Advanced (unresectable or metastatic) gastrointestinal stromal tumor (GIST) refractory to at least two prior tyrosine kinase inhibitors (TKIs) including imatinib
Conditions
Interventions
Experimental Arm (TIR Combination):Regorafenib + Sintilimab + Radiotherapy.
Regorafenib: 120 mg orally once daily, 3 weeks on / 1 week off (28-day cycle).
Sintilimab: 200 mg intravenously once every 3
Control Arm (Regorafenib Monotherapy):Regorafenib (Stivarga), same regimen as the experimental group.
Sponsors
Sun Yat-Sen University Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Aged >= 18 years on the day of signing informed consent. 2.Histologically confirmed diagnosis of gastrointestinal stromal tumor (GIST), supported by either immunohistochemistry (positive for CD117 and/or DOG-1) or molecular testing (KIT or PDGFRA mutation). 3.Unresectable locally advanced or metastatic GIST as determined by multidisciplinary team (MDT) evaluation, with at least one measurable lesion per RECIST v1.1. 4.Documented disease progression per RECIST v1.1 or unacceptable toxicity during or after the most recent tyrosine kinase inhibitor (TKI) therapy, following prior treatment with at least two TKIs including imatinib. Prior treatment with additional lines of systemic therapy is permitted, but prior exposure to regorafenib or any PD-1/PD-L1 inhibitor is not allowed. 5.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients with ECOG 2 may be considered after investigator assessment of tolerability to radiotherapy and immunotherapy. 6.Adequate baseline organ and bone marrow function defined as: absolute neutrophil count (ANC) >= 1.5 × 10?/L, platelet count >= 100 × 10?/L, and hemoglobin >= 9 g/dL. 7.Total serum bilirubin = 1.5 × upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 50 mL/min, calculated by the Cockcroft–Gault formula (or by the MDRD formula for patients > 65 years of age). 9.Recovery from toxicity related to prior antineoplastic therapy to CTCAE Grade = 3 months. 15.At least one lesion considered suitable for radiotherapy as assessed by a qualified radiation oncologist.
Exclusion criteria
Exclusion criteria: 1.Prior treatment with regorafenib or any PD-1, PD-L1, or CTLA-4 inhibitor. 2.Receipt of any other antineoplastic therapy (chemotherapy, targeted therapy, immunotherapy, extensive radiotherapy, etc.) within 4 weeks prior to randomization, or persistent toxicity from prior therapy that has not resolved to CTCAE Grade = 4 weeks, off corticosteroids, and radiographically stable. 4.Pregnant or breastfeeding women. 5.History of seizures or current need for antiepileptic medication. 6.Significant comorbidities affecting the cardiovascular, hepatic, renal, or hematopoietic systems, or any other clinically significant condition that, in the investigator's judgment, makes the patient unsuitable for the study or may interfere with study procedures or results. 7.History of any other malignancy within the past 3 years, except adequately treated basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix. 8.Concurrent use of warfarin (or alternative anticoagulants such as low-molecular-weight heparin) or any prohibited concomitant medication. 9.New York Heart Association (NYHA) Class III or IV cardiac disease, including congestive heart failure or myocardial infarction within the previous 6 months. 10.Known infection with human immunodeficiency virus (HIV). 11.Major surgery within 2 weeks prior to enrollment. 12.Psychiatric disorders or other conditions that would prevent the patient from complying with the study requirements. 13.Any history, disease evidence, treatment, or laboratory abnormality that may interfere with study results or prevent full participation, or any other condition deemed by the investigator to pose unacceptable risk for study participation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| progression-free survival (PFS); | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival (OS);Disease Control Rate (DCR);Safety and Tolerability;Objective Response Rate (ORR);Quality of Life (QoL); | — |
Countries
China
Contacts
Public ContactHaibo Qiu
Sun Yat-Sen University Cancer Center
Outcome results
None listed