Prospective Multicenter Clinical Study of Neoadjuvant Imatinib Mesylate for Gastrointestinal Stromal Tumors

Phase 2

Recruiting

• Conditions: Gastrointestinal Stromal Tumor; Progression-free Survival; Neoadjuvant
• Interventions: Drug: Imatinib

• Registration Number: NCT04933669
• Lead Sponsor: First Affiliated Hospital of Zhejiang University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-06-09
• Study First Submitted QC: 2021-06-18
• Study First Posted: 2021-06-22
• Study Start: 2021-09-07
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-09
• Last Update Posted: 2021-10-12
• Primary Completion: 2029-12-31
• Study Completion: 2029-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 122

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Imatinib neoadjuvant	Imatinib	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.

Primary Outcome Measures

Name	Time	Method
Progression free survival（PFS）	5 years	Progression free survival（PFS）

Secondary Outcome Measures

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

Trial Locations

Locations (1)

The First Affiliated Hospital, College of Medicine, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China