Clinical trial NCT06628739: Correlation Between Imatinib Trough Concentration and Efficacy in Advanced GIST Patients with Different Genotypes
Official title: Correlation Between Imatinib Trough Concentration and Efficacy in Advanced Gastrointestinal Stromal Tumors Patients with Different Genotypes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Gastrointestinal Stromal Tumor, Malignant
Lead sponsor: First Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2024-10-08
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression free survival
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: objective response rate
timeFrame: through study completion, an average of 1 year
measure: Overall survival
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: First Affiliated Hospital, Sun Yat-Sen University
name: Zhang Xinhua, Professor
role: STUDY_DIRECTOR
References: