Prediction of Postoperative Treatment Efficacy and Recurrence Risk of High-risk GIST Based on Liquid Biopsy MRD

• ClinicalTrials.gov Identifier: NCT05408897
• Recruitment Status: Recruiting
• First Posted: June 7, 2022
• Last Update Posted: September 21, 2022
• Sponsor: Peking University People's Hospital
• Information provided by (Responsible Party): YE Yingjiang, Peking University People's Hospital

Study Description

Brief Summary:

So far, MRD assessment by liquid biopsy (ctDNA) has not been used to predict postoperative treatment efficacy and recurrence risk of GIST patients because of special disease characteristics and technological limitations. Therefore, we conducted this prospective multi-center, single-arm observational study to collect 45 operable patients with locally advanced, suspected high-risk GIST. NGS genetic testing platform is used to detect tumour tissues and peripheral ctDNA will also be dectected. we try to explore the correlation between PFS/OS and MRD in high-risk GIST patients by analyzing the relationship between dynamic changes in ctDNA mutation spectrum and postoperative adjuvant therapy efficacy, and to evaluate MRD-based genomic characteristics to guide further treatment.

Condition or disease	Intervention/treatment
Gastrointestinal Stromal Tumors; Minimal Residual Disease	Diagnostic Test: liquid biopsy

Detailed Description:

Assessing MRD (Minimal Residual Disease) and predicting the postoperative adjuvant treatment efficacy and recurrence risk of tumor patients based on ctDNA (circulating tumor DNA) detected by liquid biopsy have been exploratorily studied and applied in many types of cancers. However, as for GISTs (gastrointestinal stromal tumors), the most common mesenchymal neoplasm of the gastrointestinal tract, they have less peripheral ctDNA fragments compared with those tumors of hematological or epithelial origins. Since there are also some limitations of previous detection technology and detection depth, prospective study for prediction of postoperative treatment efficacy and recurrence risk of high-risk GIST is lacking.

In this study, a prospective multi-center, single-arm observational study is conducted to collect operable patients with locally advanced GIST. According to results of preoperative imaging examinations or pathological biopsy, 45 high-risk GIST patients will be screened and enrolled. Next-Generation Sequencing (NGS) genetic testing platform (Burning Rock Oncoscreen Plus TM) is used to detect the baseline tumour tissues (detection depth 1000X) of these patients. And peripheral ctDNA (detection depth 30000X) of multiple pre/postoperative time points will be detected. The genetic profile and clinical information of each patient will be collected. Combining all the information, bioinformatics analysis will be carried out on the gene detection results of these patients at each time point, and the correlation between the postoperative recurrence time and the ctDNA positive rate/postoperative clearance rate of patients will be compared. The characteristics changes and dynamic changes of tumor release degree will also be analyzed. To explore the correlation between PFS/OS and MRD in high-risk GIST patients, we plan to analyze the relationship between dynamic changes in ctDNA mutation spectrum and postoperative adjuvant therapy efficacy, and to evaluate MRD-based genomic characteristics to guide further treatment.

Study Design

• Study Type: Observational
• Estimated Enrollment: 45 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: Prediction of Postoperative Treatment Efficacy and Recurrence Risk of High-risk GIST Based on Minimal Residual Disease Detected by Liquid Biopsy
• Actual Study Start Date: January 1, 2022
• Estimated Primary Completion Date: April 2023
• Estimated Study Completion Date: April 2028

Groups and Cohorts

Intervention Details:

• Diagnostic Test: liquid biopsy
  A test that enables the diagnosis or analysis of tumors using only a blood or fluid sample rather than a solid tissue biopsy.

Outcome Measures

Primary Outcome Measures :

1. recurrence [ Time Frame: 3 to 5 years ]
   Recurrence or metastasis of high-risk GIST after surgical resection followed by targeted drug therapy

Biospecimen Retention:   Samples With DNA

tumor tissues: collected from preoperative needle biopsy or specimens of surgical resection

blood tissues: venous blood collected at specific time point stipulated in the protocol

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

This study plans to invite patients with the following criteria: patients with resectable locally advanced GIST who received or did not receive neoadjuvant molecular targeted therapy, and patients with high recurrence risk grading by postoperative pathological assessment, including but not limited to the following clinical factors: Tumor Location, size, degree of mitoses, degree of tumor rupture, etc. Those who did not reach R0 resection or did not match the pathological staging, or who could not complete the test items required by the trial within the specified time due to the patient's non-cooperation, or who were deemed unsuitable by other investigators, would not be invited to participate in this study.

Criteria

Inclusion Criteria:

• Patients aged between 18 and 80
• Patients suspected for high-risk GIST by preoperative imaging examinations or diagnosed with high-risk GIST by pathological biopsy, who have not received preoperative neoadjuvant treatment
• Patients must have not received any treatment including radiotherapy, chemotherapy or surgery
• The function of other organs including liver and kidneys is good enough so that the patients could tolerate targeted therapy and surgery
• Postoperative pathology conformed the diagnosis of high-risk GIST
• Patients and their families could understand the protocol of this study and voluntarily agree to participate in. Signed informed consents are required

Exclusion Criteria:

• Previous medical history of malignant tumors or synchronous other malignancies
• Emergent surgery because of bowel obstruction, perforation or bleeding
• Pregnant or lactant women
• Medical history of severe mental illness
• Patients with contraindication for targeted therapy and surgery
• Non-R0 resection
• Postoperative pathology conformed the diagnosis of non-high-risk GIST
• Patients with distant metastasis
• Other situations in which researchers consider that the patient is unsuitable for this study

Contacts and Locations

Locations

China, Beijing

Peking University People'S Hospital; Recruiting

Beijing, Beijing, China, 100044

Contact: Shuya Yang 15210226300 15210226300@163.com

Sponsors and Collaborators

Peking University People's Hospital

Investigators

• Principal Investigator: Yingjiang Ye; Peking University People's Hospital

More Information

Publications of Results:

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• Responsible Party: YE Yingjiang, Director of the department of gastrointestinal surgery, Peking University People's Hospital
• ClinicalTrials.gov Identifier: NCT05408897
• Other Study ID Numbers: WCJZL202103
• First Posted: June 7, 2022
• Last Update Posted: September 21, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Gastrointestinal Stromal Tumors; Neoplasm, Residual; Recurrence; Disease Attributes; Pathologic Processes; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Neoplastic Processes