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)
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ClinicalTrials.gov Identifier: NCT02365441 |
Recruitment Status :
Active, not recruiting
First Posted : February 19, 2015
Last Update Posted : July 7, 2023
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Tracking Information | |||||||
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First Submitted Date ICMJE | November 4, 2014 | ||||||
First Posted Date ICMJE | February 19, 2015 | ||||||
Last Update Posted Date | July 7, 2023 | ||||||
Actual Study Start Date ICMJE | June 30, 2015 | ||||||
Estimated Primary Completion Date | December 31, 2023 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
Objective tumour response (complete or partial response) as determined by RECIST v1.1 [ Time Frame: At or before 9 months from the time from either (i) randomization (if patients have not yet commenced treatment) or (ii) commencement of therapy (if patients are randomized during the first cycle of imatinib) ] The objective tumour response rate (OTRR) will be calculated by summing the number of participants assessed as having a complete or partial response within the first 9 months from the time from either (i) randomization (if patients have not yet commenced treatment) or (ii) commencement of therapy (if patients are randomized during the first cycle of imatinib), and dividing this by the total number of participants evaluable for response. For patients who undergo surgery, the best response is determined in the time period that precedes the date of surgery. The responses are confirmed at the time of the next scheduled imaging, usually done 8 weeks after the first detection of response, provided that imaging of the target lesions is not indicated sooner than this for other reasons. Both the numbers and the proportions of confirmed and unconfirmed responses will be reported. The minimum duration of SD is defined as 8 weeks.
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Original Primary Outcome Measures ICMJE |
Progression free survival at 24 months (disease progression or death) [ Time Frame: 24 Months ] PFS at 24 months as calculated from the time from either (i) randomization if patients have not yet commenced treatment) or (ii) commencement of therapy (if patients are randomized during the first cycle of imatinib) to the date of progression as determined by RECIST v1.1
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Change History | |||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures |
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Original Other Pre-specified Outcome Measures | Same as current | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | A Randomised Trial of Imatinib Alternating With Regorafenib Compared to Imatinib Alone for the First Line Treatment of Advanced Gastrointestinal Stromal Tumour (GIST) | ||||||
Official Title ICMJE | A Randomised Phase II Trial of Imatinib Alternating With Regorafenib Compared to Imatinib Alone for the First Line Treatment of Advanced Gastrointestinal Stromal Tumour (GIST) | ||||||
Brief Summary | 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. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 2 | ||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Gastrointestinal Stromal Tumour | ||||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Active, not recruiting | ||||||
Actual Enrollment ICMJE |
78 | ||||||
Original Estimated Enrollment ICMJE |
240 | ||||||
Estimated Study Completion Date ICMJE | December 31, 2023 | ||||||
Estimated Primary Completion Date | December 31, 2023 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | Australia, Finland, France, Netherlands, Norway, Singapore, Slovakia, Spain, Sweden, United Kingdom | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT02365441 | ||||||
Other Study ID Numbers ICMJE | AG1013GST ACTRN12614000950662 ( Other Identifier: ANZCTR ) |
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Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product | Not Provided | ||||||
IPD Sharing Statement ICMJE | Not Provided | ||||||
Current Responsible Party | Australasian Gastro-Intestinal Trials Group | ||||||
Original Responsible Party | Same as current | ||||||
Current Study Sponsor ICMJE | Australasian Gastro-Intestinal Trials Group | ||||||
Original Study Sponsor ICMJE | Same as current | ||||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | Australasian Gastro-Intestinal Trials Group | ||||||
Verification Date | July 2023 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |