Preoperative Imatinib Mesylate Combined With Rectal-sparing Surgery in Patients With c-KIT Gene-mutant Rectal GIST

Official title

Preoperative Imatinib Mesylate Combined With Rectal-sparing Surgery in Patients With c-KIT Gene-mutant Rectal GIST: an Open-label, Single-arm, Phase III Trial（PIRKER）

Overview

Prior to the implementation of preoperative imatinib mesylate therapy, a considerable percentage (ranging from 34.5% to 67.5%) of individuals diagnosed with rectal gastrointestinal stromal tumors (GIST) underwent abdominoperineal resection (APR), a surgical procedure that involved the removal of the anus and necessitated a permanent colostomy. This study aims to investigate the safety and viability of an organ-preserving approach involving preoperative imatinib mesylate treatment in conjunction with local resection for rectal GIST, specifically targeting patients with c-KIT gene mutations.

Detailed description

Prior to the implementation of preoperative imatinib mesylate therapy, a considerable percentage (ranging from 34.5% to 67.5%) of individuals diagnosed with rectal gastrointestinal stromal tumors (GIST) underwent abdominoperineal resection (APR), a surgical procedure that involved the removal of the anus and necessitated a permanent colostomy.

Previous studies have established that preoperative administration of imatinib mesylate effectively diminishes the size of rectal gastrointestinal stromal tumors (GIST) and enhances the likelihood of sphincter preservation. After initiating preoperative imatinib mesylate treatment, the sphincter preservation rate has notably escalated from 4.2% to 33.0%-94.9%.

In theory, lymph node resection is not required for Gastrointestinal Stromal Tumors (GIST); the local excision of rectal GIST enables sphincter preservation and yields satisfactory anal function and quality of life (QoL). Various surgical techniques are utilized for local excision, including traditional transanal (TA) and transanal minimally invasive surgery (TAMIS) approaches.

This study aims to explore the safety and feasibility of an organ-preservation strategy of preoperative imatinib mesylate combined with local resection in rectal gastrointestinal stromal tumor (GIST), specifically for patients with c-KIT gene mutations.

Interventions

• Drug Imatinib Mesylate
  1. For patients with c-KIT exon 11 mutation, imatinib mesylate, 400mg, qd. 2. For patients with c-KIT exon 9 mutation, imatinib mesylate, 600mg or 800mg, qd.
• Procedure Local resection
  According to the characteristics of the location of the tumor, the surgeon decides the surgical approach based on the existing literature and the availability of surgical equipment, including: 1. Local transanal resection (TA) 2. Local resection transsacralapproach 3. Local resection via perineal approach 4. Local resection transvaginal approach

Primary outcome measures

• Organ preservation [Time frame: 18 months]

Secondary outcome measures (6)

• 3-year disease-free survival [Time frame: 36 months]
• Local recurrence rate [Time frame: 36 months]
• Overall survival [Time frame: 36 months]
• R0 resection rate [Time frame: 18 months]
• Quality of life based on EORTC-QLQs-C30 and EORTC-QLQs-CR29 [Time frame: Baseline, 3 months, 12 months, 24 months, and 36 months after surgery]
• Anorectal function [Time frame: Baseline, 3 months, 12 months, 24 months, and 36 months after surgery]

Eligibility criteria

Inclusion criteria

• Over the age of 18.
• Newly pathology-diagnosed rectal GIST
• Tumor > 2cm; local resection of R0 is not possible in the initial evaluation.
• The lower margin of the tumor is ≤ 5cm from the anal verge.
• C-KIT gene mutation.
• Male or non-pregnant female.
• ECOG score 0-2.
• Did not receive targeted therapy before the start of the clinical trial.
• Sufficient organ functions are defined as follows:

Total bilirubin < 1.5×ULN (upper limit of normal, ULN), serum AST (SGOT) and ALT (SGPT) < 2. 5 × ULN, creatinine < 1.5×ULN, neutrophil count > 1. 5 ×109 / L, platelet > 100 × 109 / L.

• The patient's informed consent has been obtained.

Exclusion criteria

• Pathology is non-rectal GIST.
• Under the age of 18.
• Patients with distant metastasis.
• The patient is not permitted to have additional primary malignant tumors within five years unless those tumors are currently deemed clinically insignificant and do not necessitate active intervention, such as basal cell skin cancer or cervical cancer in situ. The presence of any other malignant diseases is strictly prohibited.
• Individuals diagnosed with stage III or IV cardiac conditions, specifically congestive heart failure and myocardial infarction occurring within six months prior to the commencement of the study.
• The patient presents with severe and/or uncontrolled medical ailments, such as unmanaged diabetes, advanced chronic kidney disease, or active uncontrolled infection.
• Co-administration of imatinib with warfarin or acetaminophen is contraindicated, necessitating the substitution of alternative medications (e.g., low molecular weight heparin in place of warfarin).
• Subjects undergoing radiotherapy, chemotherapy, and/or targeted therapy.
• Pregnant or lactating female patients.
• Cognitive or psychiatric disorders.
• Profound cardiac, hepatic, and renal dysfunction.
• Non-adherence by the patient or the researchers' assessment of the patient's inability to complete the entire trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Weizhong Jiang — Fuzhou

Identifiers

NCT: NCT05970900 · 2023XHYG0025-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗