Gastrointestinal Stromal TumorsPhase 2NCT06208748
SARC044: A Phase II Trial of Bezuclastinib in Combination With Sunitinib in Patients With GIST
A Phase 2 study testing Bezuclastinib in combination with sunitinib in people with Gastrointestinal Stromal Tumors and GIST, run by Sarcoma Alliance for Research through Collaboration at 4 sites in United States.
Trial summary
This is an open label, single arm, phase 2 trial investigating bezuclastinib plus sunitinib in patients with GIST who have previously progressed on sunitinib. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Stromal Tumors, GIST
- What is being tested?
- Bezuclastinib in combination with sunitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 4 sitesUnited States
- Study dates
- 1 Aug 2024to Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age minimum of 18 years
- Histologically confirmed, inoperable or metastatic GIST with an exon 11 or exon 9 primary KIT mutation. Other primary KIT mutations (e.g., exon 13, exon 17) will be considered on a case-by-case basis after discussion with the Principal Investigator. Pathology reports including mutational analysis should be available for review by the Sponsor.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 (See Appendix A).
- Prior progression on or intolerance to imatinib. Imatinib intolerance is defined as discontinuation of imatinib due to an adverse event(s) related to treatment with imatinib that was not manageable with dose modifications.
- Documented disease progression on sunitinib of at least 25 mg daily as continuous treatment, or 37.5 mg daily with the 4 weeks on/2 weeks of schedule.
- At least one site of measurable disease on CT/MRI scan as defined by modified RECIST version 1.1 (mRECIST v1.1) criteria.
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- Resolution of toxicities from prior therapy to ≤Grade 1 (or baseline), including clinically significant laboratory abnormalities, prior to the first dose of the study drug.
- Adequate organ function:
- Absolute Neutrophil Count (ANC) ≥ 1 x 109/L (unsupported for 7 days, or 14 days if pegfilgrastim was administered)
- Platelets ≥ 100 x 109/L (unsupported for 14 days)
- Hemoglobin ≥8 g/dL (unsupported for 14 days)
- ALT and AST ≤ 2.5 x institutional upper limit of normal (ULN) or ≤ 5.0 x institutional ULN in the presence of hepatic metastases.
- Serum bilirubin ≤ 1.5 x institutional ULN. NOTE: Patients with elevated bilirubin secondary to Gilbert's disease are eligible to participate in the study provided that direct bilirubin ≤1.5 x institutional ULN and indirect bilirubin ≤3 x institutional ULN
- Estimated glomerular filtration rate ≥45 mL/min/1.73 m2
- Ability and willingness to provide written, voluntary informed consent
- Ability to swallow pills
- For male subjects, unless having undergone permanent sterilization (includes bilateral orchidectomy), agreement to use effective barrier contraception (i.e., condoms) during the study treatment period and for 6 weeks after the last dose of study drug.
- For women of childbearing potential (WOCBP), confirmation of negative serum or urine pregnancy test prior to dosing with the study drug and agreement to the use of highly effective method of contraception with or without a barrier contraception method during the study treatment period and for 6 weeks after the last dose of the study drug. Female subjects who are using hormonal contraception must agree to remain on a stable regimen throughout the study unless a change is deemed medically necessary by the Investigator.
- WOCBP are defined as defined as physiologically and anatomically capable of becoming pregnant, unless they meet one of the following conditions:
- Postmenopausal: 12 months of natural (spontaneous) amenorrhea without an alternative medical cause
- Prior hysterectomy
- Prior bilateral oophorectomy
- Prior bilateral salpingectomy
- Highly effective methods of birth control includes:
- Combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation, delivered orally, intravaginally, or transdermally
- Progestogen-only hormonal contraception associated with inhibition of ovulation, delivered orally, via injection, or implanted
- An intrauterine device (IUD)
- An intrauterine hormone-releasing system (IUS)
- Bilateral tubal occlusion
- Vasectomized partner - provided the partner is the sole sexual partner of the WOCBP study participant and that the vasectomized partner has received medical assessment of the surgical success
- Sexual abstinence, when consistent with the preferred and usual lifestyle of the subject, can be considered acceptable based on the evaluation of the Investigator, who should take into consideration the duration of the clinical study. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation) and withdrawal are not considered acceptable methods of contraception.
- Life expectancy of > 12 weeks
- For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
- Patients with central nervous system disease are eligible for enrollment if they have received prior radiotherapy or surgery to sites of CNS metastatic disease and are without evidence of clinical or radiographic progression at the time of enrollment.
Who cannot join
- Prior exposure to bezuclastinib.
- Prior anticancer drug less than 5 half-lives of the parent drug and/or its active metabolite(s) or 14 days (whichever is shorter) prior to the first dose of the study drug.
- Received strong CYP3A4 inhibitor(s) or inducer(s) within 14 days or 5 drug half-lives before the first dose of the study drug, whichever is longer, or the need to continue treatment with strong CYP3A4 inhibitor(s) or inducer(s) during the study.
- GIST without primary activating mutations in KIT exons 11 or 9. Other primary KIT activating mutations will be considered on a case-by-case basis. Patients with GIST with other mutations (e.g., PDGFRA, SDHx, BRAF, or NF1) or unknown genotype are excluded.
- Known or suspected hypersensitivity to bezuclastinib or sunitinib and their components.
- Unacceptable toxicity with prior sunitinib at 25 mg daily.
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- Clinically significant cardiac disease, defined by any of the following:
- Clinically significant cardiac arrhythmias and/or the need for antiarrhythmic therapy (excluding beta blockers or digoxin). Subjects with controlled atrial fibrillation are not excluded.
- Congenital long QT syndrome or use of concomitant medications known to prolong the QT interval as defined in Appendix D.
- A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >470 milliseconds [ms] using Fridericia's QT correction formula).
- Clinically significant history of cardiac disease or congestive heart failure >New York Heart Association Class II. Subjects must not have unstable angina (anginal symptoms at rest) or new-onset angina within 3 months or myocardial infarction within 6 months prior to enrollment.
- Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the 6 months before study drug initiation (except for adequately treated catheter-related venous thrombosis occurring more than 1 month before the first dose of study drug).
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen may be included after discussion with the Principal Investigator.
- Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol.
- Patients known to be seropositive for human immunodeficiency virus (HIV) 1 or 2. HIV testing is not required as part of screening.
- Major surgery (including abdominal laparotomy) within 4 weeks prior to the first dose of study drug, or subjects who have not recovered adequately from prior surgery.
- Gastrointestinal abnormalities including, but not limited to, significant nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption
- Any active bleeding, excluding hemorrhoidal or gum bleeding
- Women who are pregnant or nursing/breastfeeding.
- Patients with untreated central nervous system metastatic disease.
- Inability to comply with protocol required procedures
- Active, uncontrolled, systemic bacterial, fungal, or viral infections at Screening. NOTE: Oral antibiotics for a controlled infection (e.g., urinary tract infection) are permitted provided that the symptoms are mild and expected to resolve with appropriate treatment at the discretion of the investigator. Subjects on antimicrobial, antifungal, or antiviral prophylaxis are not specifically excluded if all other inclusion/exclusion criteria are met.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Sylvester Comprehensive Cancer Center, University of Miami
Miami, Florida, 33136
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Oregon Health & Science University
Portland, Oregon, 97239
About this study
Official title: A Phase II Trial of Bezuclastinib in Combination With Sunitinib in Patients With GIST Who Progressed on Sunitinib Monotherapy
This is an open label, single arm, phase 2 trial investigating bezuclastinib plus sunitinib in patients with GIST who have previously progressed on sunitinib.
Read the detailed description
This is an open label, single arm, phase 2 trial investigating bezuclastinib plus sunitinib in patients with GIST who have previously progressed on sunitinib. After washout, patients will begin bezuclastinib and add sunitinib 2 weeks later. Patients will continue on treatment until progression, unacceptable toxicity, or withdrawal of consent. Patients may stay on treatment beyond progression if there is clinical benefit in the opinion of the investigator. Imaging response assessments will be performed every 8 weeks until the participant reaches 15 months on study. After 15 months, response assessments may be performed every 3 months. Circulating tumor DNA (ctDNA) will be collected at baseline, with sequential initiation of bezuclastinib and sunitinib, at the first response assessment, and at the time of progression. In a subset of 20 patients, PET/CT will be performed at baseline and with sequential initiation of bezuclastinib and sunitinib, and tumor biopsies will be performed on cycle 2 day 1 for correlative studies. EORTC QLQ-C30 will be administered during the study to assess patient-reported quality of life.
- Conditions
- Gastrointestinal Stromal Tumors, GIST
- Being tested
- Bezuclastinib in combination with sunitinib
- Keywords
- GIST, Gastrointestinal Stromal Tumors, Sarcoma, Sunitinib, Bezuclastinib, exon 11 or exon 9 primary KIT mutation
- Medical subject headings
- Gastrointestinal Stromal Tumors, Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bezuclastinib in combination with sunitinibDrug
Bezuclastinib in combination with sunitinib (sutent)
| Study group | Role | What they receive |
|---|---|---|
| bezuclastinib in combination with sunitinib | Experimental | Bezuclastinib 600 mg (tablet) administered orally daily Sunitinib 37.5 mg administered orally daily
Patients will begin bezuclastinib and add sunitinib 2 weeks later. Each cycle is 28 days. Receives: Drug: Bezuclastinib in combination with sunitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
To estimate the median progression free survival (mPFS)
mPFS will be summarized with a Kaplan-Meier curve
Measured: From the time of first dose to the occurrence of disease progression (as accessed by mRECIST v1.1) or death due to any cause prior to documented disease progression, up to 2 years..
Secondary outcomes (6)
To determine KIT mutations in tumor tissue and circulating tumor DNA (ctDNA) associated with primary and acquired resistance to combination bezuclastinib and sunitinib.
Measured: 1 year
To determine the objective response rate (ORR; complete responses + partial responses) at 16 weeks and total ORR in patients treated with bezuclastinib in combination with sunitinib.
Measured: 16 weeks
To determine the clinical benefit rate (complete responses + partial responses + stable disease) at 16 weeks in patients treated with bezuclastinib in combination with sunitinib.
Measured: 16 weeks
To estimate the overall survival, including the overall survival rates at year one and year two.
Measured: 1 year, 2 year
To describe the adverse event profile of bezuclastinib in combination with sunitinib.
Measured: 1 year
To describe patient-reported quality of life outcome measures.
Quality of life will be evaluated using the EORTC-QLQ-C30 with descriptive statistics reported at each timepoint. Changes in quality-of-life measures based on the EORTC-QLQ-C30 will be determined (difference at follow-up and baseline will be summarized). Changes in on-treatment scores compared to baseline will be analyzed to determine patients' perception of their functional status, symptoms, and overall health.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2024
- Study start1 Aug 2024
- Primary completionJun 2026 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastrointestinal Stromal TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sarcoma Alliance for Research through Collaboration
- Sponsor type
- University, hospital or other
- Collaborators
- Cogent Biosciences, Inc., Dana-Farber Cancer Institute, The Life Raft Group
- Responsible party
- Sponsor
- Investigators
- Candace Haddox, MD, Principal investigator, Dana-Farber Cancer InstituteAndrew Wagner, MD, PhD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06208748
- Sponsor's protocol ID
- SARC044
- Status last verified
- Oct 2025
- First submitted
- 20 Dec 2023
- Last updated
- 31 Oct 2025
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Bezuclastinib in Combination With Sunitinib in Patients With GIST Who Progressed on Sunitinib Monotherapy
- ClinicalTrials.gov ID
- NCT06208748
- Acronym / sponsor ID
- SARC044
- Conditions
- Gastrointestinal Stromal Tumors, GIST
- Keywords
- GIST, Gastrointestinal Stromal Tumors, Sarcoma, Sunitinib, Bezuclastinib, exon 11 or exon 9 primary KIT mutation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Sarcoma Alliance for Research through CollaborationUniversity, hospital or other
- Collaborators
- Cogent Biosciences, Inc., Dana-Farber Cancer Institute, The Life Raft Group
- Study start
- 1 Aug 2024 (actual)
- Primary completion
- Jun 2026 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 17 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open label, single arm, phase 2 trial investigating bezuclastinib plus sunitinib in patients with GIST who have previously progressed on sunitinib.
Detailed description
This is an open label, single arm, phase 2 trial investigating bezuclastinib plus sunitinib in patients with GIST who have previously progressed on sunitinib. After washout, patients will begin bezuclastinib and add sunitinib 2 weeks later. Patients will continue on treatment until progression, unacceptable toxicity, or withdrawal of consent. Patients may stay on treatment beyond progression if there is clinical benefit in the opinion of the investigator. Imaging response assessments will be performed every 8 weeks until the participant reaches 15 months on study. After 15 months, response assessments may be performed every 3 months. Circulating tumor DNA (ctDNA) will be collected at baseline, with sequential initiation of bezuclastinib and sunitinib, at the first response assessment, and at the time of progression. In a subset of 20 patients, PET/CT will be performed at baseline and with sequential initiation of bezuclastinib and sunitinib, and tumor biopsies will be performed on cycle 2 day 1 for correlative studies. EORTC QLQ-C30 will be administered during the study to assess patient-reported quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| bezuclastinib in combination with sunitinib | Experimental | Drug: Bezuclastinib in combination with sunitinibBezuclastinib 600 mg (tablet) administered orally daily Sunitinib 37.5 mg administered orally daily Patients will begin bezuclastinib and add sunitinib 2 weeks later. Each cycle is 28 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (35 listed)
- Age minimum of 18 years
- Histologically confirmed, inoperable or metastatic GIST with an exon 11 or exon 9 primary KIT mutation. Other primary KIT mutations (e.g., exon 13, exon 17) will be considered on a case-by-case basis after discussion with the Principal Investigator. Pathology reports including mutational analysis should be available for review by the Sponsor.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 (See Appendix A).
- Prior progression on or intolerance to imatinib. Imatinib intolerance is defined as discontinuation of imatinib due to an adverse event(s) related to treatment with imatinib that was not manageable with dose modifications.
- Documented disease progression on sunitinib of at least 25 mg daily as continuous treatment, or 37.5 mg daily with the 4 weeks on/2 weeks of schedule.
Key exclusion criteria (22 listed)
- Prior exposure to bezuclastinib.
- Prior anticancer drug less than 5 half-lives of the parent drug and/or its active metabolite(s) or 14 days (whichever is shorter) prior to the first dose of the study drug.
- Received strong CYP3A4 inhibitor(s) or inducer(s) within 14 days or 5 drug half-lives before the first dose of the study drug, whichever is longer, or the need to continue treatment with strong CYP3A4 inhibitor(s) or inducer(s) during the study.
- GIST without primary activating mutations in KIT exons 11 or 9. Other primary KIT activating mutations will be considered on a case-by-case basis. Patients with GIST with other mutations (e.g., PDGFRA, SDHx, BRAF, or NF1) or unknown genotype are excluded.
- Known or suspected hypersensitivity to bezuclastinib or sunitinib and their components.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bezuclastinib in combination with sunitinibBezuclastinib in combination with sunitinib (sutent) | Drug | bezuclastinib in combination with sunitinib |
Primary outcome
To estimate the median progression free survival (mPFS)
Time frame: From the time of first dose to the occurrence of disease progression (as accessed by mRECIST v1.1) or death due to any cause prior to documented disease progression, up to 2 years..
mPFS will be summarized with a Kaplan-Meier curve
6 secondary outcomes
To determine KIT mutations in tumor tissue and circulating tumor DNA (ctDNA) associated with primary and acquired resistance to combination bezuclastinib and sunitinib.
Time frame: 1 year
To determine the objective response rate (ORR; complete responses + partial responses) at 16 weeks and total ORR in patients treated with bezuclastinib in combination with sunitinib.
Time frame: 16 weeks
To determine the clinical benefit rate (complete responses + partial responses + stable disease) at 16 weeks in patients treated with bezuclastinib in combination with sunitinib.
Time frame: 16 weeks
To estimate the overall survival, including the overall survival rates at year one and year two.
Time frame: 1 year, 2 year
To describe the adverse event profile of bezuclastinib in combination with sunitinib.
Time frame: 1 year
To describe patient-reported quality of life outcome measures.
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Candace Haddox, MD principal investigator
Dana-Farber Cancer Institute
Andrew Wagner, MD, PhD principal investigator
Dana-Farber Cancer Institute
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bezuclastinib in combination with sunitinib in people with Gastrointestinal Stromal Tumors and GIST, run by Sarcoma Alliance for Research through Collaboration at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 35 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 31 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To estimate the median progression free survival (mPFS) (time frame: From the time of first dose to the occurrence of disease progression (as accessed by mRECIST v1.1) or death due to any cause prior to documented disease progression, up to 2 years..). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2025.