Clinical trial NCT05867901: Clinical Research of Drug Holiday Based on MRD Detection in GIST Patients at High Risk of Recurrence
Official title: Clinical Research of Drug Holiday Based on MRD Detection in Gastrointestinal Stromal Tumor Patients at High Risk of Recurrence
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Gastrointestinal Stromal Tumors
Keywords: Gastrointestinal Stromal Tumors
Drug Holiday
Minimal Residual Disease
Circulating Tumor DNA
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2023-05-22
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: High-risk GIST patients who have been treated with imatinib for more than 3 years after surgery and have no gross lesions in imaging examination

Brief summary: This study is aimed:

* to evaluate the dynamic monitoring value of MRD detection for postoperative recurrence in high-risk GIST patients;

  * to evaluate the effect of drug holiday mode based on MRD detection on progression-free Survival (PFS) and/or overall survival (OS) after drug withdrawal for high-risk GIST patients who have achieved disease control after long-term use of imatinib; ③ to investigate the response rate of imatinib re-use in patients who developed disease progression after drug withdrawal; ④ to explore whether the "drug holiday" treatment mode based on MRD detection could delay the occurrence of secondary imatinib resistance mutations for high-risk GIST patients with long-term use of imatinib after surgery.

Detailed description: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract, and surgery is the preferred treatment method for primary resectable GIST. The guidelines recommend that patients at high risk of recurrence should be treated with tyrosine kinase inhibitors (TKI) such as imatinib for at least 3 years after surgery. However, in actual clinical practice, some patients face the situation of early withdrawal or prolonged medication, so the timing of drug withdrawal needs to be further studied. Recent studies have reported that some GIST patients who have achieved disease control through long-term use of imatinib can still achieve a long progression-free survival after drug withdrawal, and those who relapse after drug withdrawal can still achieve disease control after re-use of imatinib. This suggests that for some selected patients, a "drug holiday" treatment mode could be possible, in which drugs are discontinued when appropriate and restarted if necessary. How to select patients suitable for this mode of treatment needs further exploration. Liquid biopsy of peripheral blood circulating tumor DNA (ctDNA) to detect minimal residual disease (MRD) can be used for the diagnosis, efficacy evaluation, recurrence and drug resistance monitoring of a variety of malignant tumors. Existing studies have explored the "drug holiday" treatment mode based on MRD detection assisting patients with advanced non-small cell lung cancer to use TKI. Therefore, this one-arm prospective observational clinical study will assist some high-risk GIST patients who have been treated with imatinib for 3 years after surgery and have achieved disease control to adopt the treatment mode of "drug holiday" based MRD detection, aiming to evaluate the value of MRD detection in monitoring postoperative recurrence of high-risk GIST, investigate the effect of "drug holiday" treatment mode based on MRD detection on disease recurrence and patient survival, and to explore whether it can delay the occurrence of drug-resistant mutations.

Eligibility criteria: Inclusion Criteria:

* ① Age: ≥18 years and ≤75 years;
* ② The primary lesion (and metastatic lesion) underwent R0 or R1 surgical resection, and patients were clinically diagnosed with high recurrence risk GIST combined with postoperative pathological results;
* ③ The patient have received imatinib adjuvant therapy for 3 years after surgery, and no gross lesions were detected by imaging examination, and the possibility of drug withdrawal was considered based on the comprehensive judgment of the doctor in charge;
* ④ The liquid biopsy for baseline ctDNA is negative;
* ⑤ Primary Imatinib resistant mutations were not detected by genetic testing, such as SDH-deficient GIST, NF1-mutant GIST, BRAF-mutant GIST and GIST with NTRK3 rearrangement;
* ⑥ PS score is 0-1 and expected survival time is more than 4 months;
* ⑦ Patients are willing to stop drug use and observe, and patients and their families could understand the study protocol and voluntarily participate in this study, and signed informed consent. In the follow-up study, they could provide the clinical pathological data and imaging data needed for the study process, cooperate with the follow-up and collect the blood of the clinical efficacy evaluation, and agree to use the test data for the follow-up study and product development.

Exclusion Criteria:

* ① Fresh or paraffin tissue of the surgical tumor is not available;
* ② Not receiving the assigned treatment or change therapy before disease progression;
* ③ Unable to cooperate with follow-up with the study according to defined clinical period;
* ④ Unable to take or provide defined imaging assessment examinations;
* ⑤ Other conditions that investigators consider inappropriate for enrollment.

Primary outcomes:
measure: Progress-free Survival
timeFrame: From date when patients first enter the drug holiday until the date of imaging examinations confirmed disease progression up to 3 years
measure: Drug re-use rate
timeFrame: 3 years from the time when patients first enter the drug holiday
measure: Drug retreatment response rate
timeFrame: 3 years from the time when patients first enter the drug holiday
Secondary outcomes:
measure: Overall Survival
timeFrame: From date when patients first enter the drug holiday until the date of death up to 3 years
measure: genetic mutation profiling of ctDNA-MRD
timeFrame: 3 years from the time when patients first enter the drug holiday
measure: MRD versus imaging examination
timeFrame: 3 years from the time when patients first enter the drug holiday
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
Study officials:
affiliation: Peking University People's Hospital
name: Zhidong Gao, MD
role: PRINCIPAL_INVESTIGATOR
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