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

NCT05408897 | Recruiting

• 1 other identifier: WCJZL202103
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastrointestinal Stromal Tumors; Minimal Residual Disease

Outcome Measures

Primary Outcomes (1)

• recurrence

  Recurrence or metastasis of high-risk GIST after surgical resection followed by targeted drug therapy

  3 to 5 years

Interventions

liquid biopsy DIAGNOSTIC_TEST

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

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Peking University People's Hospital: lead

Study Sites (1)

Peking University People'S Hospital

Beijing, Beijing Municipality, 100044, China

RECRUITING

Related Publications (16)

• Connolly EM, Gaffney E, Reynolds JV. Gastrointestinal stromal tumours. Br J Surg. 2003 Oct;90(10):1178-86. doi: 10.1002/bjs.4352.

  PMID: 14515284 RESULT

• Tran T, Davila JA, El-Serag HB. The epidemiology of malignant gastrointestinal stromal tumors: an analysis of 1,458 cases from 1992 to 2000. Am J Gastroenterol. 2005 Jan;100(1):162-8. doi: 10.1111/j.1572-0241.2005.40709.x.

  PMID: 15654796 RESULT

• 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. doi: 10.1136/jcp.54.2.96.

  PMID: 11215292 RESULT

• Chan JK. Mesenchymal tumors of the gastrointestinal tract: a paradise for acronyms (STUMP, GIST, GANT, and now GIPACT), implication of c-kit in genesis, and yet another of the many emerging roles of the interstitial cell of Cajal in the pathogenesis of gastrointestinal diseases? Adv Anat Pathol. 1999 Jan;6(1):19-40. doi: 10.1097/00125480-199901000-00003.

  PMID: 10197236 RESULT

• 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. Science. 1998 Jan 23;279(5350):577-80. doi: 10.1126/science.279.5350.577.

  PMID: 9438854 RESULT

• 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. doi: 10.1016/s0016-5085(03)01046-1.

  PMID: 12949711 RESULT

• 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. doi: 10.1126/science.1079666. Epub 2003 Jan 9.

  PMID: 12522257 RESULT

• 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.

  PMID: 32293728 RESULT

• Cao F, Li A, Li J, Fang YU, Li F. Feasibility and safety of laparoscopic resection for gastric GISTs larger than 5 cm: Results from a prospective study. Oncol Lett. 2015 Oct;10(4):2081-2086. doi: 10.3892/ol.2015.3547. Epub 2015 Jul 30.

  PMID: 26622800 RESULT

• 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 (Baltimore). 2017 Apr;96(14):e6535. doi: 10.1097/MD.0000000000006535.

  PMID: 28383420 RESULT

• DeMatteo RP, Lewis JJ, Leung D, Mudan SS, Woodruff JM, Brennan MF. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg. 2000 Jan;231(1):51-8. doi: 10.1097/00000658-200001000-00008.

  PMID: 10636102 RESULT

• Dematteo RP, Gold JS, Saran L, Gonen 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 Feb 1;112(3):608-15. doi: 10.1002/cncr.23199.

  PMID: 18076015 RESULT

• 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 31.

  PMID: 18670422 RESULT

• 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, Vogelstein B, Gibbs P. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016 Jul 6;8(346):346ra92. doi: 10.1126/scitranslmed.aaf6219.

  PMID: 27384348 RESULT

• Garcia-Murillas I, Schiavon G, Weigelt B, Ng C, Hrebien S, Cutts RJ, Cheang M, Osin P, Nerurkar A, Kozarewa I, Garrido JA, Dowsett M, Reis-Filho JS, Smith IE, Turner NC. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med. 2015 Aug 26;7(302):302ra133. doi: 10.1126/scitranslmed.aab0021.

  PMID: 26311728 RESULT

• Abbosh C, Birkbak NJ, Wilson GA, Jamal-Hanjani M, Constantin T, Salari R, Le Quesne J, Moore DA, Veeriah S, Rosenthal R, Marafioti T, Kirkizlar E, Watkins TBK, McGranahan N, Ward S, Martinson L, Riley J, Fraioli F, Al Bakir M, Gronroos E, Zambrana F, Endozo R, Bi WL, Fennessy FM, Sponer N, Johnson D, Laycock J, Shafi S, Czyzewska-Khan J, Rowan A, Chambers T, Matthews N, Turajlic S, Hiley C, Lee SM, Forster MD, Ahmad T, Falzon M, Borg E, Lawrence D, Hayward M, Kolvekar S, Panagiotopoulos N, Janes SM, Thakrar R, Ahmed A, Blackhall F, Summers Y, Hafez D, Naik A, Ganguly A, Kareht S, Shah R, Joseph L, Marie Quinn A, Crosbie PA, Naidu B, Middleton G, Langman G, Trotter S, Nicolson M, Remmen H, Kerr K, Chetty M, Gomersall L, Fennell DA, Nakas A, Rathinam S, Anand G, Khan S, Russell P, Ezhil V, Ismail B, Irvin-Sellers M, Prakash V, Lester JF, Kornaszewska M, Attanoos R, Adams H, Davies H, Oukrif D, Akarca AU, Hartley JA, Lowe HL, Lock S, Iles N, Bell H, Ngai Y, Elgar G, Szallasi Z, Schwarz RF, Herrero J, Stewart A, Quezada SA, Peggs KS, Van Loo P, Dive C, Lin CJ, Rabinowitz M, Aerts HJWL, Hackshaw A, Shaw JA, Zimmermann BG; TRACERx consortium; PEACE consortium; Swanton C. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature. 2017 Apr 26;545(7655):446-451. doi: 10.1038/nature22364.

  PMID: 28445469 RESULT

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

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors; Neoplasm, Residual

Interventions

Liquid Biopsy

Condition Hierarchy (Ancestors)

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; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Investigative Techniques

Study Officials

• Yingjiang Ye

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the department of gastrointestinal surgery

Study Record Dates

• First Submitted: June 2, 2022
• First Posted: June 7, 2022
• Study Start: January 1, 2022
• Primary Completion: April 1, 2023
• Study Completion (Estimated): April 1, 2028
• Last Updated: September 21, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)