Clinical Trials and Research
Research into GIST is moving very fast, and we now know very much more than we did ten years ago. However there are still many questions unanswered:
- We DO know that most GIST tumours have mutations in the KIT or PDGFRA genes, and we know how to identify which exon these mutations are in.
- We DON'T know why some GISTs don't have mutations at these sites, the wild type GISTs. (Presumably they have mutations in other locations.)
- We DON'T know why paediatric GIST behaves differently from adult GIST.
- We DON'T know why GISTs with mutations in different exons react differently to Glivec and Sutent.
- We DON'T know why some GISTs behave more aggressively than others, even if they have the same mutations.
- We DON'T know whether all patients need the same dose of Glivec or Sutent in order to get the same concentration in the blood.
Current research is trying to find answers to some of these questions, as well as continuing to search for new drugs or combinations of drugs which will offer patients total long-term remission or a cure.
There is a very good booklet called Understanding Clinical Trials produced by UK Cancer Research Collaboration UKCRC www.ukcrc.org. This explains the terms you may hear, like placebo, control arm etc. If you are invited to enroll in a trial, this is recommended background reading.
National GIST Guidelines...
UK clinical practice guidelines for the management of gastrointestinal stromal tumours (GIST) 2017
We are delighted to announce that the UK National clinical practice guidelines for GIST have been updated and published and can be accessed via this link ...
Trials Relevant to GIST - 2018/19
The Intrigue Study
The INTRIGUE Phase 3 study of ripretinib is now open to enroll second-line GIST patients, regardless of their mutational status, who have progressed on, or are intolerant to front-line therapy with imatinib.
The following links provide more information:
Clinicaltrials.gov (this link shows the study locations)
Businesswire.com (this link provides more information about the trial)
Please contact any of the following to register for this trial:
- Dr Robin Jones at the Royal Marsden in London
- Dr Palma Dileo at the University College Hospital in London
- Dr Robin Young at the Sheffield Teaching Hospitals NHS Trust
The Invictus trial
Testing DCC-2618 in patients with advanced GIST who have been treated with other anticancer therapies – incl. imatinib, sunitinib, regorafenib – before.
Eligible patients are those Patients with confirmed advanced or metastatic GIST with all types of mutation in KIT or PDGFRa (excluded are patients without KIT or PDGFRa mutations) Patients must have progressed on imatinib, sunitinib, and regorafenib or do not tolerate any of these treatments.
This link provides more information.
Please contact Dr Robin Jones at the Royal Marsden Hospital in London to register for this trial.
The Voyager trial
Avapritinib vs Regorafenib in unresectable or metastatic GIST.
A Phase 3 study in patients with locally advanced unresectable or metastatic GIST (advanced GIST) of avapritinib versus regorafenib in patients previously treated with imatinib and 1 or 2 other tyrosine kinase inhibitors (TKIs).
This link provides more information as do these https://www.clinicaltrials.gov/ct2/show/NCT03465722
Please contact the following hospitals to register for this trial:
- Glasgow - Beatson West of Scotland Cancer Centre
- Sheffield - Sheffield Teaching Hospitals NHS Foundation Trust - Dr Robin Young
- London - Guys Hospital
- London - The Royal Marsden Hospital - Dr Robin Jones
This Phase 1 clinical trial is now recruiting patients with second-line GIST. At the time of writing (October 2018) there are about 20 or so slots available in this second-line GIST patient cohort. Note this study has additional patient cohorts for PDGFRα D842V-driven GIST and third-line or later GIST, but these are now fully enrolled.
More information about the Navigator trial is available at https://www.clinicaltrials.gov/ct2/show/NCT02508532.
This trial is open at the Royal Marsden Hospital, London - Dr Robin Jones
The Scandinavian 3 versus 5 years adjuvant imatinib study is:
Open at the following centres and recruitment has been extended until 31st March 2020:
- Addenbrookes Hospital, Cambridge (Please contact Dr Ramesh Bulusu)
- The Royal Marsden, London (Please contact Dr Robin Jonnes)
- University College Hospital, London (Please contact Dr Palma Dileo)
- Beatson (West of Scotland Cancer centre), Glasgow (Please contact Dr Jeff White)
- Weston Park Hospital, Sheffield (Please contact Dr Robin Young)
- Queen Elizabeth Hospital, Birmingham (Please contact Dr Mariam Jafri)
- Nottingham University Hospital (Please contact Dr Ivo Hennig)
- The Christie Hospital, Manchester (Please contact Dr Michael Leahy)
The CABOGIST Trial
The EORTC CABOGIST study for cabozantinib for relapsed metastatic GIST.
This link takes you to a Liferaft group report about this drug and GIST.
Please contact Dr Charlotte Benson at the Royal Marsden Hospital to register for this trial.
'BLU-285-1101' - A Study of BLU-285 in Patients with Gastrointestinal Stromal Tumors (GIST) and other Relapsed and Refractory Solid Tumors
Dr Robin Jones has the BLU285 GIST study open at the Royal Marsden. To register for this trial pleas contact Dr Jones.
This link takes you to the news released late in 2016 about the Phase 1 trial results...
Trials opened pre December 2016
'ALT' GIST Trial now open! -
A new first line metastatic GIST trial called ‘Alt GIST’ is now open at the Royal Marsden Hospital in London.
This is a randomised Phase II trial being run through the EORTC (European Organisation for Research and Treatment of Cancer) and is comparing standard imatinib treatment with imatinib and regorafenib alternating monthly.
Eligible patients are those with metastatic GIST who have had no previous drug treatment or patients who have been started on imatinib for 3 weeks or less.
Centres in the UK that will be opening include:
- The Royal Marsden - London (lead site)
- UCLH - London
- The Christie Manchester
To register for this trial patients will need to be referred by their oncologist to closest centre listed above.
The biotech company that is developing this drug have initiated both first and second line trials for GIST. This means that if you are about to start treatment with Imatinib or Sunitinib then you may be offered the opportunity to enter one of these trials. If you are being treated in a hospital that is not listed below and are interested in participating then your clinician can connect you to the relevant clinicians.Masitinib is a tyrosine kinase inhibitor similar to imatinib and sunitinib but with a slightly different profile. The 1st line trial is a direct head to head randomised trial of imatinib v masitinib. This means that patients who enrol will not be aware which drug they are receiving however should the trial centre feel that the patient is not responding then the patient will be unblended and have the option of conventional GIST treatment. Similarly the 2nd line trial is head to head of sunitinib v masitinib and the same criteria as above will enable the patient to receive conventional treatment should there be no benefit. There are a number of trial centres in the UK who have already signed up (with more to come). Centres who have signed up to-date for the 1st line trial (imatinib v masitinib) are:
- Dr Marples in Leeds
- Dr Leahy at the Christie
- Dr Hayward in Edinburgh
- Dr Sivamarlingam in Preston
- Dr Morgan in Cardiff
- Dr Ali in Clatterbridge
For the 2nd line trial the following centres have signed up so far:
- Dr Morgan Cardiff
- Dr Hickish Bournmouth
- Dr Leahy Christie
We are trying to get updated information on the completed phase 2 trials for both of these trials and will hopefully be able to give an update at our 2016 patient meeting in Nottingham and also post information on Listserve.
This is a pan-European project exploring new ways of treating metastatic GIST. For more information go to www.mitigate-project.eu/about/mitigate-for-patients
Various Drug Trials
There are several trials trying to find out whether taking imatinib (Glivec) after complete removal of a GIST helps to prevent recurrence and long-term survival. This is called adjuvant treatment. (ie taking a drug when there is no obvious disease.)
One trial in the US has shown that taking imatinib for a year seems to dramatically increase the time before recurrence after surgery for Kit-positive high risk GIST. (Click here to download the full text of the NOVARTIS press release.) However it seems to make no difference to patients who had low risk GIST.
There are two other trials looking at adjuvant treatment. The pan-European adjuvant trial EORTC 62024 closed after recruiting 750 patients. Patients with a complete resection (no marginal disease or mets) were randomised to either 400mg imatinib for two years, or to no treatment (which is the standard care). The aim is to answer the question about whether imatinib has value in preventing recurrence and giving long-term survival. Unlike the US trial, the patients will be followed up for years, so we will have no results for a long time.
Another similar trial being conducted in Scandinavia is comparing the results of taking 400mgs per day of Glivec after surgery, for one year or three years.
These trials show that for high-risk patients taking imatinib for three years after surgery increases both time to progression and overall survival. Taking imatinib for one year was better than not taking it at all, but not as effective as taking it for three years. Many doctors now think that high-risk patients should take imatinib for ever, but the cost implications of this are significant (or at least until it goes off patent!). In the UK the adjuvant use of imatinib is not yet approved by NICE, but it is available in Scotland and also in parts of England and Wales through the Cancer Drugs Fund.
A trial of Regorafinib (made by Bayer) has shown very encouraging results. There are no trials in the Uk for this drug, but it has now become available via THE CANCER DRUGS FUND, after an appeal by GCUK. The use of Regorafinib for GIST is subject to review by NICE
Masitinib and AB Science (to be updated)
We are able to update you on the above new drug. An application has been submitted to the EMA (European Medicines Agency) for a conditional licence for masitinib in 2nd line GIST. It is expected that a decision will be made before the year end and this means that clinicians will be able to choose between sunitinib and masitinib for patients who have progressed on imatinib 400mg or 800mg. Based on the phase 2 trial results, (masitinib v sunitinib) there appears to be a benefit for patients who received masitinib.
There is also an on going phase 3 trial of Masitinib currently open and several UK hospitals are participating in the study although full results will not be available until 2015. Be aware that this trial has now closed. Click on this Cancer Research UK link for more details and suitability.
AB Science have also initiated a compassionate use programme in the UK, offering compassionate access to Mastinib (third line) for patients who have progressed on current licensed treatments (imatinib & sunitinib). This appears to be not widely known by all health care providers. We can put you in contact with the right people if you think this could help.
If you require further information please contact:
David Falconer Special Adviser GCUK: firstname.lastname@example.org