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

Gastrointestinal Stromal Tumors Clinical Trial

Official title:

Prediction of Postoperative Treatment Efficacy and Recurrence Risk of High-risk GIST Based on Minimal Residual Disease Detected by Liquid Biopsy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05408897
• Other study ID #: WCJZL202103
• Status: Recruiting
• Start date: January 1, 2022
• Est. completion date: April 2028

Study information

• Verified date: September 2022
• Source: Peking University People's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: April 2028
• Est. primary completion date: April 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumors
• Minimal Residual Disease
• Neoplasm, Residual
• Recurrence

Intervention

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.

Locations

Country	Name	City	State
China	Peking University People'S Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University People's Hospital

Country where clinical trial is conducted

China, 

References & Publications (16)

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Connolly EM, Gaffney E, Reynolds JV. Gastrointestinal stromal tumours. Br J Surg. 2003 Oct;90(10):1178-86. Review. — View Citation

Dematteo RP, Gold JS, Saran L, Gönen M, Liau KH, Maki RG, Singer S, Besmer P, Brennan MF, Antonescu CR. Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST). Cancer. 2008 — View Citation

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Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, Thornton K, Agrawal N, Sokoll L, Szabo SA, Kinzler KW, Vogelstein B, Diaz LA Jr. Circulating mutant DNA to assess tumor dynamics. Nat Med. 2008 Sep;14(9):985-90. doi: 10.1038/nm.1789. Epub 2007 Jul — View Citation

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Graadt van Roggen JF, van Velthuysen ML, Hogendoorn PC. The histopathological differential diagnosis of gastrointestinal stromal tumours. J Clin Pathol. 2001 Feb;54(2):96-102. Review. — View Citation

Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, Singer S, Griffith DJ, Haley A, Town A, Demetri GD, Fletcher CD, Fletcher JA. PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003 Jan 31;299(5607):708-10. Epub — View Citation

Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, Kawano K, Hanada M, Kurata A, Takeda M, Muhammad Tunio G, Matsuzawa Y, Kanakura Y, Shinomura Y, Kitamura Y. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. — View Citation

Hirota S, Ohashi A, Nishida T, Isozaki K, Kinoshita K, Shinomura Y, Kitamura Y. Gain-of-function mutations of platelet-derived growth factor receptor alpha gene in gastrointestinal stromal tumors. Gastroenterology. 2003 Sep;125(3):660-7. — View Citation

Huang CM, Chen QF, Lin JX, Lin M, Zheng CH, Li P, Xie JW, Wang JB, Lu J, Chen QY, Cao LL, Tu RH. Can laparoscopic surgery be applied in gastric gastrointestinal stromal tumors located in unfavorable sites?: A study based on the NCCN guidelines. Medicine ( — View Citation

Li J, Shen L. The current status of and prospects in research regarding gastrointestinal stromal tumors in China. Cancer. 2020 May 1;126 Suppl 9:2048-2053. doi: 10.1002/cncr.32684. Review. — View Citation

Tie J, Wang Y, Tomasetti C, Li L, Springer S, Kinde I, Silliman N, Tacey M, Wong HL, Christie M, Kosmider S, Skinner I, Wong R, Steel M, Tran B, Desai J, Jones I, Haydon A, Hayes T, Price TJ, Strausberg RL, Diaz LA Jr, Papadopoulos N, Kinzler KW, Vogelste — View Citation

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* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	recurrence	Recurrence or metastasis of high-risk GIST after surgical resection followed by targeted drug therapy	3 to 5 years