Investigating how gut bacteria affect treatment response in GIST patients

Exploring the Molecular Mechanism of Secondary Resistance to Imatinib in Gastrointestinal Stromal Tumors Based on KIT Mutation

This study is trying to see how the bacteria in the gut affect how well patients with a type of stomach tumor respond to a specific cancer treatment.

Quick facts

• Study type: Observational
• Enrollment: 190 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Xijing Hospital (other)
• Drugs / interventions: Imatinib
• Locations: 1 site (Xi'an, Shaanxi)
• Trial ID: NCT05895942 on ClinicalTrials.gov

What this trial studies

This observational study focuses on Chinese patients with unresectable GIST who have specific C-kit mutations. It aims to explore the relationship between gut microbiota composition and the efficacy of imatinib treatment. By analyzing the gut microbiota, the study seeks to identify potential biomarkers that could predict treatment outcomes and inform personalized treatment strategies. The research will involve standardized treatment with imatinib mesylate while monitoring the patients' gut microbiota and treatment responses.

Who should consider this trial

Good fit: Ideal candidates include Chinese patients with unresectable GIST and C-kit9/11 mutations who have not undergone previous surgery.

Not a fit: Patients with complete gastrointestinal obstruction, perforation, or distant metastasis may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to personalized treatment approaches for GIST patients, improving their response to imatinib.

How similar studies have performed: While the role of gut microbiota in cancer treatment is gaining attention, this specific approach to GIST and imatinib is relatively novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* BMI index 18.5-23.9kg/m2;
* Pathologically diagnosed patients with unresectable GIST, and genetic testing is C-kit9/11 mutation;
* No previous surgery;
* ECOG score: 0-1 points;
* Expected survival period ≥ 6 months;
* All patients should have measurable or evaluable target lesions;
* Able to eat liquid diet The above; no complete gastrointestinal obstruction or perforation; no distant metastasis;
* The main organ functions are normal, that is, the following criteria are met:

  1. The blood routine examination standards must be met (no blood transfusion and blood products within 14 days, no G-CSF use) and other hematopoietic stimulating factors): a) HB≥80 g/L; b) ANC≥1.5×109/L; c) PLT≥100×109/L;
  2. Biochemical tests should meet the following criteria: a) TBIL \<1.5×ULN; b) ALT and AST\<2.0×ULN; c) Serum Cr≤1.5×ULN or endogenous creatinine clearance rate\> 50 mL/min (Cockcroft-Gault formula);
  3. Pulmonary function assessment of normal lung function or mild to moderate abnormality (VC%\>60%, FEV1\>1.2L, FEV1%\>40%, DLco\>40%);
  4. Cardiovascular function evaluation: cardiac function grades I to II;
* Have certain self-care Ability and language comprehension.

Exclusion Criteria:

* 1. Patients with pathological types and primary tumor sites that do not meet the inclusion criteria;
* 2. There is a risk of gastrointestinal perforation;
* 3. Has undergone surgical treatment;
* 4. Have ever suffered from malignant tumor;
* 5. Those with a history of severe lung or heart disease;
* 6. Active infection or unexplained fever \>38.5℃ within 2 weeks before randomization;
* 7. Known major active infection, or the investigator judges that there is a major blood, renal, metabolic, gastrointestinal or endocrine dysfunction;
* 8. Those with a history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
* 9. The subject has active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (positive hepatitis C antibody, and HCV-RNA is higher than the detection limit of the analytical method);
* 10. Those who have been vaccinated with live vaccines within 3 months before treatment;
* 11. During acute or chronic tuberculosis infection (positive T-spot test and suspected tuberculosis foci on chest X-ray);
* 12. Those with a history of drug, drug or alcohol abuse (drinking ≥5 times a week, etc.);
* 13. Intravenous infusion cannot be performed;
* 14. Severe diarrhea in the past 2 months (watery stools ≥ 3 times per day and lasted ≥ 3 days);
* 15. Severe constipation (≤2 times of defecation per week with difficulty in defecation) in the past 2 months;
* 16. Antibiotics have been used in the past 2 months for 3 days or more;
* 17. Have used proton pump gastric drugs, acid suppressants, mucosal protective agents, opioid psychotropic drugs, hormones, immunosuppressants, cytotoxic drugs and other drugs within the past 2 months for 3 days or more;
* 18. Have used probiotics, prebiotics or synbiotic within the past 2 months for 3 days or more;
* 19. Received drug treatment for the following diseases in the past 1 month: cholecystitis, peptic ulcer, urinary tract infection, acute pyelonephritis, cystitis, hyperthyroidism and other abnormal thyroid function;
* 20. Gastrointestinal surgery, appendicitis surgery, enema, colon cleansing and other medical operations within the past 1 year;
* 21. During pregnancy and lactation (women) or lactose intolerance;
* 22. Patients with high blood pressure that cannot be reduced to the normal range after antihypertensive drug treatment (systolic blood pressure\>140 mmHg, diastolic blood pressure\>90 mmHg); patients with a history of unstable angina pectoris; newly diagnosed within 3 months before screening Angina pectoris or myocardial infarction within 6 months before screening; arrhythmia (including QTcF: ≥450 ms for men, ≥470 ms for women) requires long-term use of antiarrhythmic drugs and New York Heart Association classification ≥ grade II cardiac insufficiency;
* 23. According to the judgment of the investigator, the subject has other factors that may cause him to be forced to terminate the study halfway, such as suffering from other serious diseases (including mental illness) requiring combined treatment, serious abnormal laboratory test values, family or social factors, Situations that may affect the safety of subjects or the collection of trial data;
* 24. The investigator judges other circumstances that may affect the conduct of clinical research and the judgment of research results;
* 25. Research center staff, researcher's partner or first-degree relative;

Where this trial is running

Xi'an, Shaanxi

• Xijing Hospital of Air Force Military Medical University — Xi'an, Shaanxi, China (RECRUITING)

Study contacts

• Study coordinator: jun j Yang, Master

Conditions: GIST