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

NCT ID: NCT05440357

Last Updated: 2025-02-26

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-07-01
• Study Completion Date: 2025-09-30

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.

Conditions

Gastrointestinal Stromal Tumors

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Guangdong Provincial People's Hospital

OTHER

Sponsor Role: collaborator

Nanfang Hospital, Southern Medical University

OTHER

Sponsor Role: collaborator

Sixth Affiliated Hospital, Sun Yat-sen University

OTHER

Sponsor Role: collaborator

Peking University Shenzhen Hospital

OTHER

Sponsor Role: collaborator

Cancer Hospital of Guangxi Medical University

OTHER

Sponsor Role: collaborator

Hainan Cancer Hospital

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Nanchang University

OTHER

Sponsor Role: collaborator

Second Affiliated Hospital of Nanchang University

OTHER

Sponsor Role: collaborator

Yunnan Cancer Hospital

OTHER

Sponsor Role: collaborator

Chongqing University Cancer Hospital

OTHER

Sponsor Role: collaborator

Xinhua Zhang, MD

OTHER

Sponsor Role: lead

Responsible Party

Xinhua Zhang, MD

First Affiliated Hospital, Sun Yat-Sen University

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

zhang xinhua, PhD

Role: PRINCIPAL_INVESTIGATOR

First affiliated hosptial,Sun Yat-sen university

Locations

Chongqing University Cancer Hospital

Chongqing, Chongqing Municipality, China

Site Status: RECRUITING

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, China

Site Status: RECRUITING

Sixth Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Site Status: RECRUITING

The first affiliated hospital,Sun yat-sen university

Guangzhou, Guangdong, China

Site Status: RECRUITING

Peking University Shenzhen Hospital

Shenzhen, Guangdong, China

Site Status: RECRUITING

Hainan Cancer Hospital

Haikou, Hannan, China

Site Status: RECRUITING

Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Site Status: RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Site Status: RECRUITING

Countries

China

Central Contacts

zhang xinhua, PhD

Role: CONTACT

zhangxinhua@mail.sysu.edu.cn

+8620-87332200

Facility Contacts

miao Liu

Role: primary

+8613350319013

Tao CHEN, PhD

Role: primary

+8618520131033

Haiming Wang

Role: primary

+8615989192854

Chen Tao, PhD

Role: primary

Zuofei Li

Role: primary

+8613688802418

Yan Meng

Role: primary

+8618976899886

JiaQing Cao

Role: primary

+8613907008850

Yun Li

Role: primary

+8613317977082

References

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.

Reference Type: BACKGROUND

PMID: 17046465 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22646775 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32511981 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29710216 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29682621 (View on PubMed)

Other Identifiers

No.[2021]784

Identifier Type: -

Identifier Source: org_study_id