In this summary, we have highlighted recent clinical trials that are still recruiting in the U.S. which investigate potential treatments for GIST patients.
Our database, gisttrials.org, lists over 70 trials that are GIST-related which are ongoing around the world. Currently there are 11 GIST-related trials recruiting in the United States. (Of these 11, two are no Phase (0), three are Phase 1, five are Phase 2, one is Phase 1/2.) This article gives a sampling of four trials currently recruiting for KIT/PDGFRa mutant GIST, SDH-deficient GIST (2), and a no Phase Surgery trial for all GIST Types. For further information about GIST trials including international trials, visit: The Life Raft Group Clinical Trials Website.

 About Phase 1 trials

It is important to recognize that Phase I studies are held to find the highest dose of the new treatment that can be given safely without causing severe side effects.

• The first few people in the study get a very low dose of the treatment and are watched very closely. If there are only minor side effects, the next few participants get a higher dose. This process continues until doctors find a dose that’s most likely to be and effective treatment while having an acceptable level of side effects.

• Safety is the main concern. The research team monitors participants and watches for severe side effects. Due to the small numbers of people in Phase I studies, rare side effects may not be seen until later phases of the trial when more people are receiving the treatment.

• While some people may benefit from being on one, disease response is not the main purpose of a Phase I trial. Phase I trials carry the most potential risk, but these studies do help some patients. For those with life-threatening illnesses, weighing the potential risks and benefits carefully is key. Sometimes people choose
to join Phase I trials when all other treatment options have already been tried.

Phase I trials carry the most potential risk, but these studies do help some patients. For those with life-threatening illnesses, weighing the potential risks and benefits carefully is key. Sometimes people choose
to join Phase I trials when all other treatment options have already been tried.

For patients with advanced KIT/PDGFRa mutant GIST:

NB003 Phase 1“A Study of NB003 in Patients With Advanced Malignancies” 
Site is Memorial Sloan Kettering Cancer Center NY, NY.
Principal Investigator: Dr. Ping Chi. The trial started 8/6/2021. Dose escalation phase will be followed by
an expansion phase. Plans are to recruit 36 over a period of 20 months. NB003 oral tablets are administered twice daily for repeated 28-day cycles. 

Primary objectives are incidence of dose limiting toxicity and incidence of adverse events. Tumor sample collection is required. Includes GIST and other solid tumors with either KIT or PDGFRa mutations. Includes patients with advanced GIST who have progressed on or had an intolerability to imatinib and other standard of care (SoCs) or refused other SoCs.

Sponsor is Ningbo Newbay Technology Development Co., Ltd in China. Obtained development rights from AstraZeneca in 2020. NB003 was previously called AZD3229. AstraZeneca employee authors described AZD3229 translational relevance in a 2019 paper: “AZD3229 has potential as a best-in-class treatment for patients with GIST with mutations in KIT and PDGFRα, and this compound may overcome the limitations experienced with existing treatment options in the clinic which are limited by off-target effects leading to drug holidays and dose reductions leading to lack of optimum efficacy.” Contact at MSKCC, 646-888-3915
or email dastasj@mskcc.org  NCT04936178

For patients with SDH-deficient GIST

Temozolomide Phase 2“Temozolomide (TMZ) In Advanced Succinate Dehydrogenase (SDH) Mutant/Deficient Gastrointestinal Stromal Tumor (GIST)”.

Trial sites include University of California San Diego, University of Miami, Oregon Health Science University, Portland, Fox Chase Cancer Center, Philadelphia. Principal Investigators include Adam Burgoyne, Jon Trent, Mike Heinrich, Margaret von Mehren. Started 9/12/2018. 

Recruiting 23 participants over 48 months. Temozolomide (Temodar®) tablets taken orally once a day for 21 days followed by seven days off drug for each 28-day drug cycle. 

Primary objective is overall response rate. Patients will continue treatment until disease progression or unacceptable toxicity. Includes patients who have pathologically confirmed SDH-mutant/deficient GIST and tumors measurable on CT scans. 

Information concerning the rationale for use of Temozolomide in SDH-deficient GIST can be found in the following reports:

• 1/7/2019 – “Preferential MGMT methylation could predispose a subset of KIT/PDGFRA-WT GISTs, including SDH-deficient ones, to respond to alkylating agents”

• 10/12/2020 – “Abnormal MGMT Promoter Methylation in Gastrointestinal Stromal Tumors: Genetic Susceptibility and Association with Clinical Outcome

Information concerning side effects of TMZ in GIST patients can be found in the following report:

• 12/4/2003 – “A two-arm phase II study of temozolomide in patients with advanced gastrointestinal stromal tumors and other soft tissue sarcomas”.

Sponsor is Dr. Adam Burgoyne. Contact at UCSD at 858-822-3092 or email aburgoyne@ucsd.edu NCT03556384

Rogaratinib Phase 2“Testing the Anti-cancer Drug, Rogaratinib (BAY 1163877), for Treatment of Advanced Sarcoma With Alteration in Fibroblast Growth Factor Receptor (FGFR 1-4), and in Patients With SDH-deficient Gastrointestinal Stromal Tumor (GIST)” 

Trial sites include: Dana-Farber Boston, Boston, The National Cancer Institute Bethesda, City of Hope Duarte, CA, Memorial Sloan Kettering New York, NY, Washington University School of Medicine St. Louis, University of Pittsburgh Cancer Institute.

Principal Investigators include: Suzanne George, A. P. Chen, Mark Agulnik, Katherine Thornton, Brian Van Tine, Melissa Burgess. Started 2/1/2021. 

Recruiting 48 participants over 24 months. Patients take Rogaratinib pills twice daily on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. 

Primary objective is to estimate the objective radiographic response rate. Serial biopsies may be required. Confirmed SDH-deficient patients must have measurable disease on scans. The sponsor is the National Cancer Institute. 

The rationale for targeting FGFR in SDH-deficient GIST is provided in the following paper: 

• 10/16/2019 – “Altered chromosomal topology drives oncogenic programs in SDH-deficient GISTs”
Information about the safety and side effects of Rogaratenib is provided in the following paper reporting results of a Phase 1 dose escalation study:

• 8/9/2019 – “Rogaratinib in patients with advanced cancers selected by FGFR mRNA expression: a phase 1 dose-escalation and
dose-expansion study.”

Contact information is available for each site at clinicaltrials.gov  NCT04595747

For all GIST patients:

Surgery, No Phase“Surgery in Gastrointestinal Stromal Tumors (GISTs)
for Treatment, Tumor Modeling, and Genomic Analysis”


National Institute of Health Clinical Center in Bethesda, MD. 

Principal Investigator is Dr. Andrew M Blakely. Started 12/18/2020. Recruiting 400 participants over 20 years. Participants will be monitored every 6-12 months at the NIH Clinical Center, for up to 10 years before having surgery. If they need surgery, it will be performed at the NIH. Then, they will be monitored every 6-12 months, for up to five years after surgery.

If a participant has surgery, tumor tissue samples will be taken. If a participant does not need surgery, their participation will end after 10 years. If they have surgery, the five-year monitoring period will restart after each surgery. 

The overall objective is to follow people with GISTs and collect tumor tissue so that it can be studied in the lab. The Primary objective is to evaluate and follow patients with GISTs, particularly WT or treatment-refractory non-WT, to support translational research for this rare disease Time Frame: on-going. People aged six and older who have GIST are eligible. 

Inclusion criteria include: Histological confirmation or clinical presentation suspicious of GIST; histological confirmation will be preferably by review of archival tissue if available, fresh biopsy will not be required if inadequate tissue sample. 

Sponsor is the National Cancer Institute. Contact: Audra A Satterwhite, R.N. at 240-858-3552 or email audra.satterwhite@nih.gov  NCT04557969 

This trial is further described on the LRG website:
https://liferaftgroup.org/2021/06/its-time-11-rare-subsets-clinical-trials/

Please discuss these trials with your GIST expert to determine which, if any, are appropriate for you.

For more information on clinical trial phases:
https://www.cancer.org/treatment/treatments-and-side-effects/clinical-trials/what-you-need-to-know/phases-of-clinical-trials.html & this video What GISTers Need to Know About Clinical Trials.

Contact the LRG for more information on GIST clinical trials at: liferaft@liferaftgroup.org

Read December 2021 newsletter