• ALT GIST
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Trial Status

In Follow-up

Cancer Type

GIST

Protocol Title

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)

Purpose of the Study

The aim of this study is to determine whether an alternating regimen of Imatinib and Regorafenib improves disease control in patients with metastatic GIST. The primary objective for the study is progression free survival at 24 months. Secondary objectives include objective tumour response rate, clinical benefit rate, complete response rate, time-to-treatment failure, safety/toxicity/tolerability and overall survival.

ELIGIBILITY CRITERIA

Inclusion Criteria

  1. Adults (over 18 yrs) with histologically confirmed GIST.
  2. Unresectable, metastatic disease.
  3. No prior TKI for metastatic disease.
  4. Adequate bone marrow function
  5. Tumour tissue available for central review.
  6. Willing and able to comply with all study requirements, including treatment timing and/or nature of required assessments.
  7. Study treatment both planned and able to start within 14 days of randomisation.
  8. Signed, written informed consent.

Exclusion Criteria

  1. Concurrent GI illness which may prevent absorption of imatinib or regorafenib.
  2. Use of other investigational drugs within 4 weeks prior to enrolment.
  3. Known sensitivity to any of the study drugs, study drug classes, or excipients in the formulation.
  4. Presence of brain metastases.
  5. Inability to swallow tablets.
  6. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomisation.
  7. Active hepatitis B or C or HIV, or chronic hepatitis B or C requiring treatment with antiviral therapy.
  8. Interstitial lung disease with ongoing signs and symptoms.
  9. Other significant medical or psychiatric condition judged by the investigator to interfere with protocol requirements.
  10. History of another malignancy within 5 years prior to registration.
  11. Pregnancy, lactation, or inadequate contraception.

CONTACT EMAIL

altgist@ctc.usyd.edu.au

PRINCIPAL INVESTIGATOR

Professor Desmond Yip

DETAILED INFORMATION AVAILABLE

Available online at the Australian New Zealand Clinical Trial Registry (ANZCTR) here.

Funding

Bayer Global

Participating Centres

Australian Capital Territory
Canberra Hospital
New South Wales
Lake Macquarie Private Hospital
Prince of Wales Hospital
Bankstown-Lidcombe Hospital
Calvary Mater- Newcastle
The Tweed Hospital
Border Medical Oncology
Queensland
Princess Alexandra Hospital
South Australia
Flinders Medical Centre
Ashford Cancer Centre
Tasmania
Royal Hobart Hospital
Victoria
Peninsula & South East Oncology
Western Australia
Sir Charles Gairdner Hospital
Singapore
NCCS Singapore
United Kingdom
UCL Hospital
Nottingham City Hospital
University Hospital Birmingham-Queen Elizabeth Hospital
Royal Marsden Hospital – London
St James Hospital – Leeds
Beatson West of Scotland Cancer Centre
Europe
Netherlands Cancer Institute-Antoni Van Leeuwenhoek
Leiden University Medical Center, The Netherlands
University Medical Center Groningen, The Netherlands
Institut Bergonie
Centre Leon Berrard
Institute Gustave Roussy
Centre Georges-Francois-Leclerc
ICO L’Hospitaltt-Hospital Duran I Reynals (Institut Catala D’Oncologia)
National Cancer Institute-Slovakia
Instituto Oncologico Veneto, Italy
Scandinavia
The Norwegian Radium Hospital
Haukeland University Hospital, Bergen
Helsinki University Hospital, Helsinki
Tampere University Hospital, Finland
Lund University Hospital
Sahlgrenska University Hospital, Gotherburg
Oulu University Hospital, Finland

Trial Status

In Follow-up

Cancer Type

GIST

Protocol Title

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)

Aim

The aim of this study is to determine whether an alternating regimen of Imatinib and Regorafenib improves disease control in patients with metastatic GIST. The primary objective for the study is progression free survival at 24 months. Secondary objectives include objective tumour response rate, clinical benefit rate, complete response rate, time-to-treatment failure, safety/toxicity/tolerability and overall survival.

Background

ALT GIST is a randomised Phase II designed to determine whether an alternating Imatinib and Regorafenib treatment plan will be effective in stopping drug resistance in patients with advanced GIST.

Currently, the standard first line treatment for unresectable GIST is continuous treatment with Imatinib. However, in almost all cases the cancer will develop resistance to the drug. One possible cellular mechanism behind this resistance is that after continual exposure to the drug, GIST cells develop changes in their growth pathways that allow them to eventually become unaffected by the medication. The purpose of ALT GIST is to alternate Imatinib with a second drug called Regorafenib, which has been found to display efficacy in delaying the progression of cancer. 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.

If the alternating treatment is found to be beneficial and tolerable, it would be further studied in a Phase III trial.

Clinical Trial Design

ALT GIST is a randomised Phase II trial designed to investigate effectiveness and activity by alternating the medications: Imatinib and Regorafenib.

Participants will be randomly allocated to one of two groups. Participants will either be treated continuously with Imatinib (control group) or receive alternating treatment with Imatinib and Regorafenib.

For a single cycle of study treatment in the experimental arm, an Imatinib (400mg) tablet will be taken orally for 21 to 25 days followed by a 3 to 7-day gap when there will be no medication. In total, the days taking Imatinib plus the period without medication must be 28 days. This is followed by 21 days of Regorafenib (40mg), which will be taken as 4 tablets daily, and a 7-day gap without medication.

The control group will be given a regimen of continuous Imatinib in a 56-day cycle.  For both groups treatment will continue until progressive disease or unacceptable toxicity. A drug administration diary will be provided to all participants to record their intake and progress.

For the first 12 months, CT scans every 8 weeks will evaluate the effectiveness of the treatment. After the initial 12 months of the trial, the CT scans will be performed every 12 weeks and continue until there is cancer progression.

Participants will be regularly monitored for a minimum of 24 months follow-up in order to determine whether the alternating treatment approach improves disease control. If it is found to have benefit and be tolerable, this alternating approach will be further evaluated in a larger study.

Participating Centres

Australian Capital Territory
Canberra Hospital
New South Wales
Lake Macquarie Private Hospital
Prince of Wales Hospital
Bankstown-Lidcombe Hospital
Calvary Mater- Newcastle
The Tweed Hospital
Border Medical Oncology
Queensland
Princess Alexandra Hospital
South Australia
Flinders Medical Centre
Ashford Cancer Centre
Tasmania
Royal Hobart Hospital
Victoria
Peninsula & South East Oncology
Western Australia
Sir Charles Gairdner Hospital
Singapore
NCCS Singapore
United Kingdom
UCL Hospital
Nottingham City Hospital
University Hospital Birmingham-Queen Elizabeth Hospital
Royal Marsden Hospital – London
St James Hospital – Leeds
Beatson West of Scotland Cancer Centre
Europe
Netherlands Cancer Institute-Antoni Van Leeuwenhoek
Leiden University Medical Center, The Netherlands
University Medical Center Groningen, The Netherlands
Institut Bergonie
Centre Leon Berrard
Institute Gustave Roussy
Centre Georges-Francois-Leclerc
ICO L’Hospitaltt-Hospital Duran I Reynals (Institut Catala D’Oncologia)
National Cancer Institute-Slovakia
Instituto Oncologico Veneto, Italy
Scandinavia
The Norwegian Radium Hospital
Haukeland University Hospital, Bergen
Helsinki University Hospital, Helsinki
Tampere University Hospital, Finland
Lund University Hospital
Sahlgrenska University Hospital, Gotherburg
Oulu University Hospital, Finland

Contact Email

altgist@ctc.usyd.edu.au

Principal Investigator

Professor Desmond Yip (The Canberra Hospital, Woden ACT)

More Information

Available online at the Australian New Zealand Clinical Trial Registry (ANZCTR) here.

Funding

Bayer Global