Prospective Multicenter Clinical Study of Neoadjuvant Imatinib Mesylate for Gastrointestinal Stromal Tumors (ZJGIST-01)

The R0 resection rate of gastrointestinal stromal tumor (GIST) with high recurrence risk was relatively low, and the relapse-free survival rate was relatively low, which needed to be further improved. A few retrospective analyses and a small sample of prospective studies have found that neoadjuvant therapy with imatinib mesylate can improve R0 resection rates. Whether neoadjuvant therapy prolongs long-term survival remains unclear. The primary objective of this study was to evaluate 5-year progression-free survival (PFS) for GIST patients with high recurrence risk after neoadjuvant treatment with imatinib mesylate.

Study Overview

• Status: Recruiting
• Conditions: Gastrointestinal Stromal Tumor; Progression-free Survival; Neoadjuvant
• Intervention / Treatment: Drug: Imatinib

• Study Type: Interventional
• Enrollment (Anticipated): 122
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Weili Yang, Doctor; Phone Number: +8613989879196; Email: yangweili@zju.edu.cn
• Study Contact Backup: Name: Jiren Yu; Phone Number: +8657187236147; Email: yujr0909@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The First Affiliated Hospital, College of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Preoperative histologically confirmed primary gastrointestinal stromal tumor
• Tumor must stain positive for c-Kit (CD117) and/or discovered on gist-1 (DOG-1) by immunohistochemistry
• Gene mutation test report including c-kit exons 9,11,13 and 17 and platelet-derived growth factor receptor alpha (PDGFRA) exons 12 and 18
• High risk GIST (as modified National Institutes of Health (NIH) 2008): stomach (maximum tumor diameter> 10.0cm), nonstomach (maximum tumor diameter> 5.0cm)
• Gender is not limited. Age: ≥ 18 years and ≤ 80 years old
• Performance status: Eastern Cooperative Oncology Group (ECOG) 0-1
• Patient had informed consent and signed a written consent form

Exclusion Criteria:

• Asp842Val (D842V) mutation in Exon 18 of PDGFRA gene, or wild type (c-kit exon 9,11,13,17, and PDGFRA Exon 12,18), or c-kit exon 9 mutation
• Treated with tyrosine kinase inhibitors including Imatinib
• Aspartate aminotransferase (AST) and/or Alanine aminotransferase (ALT)>2.5×ULN(upper limit of normal)，or Total bilirubin (TBIL)>1.5×ULN，or Creatinine (Cr)>1.0×ULN
• Absolute neutrophil count (ANC) < 1.5 × 10 ^ 9 / L；or Platelet count (PLT) < 75 × 10 ^ 9 / L；or Hemoglobin (Hb) ≥ 90 g / L
• Previous or concurrent other active malignant tumors (except for basal cell carcinoma of the skin, or cervical cancer in situ that has undergone curative therapy)
• Distant metastases are present
• Any of the following conditions during the 12 months prior to entry: myocardial infarction, severe / unstable angina, coronary artery / peripheral artery bypass surgery, symptomatic congestive heart failure, or cerebrovascular accidents
• positive Human Immunodeficiency Virus (HIV) antibody
• Currently participating in other clinical trials
• Pregnant or lactating women or have fertility without taking contraception
• Suffering from other serious acute and chronic physical or mental problems, or abnormal laboratory tests, will increase the risk of participation or drug use, or interfere with the judgment of the findings, judged by the researchers as participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Imatinib neoadjuvant; Patients receive oral imatinib mesylate 400mg once daily for 3-12 months in the absence of disease progression or unacceptable toxicity. Within 1 week after completion of preoperative imatinib mesylate, patients with responding or stable disease undergo surgical resection. After complete resection, patients receive oral imatinib mesylate 400mg once daily for 36 months in the absence of disease progression or unacceptable toxicity, and are followed for 5 years.

Drug: Imatinib; Imatinib neoadjuvant therapy; Other Names: neoadjuvant therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival（PFS）	Progression free survival（PFS）	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival（OS）	Overall survival（OS）	5 years
Objective Response Rate （ORR）	Rate of complete and partial response according to Choi criteria	Up to 1 year
R0 resection rate	complete resection rate with microscopically negative margin	Up to 1 year

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University
• Collaborators: Zhejiang Cancer Hospital; Second Affiliated Hospital, School of Medicine, Zhejiang University; Sir Run Run Shaw Hospital; First Affiliated Hospital of Wenzhou Medical University; Ningbo No. 1 Hospital; Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
• Investigators: Principal Investigator: Jiren Yu, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2021
• Primary Completion (Anticipated): December 31, 2029
• Study Completion (Anticipated): December 31, 2029

Study Registration Dates

• First Submitted: June 9, 2021
• First Submitted That Met QC Criteria: June 18, 2021
• First Posted (Actual): June 22, 2021

Study Record Updates

• Last Update Posted (Actual): October 12, 2021
• Last Update Submitted That Met QC Criteria: October 9, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: neoadjuvant; Gastrointestinal Stromal Tumors; Progression-free survival
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Disease Progression; Gastrointestinal Stromal Tumors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: IIT20210023C-R1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No