NCT05385549

5 Years of Adjuvant Imatinib in Patients With Gastrointestinal Stromal Tumor With a High Risk

A Phase 2 Study of 5 Years of Adjuvant Imatinib in Patients With Gastrointestinal Stromal Tumor With a High Risk of Recurrence Following Surgical Resection

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 35 (estimated)
• Sponsor: Asan Medical Center · Academic / Other
• Sex: All
• Age: 20 Years
• Healthy volunteers: Not accepted

Summary

In this study, the investigators aim to investigate the efficacy and safety of 5 years of adjuvant imatinib treatment in patients with tumor rupture defined by Nishida classification or those with a tumor size 10cm or larger and a mitotic index of 10/50HPFs or higher.

Detailed description

Localized resectable GISTs can be cured with surgical resection, but no effective therapy had been established for patients with unresectable and/or metastatic GISTs and their prognosis was extremely poor before the advent of imatinib. Imatinib mesylate is an oral tyrosine-kinase inhibitor (TKI) with activity against KIT, PDGFRA, ABL, and DDR. The efficacy of imatinib was first shown in the pivotal B2222 trial and confirmed by two subsequent randomized phase III trials. The standard dose of imatinib was established as a 400mg once daily dose upfront high-dose imatinib treatment with a 800mg daily dose showed a higher efficacy in terms of progression-free survival (PFS) in patients with GISTs harboring KIT exon 9 mutations but also higher toxicity. The median time-to-progression (TTP) with imatinib was about 2 years in the extended follow-up results of the B2222 trial. Imatinib efficacy correlates with primary KIT mutations and patients with KIT exon 9 mutations had worse survival outcomes than those with KIT exon 11 mutations. Surgical resection is the mainstay of the treatment of localized GIST. However, in a proportion of patients, a high recurrence rate was observed, which prompted the investigation of the clinical efficacy of adjuvant imatinib treatment. The ACOSSOG Z9001 study showed that one year of adjuvant imatinib treatment after surgical resection in patients with a tumor size of 3cm of larger improved recurrence-free survival compared to placebo. This study was the first to demonstrate the efficacy of adjuvant imatinib treatment. Subsequently, SSG XVIII/AIO study showed that 3 years of adjuvant imatinib improved recurrence-free survival and overall survival compared to one year of adjuvant imatinib in High risk patients defined by modified NIH criteria. Based on this study in patients classified as high risk by the modified NIH criteria, 3 years adjuvant imatinib is the standard of care. However, given that a substantial proportion of such patients show disease recurrence, the PERSIST5 study recently showed that 5 years of imatinib treatment may further reduce the recurrence. In addition, clinical outcomes of the patients classified as high risk by the modified NIH criteria are heterogeneous, and some of these patients show particularly poor clinical outcomes. The investigators analyzed the clinical outcomes of 222 high risk GIST patients who received 3 years of adjuvant imatinib treatment following surgical resection. Among these, patients with tumor rupture defined by Nishida classification or those with a tumor size 10cm or larger and a mitotic index of 10/50HPFs or higher had poor clinical outcomes with a 5-year recurrence-free survival of 50%. In this study, the investigators aim to investigate the efficacy and safety of 5 years of adjuvant imatinib treatment in patients with tumor rupture defined by Nishida classification or those with a tumor size 10cm or larger and a mitotic index of 10/50HPFs or higher.

Conditions

• Gastrointestinal Stromal Tumors

Interventions

Type	Name	Description
DRUG	Imatinib Mesylate	Imatinib Mesylate, 400 mg once daily, oral. 5 years of adjuvant imatinib treatment (standard treatment 3years + IP treatment : 2yesrs)

Timeline

• Start date: 2022-09-07
• Primary completion: 2030-04-30
• Completion: 2030-04-30
• First posted: 2022-05-23
• Last updated: 2025-08-08

Locations

1 site across 1 country: South Korea