Clinical trial NCT05440357: Second-line Pharmacotherapy Patterns and Outcomes of Advanced Gastrointestinal Stromal Tumor: A Real-world Study
Official title: Second-line Pharmacotherapy Patterns and Outcomes of Advanced Gastrointestinal Stromal Tumor: A Real-world Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Gastrointestinal Stromal Tumors
Keywords: Gastrointestinal Stromal Tumors
Lead sponsor: First Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
Collaborators: name: Guangdong Provincial People's Hospital
name: Nanfang Hospital, Southern Medical University
name: Sixth Affiliated Hospital, Sun Yat-sen University
name: Peking University Shenzhen Hospital
name: Cancer Hospital of Guangxi Medical University
name: Hainan Cancer Hospital
name: The First Affiliated Hospital of Nanchang University
name: Second Affiliated Hospital of Nanchang University
name: Yunnan Cancer Hospital
name: Chongqing University Cancer Hospital
First posted: 2022-06-30
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Approximately 100 patients with metastatic or unresectable advanced gastrointestinal stromal tumors from tier-3 hospitals who meet the criteria will be enrolled in the study.

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free survival rate
timeFrame: 1 year
Secondary outcomes:
measure: Progression-free survival
timeFrame: 2 years
measure: overall survival (OS)
timeFrame: 2 years
measure: objective response rate (ORR)
timeFrame: 2 years
measure: Time to objective response
timeFrame: 1 year
measure: R0/R1 resection rate
timeFrame: 2 years
measure: EORTC QLQ-C30
timeFrame: Difference between baseline and every 3 month during the follow-up period
measure: Safety-TEAEs
timeFrame: 2 years
Other outcomes:
measure: To explore the association of cilinical outcomes with treatment pattern
timeFrame: 2 years
Locations:
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Sixth Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: The first affiliated hospital,Sun yat-sen university
state: Guangdong
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Haikou
country: China
facility: Hainan Cancer Hospital
state: Hannan
city: Nanchang
country: China
facility: Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
Study officials:
affiliation: First affiliated hosptial,Sun Yat-sen university
name: zhang xinhua, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006 Oct 14;368(9544):1329-38. doi: 10.1016/S0140-6736(06)69446-4.
citation: Li J, Gao J, Hong J, Shen L. Efficacy and safety of sunitinib in Chinese patients with imatinib-resistant or -intolerant gastrointestinal stromal tumors. Future Oncol. 2012 May;8(5):617-24. doi: 10.2217/fon.12.29.
citation: Blay JY, Serrano C, Heinrich MC, Zalcberg J, Bauer S, Gelderblom H, Schoffski P, Jones RL, Attia S, D'Amato G, Chi P, Reichardt P, Meade J, Shi K, Ruiz-Soto R, George S, von Mehren M. Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 Jul;21(7):923-934. doi: 10.1016/S1470-2045(20)30168-6. Epub 2020 Jun 5.
citation: Schuetze SM, Bolejack V, Thomas DG, von Mehren M, Patel S, Samuels B, Choy E, D'Amato G, Staddon AP, Ganjoo KN, Chow WA, Rushing DA, Forscher CA, Priebat DA, Loeb DM, Chugh R, Okuno S, Reinke DK, Baker LH. Association of Dasatinib With Progression-Free Survival Among Patients With Advanced Gastrointestinal Stromal Tumors Resistant to Imatinib. JAMA Oncol. 2018 Jun 1;4(6):814-820. doi: 10.1001/jamaoncol.2018.0601.
citation: Kikuchi H, Hiramatsu Y, Kamiya K, Morita Y, Sakaguchi T, Konno H, Takeuchi H. Surgery for metastatic gastrointestinal stromal tumor: to whom and how to? Transl Gastroenterol Hepatol. 2018 Mar 5;3:14. doi: 10.21037/tgh.2018.02.02. eCollection 2018.