Evaluation of Adjuvant Imatinib Mesilate Efficacy in Intermediate-Risk Gastrointestinal Stromal Tumor with High Genomic Grade Index

The primary objective of this study is to assess the **efficacy** of adjuvant **Imatinib** on the rate of metastatic relapse at 2 years in patients with intermediate-risk **gastrointestinal stromal tumor** (GIST) presenting a high Genomic Grade Index. This is clinically relevant as it aims to determine the potential of Imatinib to reduce the risk of metastasis in a specific subset of GIST patients, which could inform treatment strategies and improve patient outcomes.

Secondary objectives include:

• Comparing the two therapeutic approaches in terms of metastasis-free survival at 1 year, 2 years, and 3 years.
• Comparing the two therapeutic approaches in terms of overall survival.
• Evaluating the clinical and biological tolerance and safety of the two therapeutic approaches.
• Assessing the quality of life of patients under the two therapeutic approaches.

The clinical trial focuses on patients diagnosed with **gastrointestinal stromal tumor** (GIST) who are at intermediate risk and present a high Genomic Grade Index. The study population includes both male and female participants aged 18 years and older, with a Performance Status ranging from 0 to 2. Participants must not have undergone prior radiation therapy, chemotherapy, or molecular targeted or biological therapy in the past three years. Eligible subjects are those who have had surgery for the primary tumor between two weeks and three months before starting adjuvant Imatinib mesylate, with no evidence of residual macroscopic disease post-surgery, although microscopically infiltrated margins are permissible. The trial excludes individuals with distant metastases. The sponsor has not provided information regarding the total number of participants. The trial does not involve a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted in the selection criteria.

The clinical trial is designed to assess the efficacy of **adjuvant Imatinib** in patients with intermediate-risk **gastrointestinal stromal tumor** (GIST) who present a high-risk Genomic Grade Index. This is a multicenter, prospective, randomized, double-blind, controlled study. The trial aims to evaluate the rate of metastatic relapse at two years as the primary endpoint, with secondary endpoints including metastasis-free survival at one, two, and three years, overall survival, clinical and biological tolerance, and patients' quality of life. The trial is expected to conclude by May 2, 2026, with recruitment having started on September 13, 2016.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, performance status, and absence of prior therapies. Following the screening, participants will be randomized and commence treatment with **Imatinib mesilate**, administered orally at a maximum daily dose of 400 mg. The treatment period is set for a maximum of 36 months. Follow-up visits will be scheduled to monitor the participants' health status, adherence to the treatment regimen, and to perform necessary imaging studies, such as thoraco-abdominal and pelvic CT scans, to assess the presence of metastases.

The end-of-study visit will occur at the conclusion of the treatment period or upon early termination. Conditions that may lead to early termination include the occurrence of unacceptable adverse events, disease progression, or withdrawal of consent by the participant. The expected length of participant involvement is up to 36 months, contingent upon individual response and tolerance to the treatment. The trial is conducted under strict adherence to ethical guidelines and regulatory requirements to ensure the safety and well-being of all participants.

The clinical trial involves the use of **Imatinib Mesilate** as the experimental medication. **Imatinib Mesilate** is a chemical substance classified as a protein-tyrosine kinase inhibitor. The pharmaceutical form of the medication is denoted by the code PHF00082MIG. The medication is administered orally, with a maximum daily dose of 400 mg. The total maximum dose is also 400 mg, and the treatment period is capped at 36 months. The medication is not formulated for pediatric use. The primary objective of the trial is to assess the efficacy of adjuvant **Imatinib** in reducing the rate of metastatic relapse at 2 years in patients with intermediate-risk gastrointestinal stromal tumor presenting a high Genomic Grade Index.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of **Imatinib Mesilate**. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial is conducted under authorized conditions, with the status of the trial being "Authorised" as per the latest update.

The efficacy of adjuvant **Imatinib** in patients with intermediate-risk gastrointestinal stromal tumor will be assessed primarily by evaluating the rate of metastatic relapse at 2 years. This primary endpoint will be measured using thoraco-abdominal and pelvic CT scans. Secondary endpoints include 1-year, 2-year, and 3-year metastasis-free survival, overall survival, clinical and biological tolerance, and patients' quality of life. Metastasis-free survival is defined as the time from the baseline visit to the earliest date of documented radiological occurrence of metastasis. Quality of life will be assessed using the French version of the SF36 and the EORTC QLQ-C30 questionnaires.