Clinical trial NCT05970900: 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）
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Gastrointestinal Stromal Tumor of Rectum
Keywords: Gastrointestinal Stromal Tumor
Rectum
Imatinib mesylate
c-KIT gene
Local resection
Lead sponsor: Fujian Medical University Union Hospital
Sponsor class: OTHER
First posted: 2023-08-01
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: Inclusion Criteria:

1. Over the age of 18.
2. Newly pathology-diagnosed rectal GIST
3. Tumor \> 2cm; local resection of R0 is not possible in the initial evaluation.
4. The lower margin of the tumor is ≤ 5cm from the anal verge.
5. C-KIT gene mutation.
6. Male or non-pregnant female.
7. ECOG score 0-2.
8. Did not receive targeted therapy before the start of the clinical trial.
9. 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.
10. The patient's informed consent has been obtained.

Exclusion Criteria:

1. Pathology is non-rectal GIST.
2. Under the age of 18.
3. Patients with distant metastasis.
4. 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.
5. 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.
6. The patient presents with severe and/or uncontrolled medical ailments, such as unmanaged diabetes, advanced chronic kidney disease, or active uncontrolled infection.
7. 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).
8. Subjects undergoing radiotherapy, chemotherapy, and/or targeted therapy.
9. Pregnant or lactating female patients.
10. Cognitive or psychiatric disorders.
11. Profound cardiac, hepatic, and renal dysfunction.
12. Non-adherence by the patient or the researchers' assessment of the patient's inability to complete the entire trial.

Primary outcomes:
measure: Organ preservation
timeFrame: 18 months
Secondary outcomes:
measure: 3-year disease-free survival
timeFrame: 36 months
measure: Local recurrence rate
timeFrame: 36 months
measure: Overall survival
timeFrame: 36 months
measure: R0 resection rate
timeFrame: 18 months
measure: Quality of life based on EORTC-QLQs-C30 and EORTC-QLQs-CR29
timeFrame: Baseline, 3 months, 12 months, 24 months, and 36 months after surgery
measure: Anorectal function
timeFrame: Baseline, 3 months, 12 months, 24 months, and 36 months after surgery
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: Weizhong Jiang
state: Fujian
Study officials:
affiliation: Fujian Medical University Union Hospital
name: Weizhong Jiang, MD
role: PRINCIPAL_INVESTIGATOR
References: