TRIAL DETAIL

A Randomised Trial of Imatinib Alternating With Regorafenib Compared to Imatinib Alone for the First Line Treatment of Advanced Gastrointestinal Stromal Tumour (GIST) (ALT GIST)

Drug:
Trial Name:
A Randomised Trial of Imatinib Alternating With Regorafenib Compared to Imatinib Alone for the First Line Treatment of Advanced Gastrointestinal Stromal Tumour (GIST) (ALT GIST)
NCT#:
Conditions:
Gastrointestinal Stromal Tumor
Status:
Recruiting
Phase:
2
Start Date 02/01/2015
Age of Trial (yrs) 5.5
Treatment Phase:
First-line
Drug Category:
KIT/PDGFRA inhibitor + VEGF inhibitor
Strategy:
Trial Type:
Specifically GIST and only GIST
Other Protocol IDs:
AG1013GST, ACTRN12614000950662
Sponsor:
Australasian Gastro-Intestinal Trials Group
Patient Contact:
ALT GIST coordinator 02 9562 5000 altgist@ctc.usyd.edu.au
Contact email:
Contact Phone:
Randomized:
Randomized
IV or Oral:
Oral
Trial Notes:
An open label randomised trial for adults with histologically confirmed measurable metastatic GIST who have received no other treatment for metastatic disease. The study aims to determine if an alternating regimen of imatinib and regorafenib has sufficient activity and safety in comparison to imatinib alone to warrant further evaluation as a first line treatment for metastatic GIST.

Detailed Description:

PROTOCOL SYNOPSIS Background Despite highly active current treatment for metastatic gastrointestinal stromal tumour (GIST) with the use of imatinib, most people will ultimately relapse and die of multifocal metastatic disease. Using an alternating regimen of imatinib and regorafenib with brief drug free intervals may allow tumour stem cells to re-enter the cell cycle and become susceptible once more to drug therapy. Regorafenib, a multi-targeted tyrosine kinase inhibitor (TKI) with activity against angiogenic, stromal and oncogenic receptor tyrosine kinases, has demonstrated activity in the treatment of GIST and is FDA approved for third line therapy of advanced GIST.

General aim To determine if an alternating regimen of imatinib and regorafenib has sufficient activity and safety to warrant further evaluation as a first line treatment for metastatic GIST.

Design Prospective, randomised, open label phase II trial, stratified by participating site, previous adjuvant therapy (prior vs none), and previous imatinib for metastatic disease for less than 21 days.

Population The target population is adults with histologically confirmed, measurable metastatic GIST, who have received no prior treatment for metastatic disease. Patients who are currently taking, and have had up to 21 days of uninterrupted treatment with 400mg daily of imatinib are eligible to participate in this study.

Study treatments

Patients will be randomised to receive either:

Arm A - imatinib 400mg orally daily continuously (control arm); or Arm B - alternating 28-day periods of imatinib 400mg orally daily for 21 to 25 days followed by a washout (drug free) period of 3 to 7 days, then regorafenib 160mg orally daily for 3 weeks followed by a 7 day washout (drug free) period.

Treatment will continue until disease progression or prohibitive adverse events as detailed in the protocol.

Statistical considerations In order to demonstrate a relative increase in progression free survival at 24 months from the date of randomisation from an expected 78% to 88%, with 80% power and 95% confidence based on A'Hern's adjustment to Fleming's design, approximately 110 evaluable participants will be required in each arm. Thus, it is proposed to enrol 240 participants into the trial, allowing for approximately a 10% drop-out rate. Currently 80% of participants are expected to achieve a clinical benefit at 24 months (CBR - rate of complete or partial response, or stable disease). A secondary outcome would be to determine whether a minimum 25% relative increase of the CBR (from 80% to 85%) in the experimental cohort can be attained. The study will be open to recruitment for 36 months while follow-up will continue until the last enrolled participant has been followed for a minimum of 24 months timed from the date of commencement of treatment.

Trial Links

 
 
 
 

Trial Results

 

Drug Information

See imatinib
 
See regorafenib
 
ALT GIST opens first Australian site
 

Trial Sites

Name
Address
City
State
Zip
Country
Edith Street
Waratah
New South Wales
2298
Australia
Barker Street
Randwick
New South Wales
2031
Australia
199 Ipswich Road
Woolloongabba
Queensland
4102
Australia
520 South Road
Kurrulta Park
South Australia
5037
Australia
Flinders Drive
Bedford Park
South Australia
5042
Australia
Yamba Drive
Garran
Australian Capital Territory
2605
Australia
Hospital Avenue
Nedlands
Western Australia
6009
Australia
24 Campbell Street
Hobart
Tasmania
7001
Australia
69 Nordsvan Drive
Wodonga
Victoria
3690
Australia
Frankston-Flinders Road
Frankston
Victoria
3199
Australia
Oslo
N-0310
Norway
Singapore
Singapore
Helsinki
FIN-00029
Finland
229 Cours Argonne
Bordeaux
Gironde
33076
France
Dijon
France
28 rue Laennec
Lyon
Rhone
69373
France
Villejuif
Val de Narne
94805
France
Amsterdam
Netherlands
Bergen
N-5021
Norway
Lund
SE-221 85
Sweden
Barcelona
Spain
Bratislava
NSW
Slovakia
197 Fulham Rd.
London
SW3 6JJ
UK
Birmingham
UK
Nottingham
UK