Ripretinib Used for Resectable Metastatic GIST After Failure of Imatinib Therapy

• Status: Recruiting
• Trial end date: 2023-11-30
• Target enrollment: 0
• Participant gender: All

Summary

To explore the efficacy and safety of preoperative treatment of potentially resectable locally advanced or recurrent metastatic gastrointestinal stromal tumor (GIST) after failure of treatment.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: RenJi Hospital

Criteria

Inclusion Criteria:

Patients must meet all of the following inclusion criteria to be enrolled in the study:

1. Patients voluntarily, and signed a written informed consent, good compliance with follow-up;

2. 18 years ≤ age < 75 years, male or female;

3. Histopathological examination confirmed the diagnosis of gastrointestinal stromal tumors, and immunohistochemical detection of CD117 and/or DOG-1 positive;

4. According to the modified RECISTv1.1-GIST-specific (hereinafter referred to as"mRECIST") criteria, the subject has at least one measurable lesion (the long diameter of non-lymph node lesions is ≥ 1.0 cm or ≥ 2 times the scanning slice thickness); the lesions with definite progression after local treatment can also be considered as measurable lesions; the imaging results must be obtained within 21 days before the first dose;

5. Potentially resectable locally advanced or recurrent metastatic gastrointestinal stromal tumors who have failed imatinib treatment:

• The number of evaluable lesions is ≤ 5 as judged by CT/MRI;

• The resection is considered to have significant risks by MDT assessment (meeting any of the following):

1. The maximum diameter of a single lesion is ≥ 10 cm;

2. Organ function damage surgery is required (gastrectomy, total gastrectomy, hepatectomy residual liver body ≤ 50% of the normal liver volume);

3. Multiple organ resection surgery is required (partial gastrectomy combined with pancreatectomy/splenectomy, pancreaticoduodenectomy and abdominoperineal resection);

6. The ECOG physical status score of patients is 0-2;

7. Good organ function and bone marrow reserve, including:

• Neutrophil count ≥ 1.5 × 109/L

• Hemoglobin ≥ 90 g/L

• Platelets ≥ 100 × 109/L

• Total bilirubin ≤ 1.5 × upper limit of normal (ULN)

• AST and ALT ≤ 3 × ULN, and ≤ 5 × ULN in the presence of liver metastases

• Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min (calculated according to Cockcroft-Gault formula)

• Prothrombin time (PT), international normalized ratio (INR) and partial thromboplastin time ≤ 1.5 × ULN.

• QTc ≤ 450 ms (male), 470 (female): LVEF ≥ 50%

8. Non-surgically sterilized or female patients of childbearing age need to use a medically recognized contraceptive (such as intrauterine device, contraceptives or condoms) during study treatment and within 90 days after the end of study treatment; non-surgically sterilized female patients of childbearing age need to confirm that they are not pregnant; and must be non-lactating; for male patients with partners of childbearing age, effective regimen contraception should be used during study treatment and within 90 days after the end of study treatment.

Exclusion Criteria:

Patients with any of the following will not be enrolled in the study:

1. Patients with other serious complications who cannot tolerate surgery: such as severe cardiopulmonary disease, heart function below clinical class 2, pulmonary infection, moderate to severe COPD, chronic bronchitis, severe diabetes and/or renal insufficiency, severe hepatitis and/or Child-pugh class C or B whose symptoms are significantly difficult to correct, severe malnutrition, etc.;

2. Occurrence of bleeding, perforation, obstruction and other disease-related complications, requiring emergency surgery;

3. Patients with severe mental illness;

4. The patient has participated in or is participating in other clinical studies , or is taking other TKI agents; has any clinically significant concurrent medical condition such as uncontrolled pulmonary disease, active infection, or any other condition that, in the opinion of the investigator, may affect patient compliance, interfere with interpretation of study results, or expose the patient to safety risks.

5. Active viral infections such as human immunodeficiency virus, hepatitis B, and hepatitis C

6. Pregnant or lactating female patients or patients expecting to become pregnant during study treatment

7. Known hypersensitivity to any component of the study drug.

8. Gastrointestinal abnormalities, including but not limited to:

• Inability to swallow study drug

• Malabsorption syndrome

• Need for intravenous nutrition

9. Any active bleeding, excluding hemorrhoids or gingival bleeding. Has any clinically significant concurrent medical condition, such as uncontrolled pulmonary disease, active infection, or any other condition that, in the opinion of the investigator, may affect patient compliance, interfere with interpretation of study results, or expose the patient to safety risks.

10. The investigator considers that there are other factors that may affect the study results or cause the study to be terminated, such as alcoholism, drug abuse, other serious diseases (including mental illness) requiring concomitant treatment, severe laboratory abnormalities, with family or social factors that may affect the safety of patients.

11. Other patients who may affect the conduct of the clinical study in the judgment of the investigator, may be unable to comply with the agreement or unable to cooperate, patients with study risks.