Trial Title:
SARC044: A Phase II Trial of Bezuclastinib in Combination With Sunitinib in Patients With GIST
NCT ID:
NCT06208748
Condition:
Gastrointestinal Stromal Tumors
GIST
Conditions: Official terms:
Gastrointestinal Stromal Tumors
Sunitinib
Conditions: Keywords:
GIST
Gastrointestinal Stromal Tumors
Sarcoma
Sunitinib
Bezuclastinib
exon 11 or exon 9 primary KIT mutation
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Bezuclastinib in combination with sunitinib
Description:
Bezuclastinib in combination with sunitinib (sutent)
Arm group label:
bezuclastinib in combination with sunitinib
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.
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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.
- 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Sylvester Comprehensive Cancer Center, University of Miami
Address:
City:
Miami
Zip:
33136
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
Dana Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Facility:
Name:
Oregon Health & Science University
Address:
City:
Portland
Zip:
97239
Country:
United States
Status:
Recruiting
Facility:
Name:
Fox Chase Cancer Center
Address:
City:
Philadelphia
Zip:
19111
Country:
United States
Status:
Recruiting
Start date:
July 2024
Completion date:
June 2027
Lead sponsor:
Agency:
Sarcoma Alliance for Research through Collaboration
Agency class:
Other
Collaborator:
Agency:
Cogent Biosciences, Inc.
Agency class:
Industry
Collaborator:
Agency:
Dana-Farber Cancer Institute
Agency class:
Other
Collaborator:
Agency:
The Life Raft Group
Agency class:
Other
Source:
Sarcoma Alliance for Research through Collaboration
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06208748
