Correlation Between Imatinib Trough Concentration and Efficacy in Advanced GIST Patients with Different Genotypes

Correlation Between Imatinib Trough Concentration and Efficacy in Advanced Gastrointestinal Stromal Tumors Patients with Different Genotypes

Imatinib (IM) has significantly enhanced the prognosis of patients (pts) with advanced gastrointestinal stromal tumors (GISTs). The clinical outcomes may correlate with IM exposure. However, the efficacy threshold, particularly based on different primary KIT mutant, remains undefined. The objective of this study is to establish the efficacy threshold of imatinib (IM) plasma trough concentration (Cmin) at steady-state in Chinese patients with advanced GIST, additionally to define subgroup thresholds based on various primary KIT mutations.

Study Overview

• Status: Completed
• Conditions: Gastrointestinal Stromal Tumor, Malignant
• Intervention / Treatment: Drug: Imatinib

Detailed Description

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. The majority of GIST are driven by activating mutuations of KIT (60-70%) or platelet-derived growth factor receptor alpha (PDGFRA, 10-15%), in which KIT exon 11 mutation (52-58%) and KIT exon 9 mutation (6-9%) are the most common types of KIT mutations. Patients with different activating KIT mutations have different sensitivity to imatinib therapy. In the first-line therapy, patients with KIT exon 11 mutation receiving Imatinib with standard dose of 400mg/d has the best therapeutic effect. Patients with KIT exon 9 mutation have poor sensitivity to the standard dose of imatinib, while higher doses can lead to better outcomes. The clinical outcomes may correlate with IM exposure. However, the efficacy threshold of imatinib in Chinese patients with advanced GIST remains unclear. The investigators aim to establish the efficacy threshold of imatinib plasma trough concentration (Cmin) at steady-state in Chinese patients with advanced GIST, additionally to define subgroup thresholds based on various primary KIT mutations.

• Study Type: Observational
• Enrollment (Actual): 168

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital of Sun Yat-Sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

From July 2017 to June 2022, 168 patients with advanced GIST who received imatinib treatment regularly and had pharmacokinetic (PK) blood samples availabe were enrolled in the study.

Description

Inclusion Criteria:

• Histologically confirmed metastatic or recurrent GIST
• Aged 18 or older
• Treated with imatinib as first-line therapy
• Had imatinib Cmin measurement at steady state(at least one month after treatment) ≥2 times under long-term maintenance dose of regular medication
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2

Exclusion Criteria:

• Poor appliance
• Important treatment data missing
• Combined use of CYP enzyme inducers or inhibitors, such as rifampicin, carbamazepine, ketoconazole, ritonavir, rifamequal

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
IM Cmin below deciles boundary; Patients with imatinib Cmin less than the decile boundary based on each imatinib Cmin distribution decile.
IM Cmin above deciles boundary; Patients with imatinib Cmin greater than or equal to the decile boundary based on each imatinib Cmin distribution decile.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Progression free survival (PFS) was defined as time from initiation of imatinib treatment until disease progression, as assessed by Choi criteria, or death caused by any reason.	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate	Objective response rate (ORR) was defined as rate of Complete Response (CR) and Partial Response (PR).	through study completion, an average of 1 year
Overall survival	Overall survival (OS) was defined as time from initiation of imatinib treatment until death caused by any reason.	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: First Affiliated Hospital, Sun Yat-Sen University
• Investigators: Study Director: Zhang Xinhua, Professor, First Affiliated Hospital, Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): May 31, 2023

Study Registration Dates

• First Submitted: May 27, 2024
• First Submitted That Met QC Criteria: October 4, 2024
• First Posted (Actual): October 8, 2024

Study Record Updates

• Last Update Posted (Actual): October 8, 2024
• Last Update Submitted That Met QC Criteria: October 4, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: No.[2023]184

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No