Second-line Pharmacotherapy Patterns and Outcomes of Advanced Gastrointestinal Stromal Tumor: A Real-world Study

Study Overview
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Brief Summary
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This is a prospective, multicenter, observational real-world study to explore the second-line Pharmacotherapy patterns and clinical outcomes in GIST patients who progressed on or were intolerant to first-line anticancer treatment.

Detailed Description
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INTRODUCTION AND RATIONALE Gastrointestinal stromal tumors (GIST) are thought to develop from the interstitial cells of Cajal or their stem cell precursors. They are the most common mesenchymal tumors occurring in the gastrointestinal (GI) tract. The annual incidence of GIST is about 1/100,000   2/100,000 globally. Previous data showed that the incidence of GIST was 0.43 per 100,000 in Shanxi Province and 2.11per 100,000 in Shanghai in China. Surgery is the primary therapy for patients with localized resectable disease. GIST that is metastatic or locally advanced but unresectable is treated with tyrosine kinase inhibitors (TKIs) that target KIT or PDGFRA. Imatinib is recommended as the first-line standard treatment for metastatic or unresectable advanced GIST. Most patients with initial clinical benefits from Imatinib eventually progress. However, approximately 10% -14% of GIST is primarily resistant to imatinib and 90% of patients will develop secondary drug resistance within 4 years with imatinib treatment. For patients who failed imatinib first-line treatment, Sunitinib is the standard second-line therapy but not the optimal treatment regimen in clinical practice. Other TKIs targeting KIT is also used in the second-line setting. A phase 3 study to evaluate sunitinib's efficacy in advanced GIST compared with placebo, showed that the mPFS was 5.6 months [2], while a phase I study of ripretinib demonstrated that the mPFS was10.7months as a second-line treatment in advanced GIST[4]. Another single-arm second-line treatment study of dasatinib also suggested that dasatinib had a tumor suppression effect in the treatment of advanced GIST with imatinib treatment failure, with mPFS of 2.9 months, and mOS of 19 months, especially for patients with SRC overexpression and PDGFRA D842V mutation [5]. There is a lack of real-world data on advanced GIST patients who have progressed on first-line treatment with different treatment patterns, and the benefits are also unknown. The investigators initiate this prospective, observational, real-world study that aims to explore the second-line treatment patterns and the clinical outcomes in GIST patients who progressed on or were intolerant to first-line treatment in real-world clinical practice. STUDY PROCEDURE Approximately 100 patients will be enrolled. According to the inclusion criteria, patients will receive second-line treatment that was recommended by the current guidelines, including sunitinib, imatinib dose-escalation, repritinib, dasatinib, and other drugs based on the physician's judgment. Data will be collected based on a real-world setting. SCREENING PERIOD During the screening period, the informed consent form will be signed before enrolling. Radiologic imaging and dermatologic examination should be performed within 30 days before the first day of enrollment. Baseline information, including medical history, previous treatment pattern, ECOG PS score, EORTC-QLQ-C30 scale, molecular detection, and any laboratory test should be recorded. OBSERVATION PERIOD Patients will be enrolled in the study after confirmation of all eligibility criteria. The treatment patterns will be decided by the physician. Study visits during the Treatment Period will occur every 2 months. Regular physical examination, vital signs, imaging examination, tumor assessment(PFS and ORR), EORTC-QLQ-C30, 2. ECOG PS score, the dose of drug and dose Administration, and drug-related adverse events will be recorded during each visit. FELLOW-UP PERIOD Patients will be contacted by phone call for the Safety Follow-up Visit 30 days after the last visit of study. Any AEs, medications, including anticancer treatments, and survival status will be followed during this period.

Official Title
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Second-line Pharmacotherapy Patterns and Outcomes of Advanced Gastrointestinal Stromal Tumor: A Real-world Study

Conditions
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Gastrointestinal Stromal Tumors

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who are aged ≥ 18 years. Patients who have histologically confirmed metastatic or unresectable GIST. Patients who received imatinib at a fixed dose or 1 other TKI as prior treatment regimens. Patients who experienced intolerance to prior therapies must have objective disease progression before enrollment. Patients must have at least a measurable lesion according to mRECIST Version 1.1. According to the current GIST national guidelines, patients who receive second-line treatments, including but not limited to sunitinib, imatinib dose escalation, ripretinib, dasatinib, and other drug treatments. Patients with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2 at screening. Exclusion Criteria: Patients who previously received two or more TKIs as prior treatment regimens. Patients with a life expectancy of fewer than three months. Patients who are pregnant and lactating. Patients with an estimated poor adherence or inability to complete follow-up. Patients who are not appropriate to enroll due to the investigator's consideration.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival rate | The primary objective is to demonstrate the proportion of patients with progression-free survival (PFS) determined by radiological assessment per modified Response Evaluation Criteria in Solid Tumors (mRECIST), version 1.1 in patients with advanced GIST following the second-line treatment. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | To evaluate PFS determined by radiology assessment per mRECIST, version 1.1 in patients with advanced GIST treated with second-line treatment. | 2 years | 
| overall survival (OS) | To evaluate overall survival (OS) in patients with advanced GIST treated with second-line treatment. | 2 years | 
| objective response rate (ORR) | To evaluate objective response rate (ORR) determined by radiology assessment per mRECIST, version 1.1 in patients with advanced GIST treated with second-line treatment. | 2 years | 
| Time to objective response | Time to objective response is defined as the interval between the date of randomization and the earliest documented evidence of the best objective reponse based on the independent radiologic review the best objective response rate (ORR) determined by radiology assessment per mRECIST, version 1.1 in patients with advanced GIST treated with second-line treatment. | 1 year | 
| R0/R1 resection rate | To evaluate the proportion of patients who performed R0/R1 resection surgery with advanced GIST treated with second-line treatment. | 2 years | 
| EORTC QLQ-C30 | QOL as measured by using EORTC QLQ-C30, Change in Individual Scores in Patients With Advanced GIST Treated under second-line treatment | Difference between baseline and every 3 month during the follow-up period | 
| Safety-TEAEs | Treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), serious adverse events (SAEs), dose reduction or discontinuation of study drug due to toxicity; changes from baseline in ECOG PS; Incidence of surgical complications. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastrointestinal Stromal Tumors