name [10] 1195 0
Royal Brisbane
Ethics committee address [10] 1195 0
Ethics committee country [10] 1195 0
Australia
Date submitted for ethics approval [10] 1195 0
Approval date [10] 1195 0
Ethics approval number [10] 1195 0
Ethics committee name [11] 1196 0
Princess Alexandra
Ethics committee address [11] 1196 0
Ethics committee country [11] 1196 0
Australia
Date submitted for ethics approval [11] 1196 0
Approval date [11] 1196 0
Ethics approval number [11] 1196 0
Ethics committee name [12] 1197 0
Wesley Medical Centre
Ethics committee address [12] 1197 0
Ethics committee country [12] 1197 0
Australia
Date submitted for ethics approval [12] 1197 0
Approval date [12] 1197 0
Ethics approval number [12] 1197 0
Ethics committee name [13] 1198 0
Ashford Medical Centre
Ethics committee address [13] 1198 0
Ethics committee country [13] 1198 0
Australia
Date submitted for ethics approval [13] 1198 0
Approval date [13] 1198 0
Ethics approval number [13] 1198 0
Ethics committee name [14] 1199 0
Sir Charles Gairdner
Ethics committee address [14] 1199 0
Ethics committee country [14] 1199 0
Australia
Date submitted for ethics approval [14] 1199 0
Approval date [14] 1199 0
Ethics approval number [14] 1199 0
Ethics committee name [15] 1200 0
Royal Perth
Ethics committee address [15] 1200 0
Ethics committee country [15] 1200 0
Australia
Date submitted for ethics approval [15] 1200 0
Approval date [15] 1200 0
Ethics approval number [15] 1200 0
Ethics committee name [16] 1201 0
Launceston General
Ethics committee address [16] 1201 0
Ethics committee country [16] 1201 0
Australia
Date submitted for ethics approval [16] 1201 0
Approval date [16] 1201 0
Ethics approval number [16] 1201 0
Ethics committee name [17] 299252 0
Royal Prince Alfred Hospital HREC
Ethics committee address [17] 299252 0
Missenden Rd
Camperdown NSW
Ethics committee country [17] 299252 0
Australia
Date submitted for ethics approval [17] 299252 0
Approval date [17] 299252 0
31/05/2001
Ethics approval number [17] 299252 0

Summary
Brief summary
This is a randomised, open label, multicentre clinical trial of two different doses of imatinib to test whether there is any difference in disease outcome between the doses in patients with unresectable or metastatic malignant gastrointestinal stromal tumours (GIST). Recruitment opened in 2001, closed in 2002 with 946 patients worldwide and 116 at Australian, NZ and Singapore sites. Long term Follow UP closed October 2016.
Trial website
Trial related presentations / publications
1. Verweij J, Casali P, Zalcberg J, Le Cesne A, Reichardt P, Blay J-Y, Issels R, van Oosterom A, Hogendoorn P, van Glabbeke M, Judson I, Bertulli R, Judson I, for the EORTC Soft Tissue and Bone Sarcoma Group, the Italian Sarcoma Group and the Australian Gastro-intestinal trials group: Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet 2004; 364: 1127–1134.

2. Zalcberg J, Verweij J, Casali P, Le Cesne A, Reichardt P, Blay J, Schlemmer M, Van Glabbeke M, Brown M, Judson I, EORTC Soft Tissue and Bone Sarcoma Group tISGAG-ITG. Outcome of patients with advanced gastro-intestinal stromal tumours crossing over to a daily imatinib dose of 800 mg after progression on 400 mg. European Journal of Cancer 2005; 41(12): 1751-1757.
3. Van Glabbeke M, Verweij J, Casali P, Le Cesne A, Hohenberger P, Ray-Coquard I, Schlemmer M, van Oosterom A, Goldstein D, Sciot R, Hogendoorn P, Brown M, Bertulli R, Judson I. Initial and late resistance to imatinib in advanced gastrointestinal stromal tumors are predicted by different prognostic factors: a European Organisation for Research and Treatment of Cancer-Italian Sarcoma Group–Australasian Gastro-Intestinal Trials Group Study. Journal of Clinical Oncology 2005; 23(24): 5795-5804.
4. Goldstein D, Tan B, Rossleigh M, Haindl W, Walker B, Dixon J. Gastrointestinal stromal tumours: correlation of F-18-FDG gamma camera-based coincidence positron emission tomography with CT for the assessment of treatment respons--an AGITG study. Oncology 2005; 69(4): 326-332.
5. Van Glabbeke M, Verweij J, Casali PG, Simes J, Cesne AL, Reichardt P, Issels R, Judson IR, van Oosterom AT, Blay JY. Predicting toxicities for patients with advanced gastrointestinal stromal tumours treated with imatinib: a study of the European Organisation for Research and Treatment of Cancer, the Italian Sarcoma Group, and the Australasian Gastro-Intestinal Trials Group (EORTC- IS G-AGITG). European Journal of Cancer 2006; 42(14): 2277–2285.
6. Tamborini E, Bonadiman L, Greco A, Albertini V, Negri T, Gronchi A, Bertulli R, Colecchia M, Casali P, Pierotti M, Pilotti S. A new mutation in the KIT ATP pocket causes acquired resistance to imatinib in a gastrointestinal stromal tumor patient. Gastroenterology 2004; 127(1): 294–299.
7. Debiec-Rychter M, Sciot R, Le Cesne A, Schlemmer M, Hohenberger P, van Oosterom AT, Blay JY, Leyvraz S, Stul M, Casali PG, Zalcberg J, Verweij J, Van Glabbeke M, Hagemeijer A, Judson I; On behalf of the EORTC Soft Tissue and Bone Sarcoma Group, The Italian Sarcoma Group and the Australasian Gastro-Intestinal Trials Group. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. European Journal of Cancer 2006; 42(8): 1093–103.
8. Verweij J, Casali PG, Kotasek D, LeCesne A, Reichard P, Judson IR, Issels R, Van Oosterom AT, Van Glabbeke M, Blay J-Y. Imatinib does not induce cardiac left ventricular failure in gastrointestinal stromal tumours patients: analysis of EORTC-ISG-AGITG study 62005. European Journal of Cancer 2007; 43: 974–978.
9. Romeo S, Debiec-Rychter M, Van Glabbeke M, Van Paassen H, Comite P, Van Eijk R, Oosting J, Verweij J, Terrier P, Schneider U, Sciot R, Blay J, Hogendoorn P, on behalf of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Cell cycle/apoptosis molecule expression correlates with imatinib response in patients with advanced gastrointestinal stromal tumors. Clinical Cancer Research 2009; 15(12): 4191-4198.
10. Le Cesne A, Van Glabbeke M, Verweij J, Casali PG, Findlay M, Reichardt P, Issels R, Judson I, Schoffski P, Leyvraz S, Bui B, Hogendoorn PC, Sciot R, Blay JY. Absence of progression as assessed by response evaluation criteria in solid tumors predicts survival in advanced GI stromal tumors treated with imatinib mesylate: the Intergroup EORTC-ISG-AGITG phase III trial. Journal of Clinical Oncology 2009;27(24): 3969–3974. Published online 20 Jul 2009.
12. MetaGIST: Gastrointestinal Stromal Tumor Meta-Analysis Group, Verweij J, Blay J, Debiec-Rychter M, Demetri G, Heinrich M, Borden E, Blanke C, Crowley J, Rankin C, Casali P, Von Mehren M, Fletcher C, Fletcher J, Owzar K, Zalcberg J, Simes J, Bramwell V. Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: a meta-analysis of 1640 patients. Journal of Clinical Oncology 2010; 28(7): 1247–1253
13. Hohenberger P, Bonvalot S, Litiere S, Rutkowski P, van Coevorden F, Meeus P, Marréaud S, Raventos VA, Kotasek D, Padbury R, Van der Graaf W, Gronchi A. Surgical resection of metastatic GIST on imatinib delays recurrence and death: results of a cross-match comparison in the EORTC intergroup study 62005, aimed at assessing the clinical activity of imatinib at two dose levels in patients with unresectable or metastatic GIST Connective Tissue Oncology Society; 15–18 Oct 2014; Berlin.
14. Lee CK, Goldstein D, Gibbs E, Joensuu H, Zalcberg J, Verweij J, Casali PG, Maki RG, Cioffi A, McArthur G, Lord SJ, Yip D, Kanjanapan Y, Rutkowski P. Development and validation of prognostic nomograms for metastatic gastrointestinal stromal tumour treated with imatinib. European Journal of Cancer. Published online 25 Mar 2015
15. Current JCO Casali PG, Zalcberg J, Le Cesne A, Reichardt P, Blay J-Y, Lindner L, Judson I, Schöffski P, Bauer J, Italiano A, Grünwald V, Lopez Pousa A, Kotasek D, Sleijfer S, Kerst JM, Rutkowski P, Fumagalli E, Hogendoorn PCW, Litière S, Marreaud S, Van der Graaf W, Gronchi A, Verweij, on behalf of EORTC STBSG, ISG, AGITG. Ten-year progression-free and overall survival in patients with unresectable or metastatic gastrointestinal stromal tumours (GIST). Long-term analysis of the EORTC, ISG, AGITG intergroup Phase III randomized trial on imatinib at two dose levels. Accepted JCO October 2016
Public notes

Contacts
Principal investigator
Name 35434 0
Prof John Zalcberg
Address 35434 0
Department of Epidemiology and Preventative Medicine
School of Public Health
Monash University
The Alfred Centre
6/99 Commercial Rd
Melbourne VIC 3004
Country 35434 0
Australia
Phone 35434 0
+61 3 9903 0388
Fax 35434 0
Email 35434 0
[email protected]
Contact person for public queries
Name 9327 0
Advanced GIST trial coordinator
Address 9327 0
NHMRC Clinical Trials Centre
Locked Bag 77
Camperdown NSW 1450
Country 9327 0
Australia
Phone 9327 0
+61 2 9562 5000
Fax 9327 0
+61 2 95625094
Email 9327 0
[email protected]
Contact person for scientific queries
Name 255 0
Professor John Zalcberg
Address 255 0
School of Public Health
Monash University
The Alfred Centre
6/99 Commercial Rd
Melbourne VIC 3004
Country 255 0
Australia
Phone 255 0
+61 3 9903 0388
Fax 255 0
+61 3 9903 0556
Email 255 0
[email protected]

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