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

• ClinicalTrials.gov Identifier: NCT05970900
• Recruitment Status: Not yet recruiting
• First Posted: August 1, 2023
• Last Update Posted: August 1, 2023
• Sponsor: Fujian Medical University Union Hospital
• Information provided by (Responsible Party): 蒋伟忠, Fujian Medical University Union Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Gastrointestinal Stromal Tumor of Rectum	Drug: Imatinib Mesylate; Procedure: Local resection	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 23 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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）
• Estimated Study Start Date: October 1, 2023
• Estimated Primary Completion Date: October 1, 2026
• Estimated Study Completion Date: October 1, 2029

Arms and Interventions

Arm

Intervention/treatment

Experimental: Preoperative Imatinib + local excision; Following the attainment of the maximum treatment response through imatinib mesylate administration, typically occurring within 6-12 months, as evidenced by two consecutive imaging evaluations, the tumor exhibited no further reduction in size, thus necessitating the selection of surgical intervention. 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: Local transanal resection (TA); Local resection transsacralapproach; Local resection via perineal approach; Local resection transvaginal approach

Drug: Imatinib Mesylate; For patients with c-KIT exon 11 mutation, imatinib mesylate, 400mg, qd.; For patients with c-KIT exon 9 mutation, imatinib mesylate, 600mg or 800mg, qd.; Other Name: Gleevec; 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: Local transanal resection (TA); Local resection transsacralapproach; Local resection via perineal approach; Local resection transvaginal approach

Outcome Measures

Primary Outcome Measures :

1. Organ preservation [ Time Frame: 18 months ]
   Rectum intact, owing to no total mesorectal excision (TME), no locoregional regrowth unless amenable to limited, curative (R0) salvage surgery by local excision (LE) and no permanent stoma (including a never reversed protective stoma, or a stoma owing to toxicities and/or poor functional outcomes)

Secondary Outcome Measures :

1. 3-year disease-free survival [ Time Frame: 36 months ]
   The proportion of participants who remain disease-free at 3 years after surgery
2. Local recurrence rate [ Time Frame: 36 months ]
   The local recurrence rate is defined as the incidence detection of a tumor involving the bowel wall only that occurs after LE or TME
3. Overall survival [ Time Frame: 36 months ]
   The proportion of participants who remain survival at 3 years after surgery
4. R0 resection rate [ Time Frame: 18 months ]
   The R0 resection rate is defined as the rate of R0 resection
5. 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 ]
   Quality of life accessed by EORTC-QLQs-C30 and EORTC-QLQs-CR29 questionnaire
6. Anorectal function [ Time Frame: Baseline, 3 months, 12 months, 24 months, and 36 months after surgery ]
   Anorectal function based on LARS score

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Weizhong Jiang, MD; +8613763828825; Jiangwz362100@163.com

Contact: Jiabin Zheng; +8613365910080; xhyykjk@163.com

Locations

China, Fujian

Weizhong Jiang

Fuzhou, Fujian, China, 350001

Sponsors and Collaborators

Fujian Medical University Union Hospital

Investigators

• Principal Investigator: Weizhong Jiang, MD; Fujian Medical University Union Hospital

More Information

• Responsible Party: 蒋伟忠, Associate professor, Fujian Medical University Union Hospital
• ClinicalTrials.gov Identifier: NCT05970900
• Other Study ID Numbers: 2023XHYG0025-01
• First Posted: August 1, 2023
• Last Update Posted: August 1, 2023
• Last Verified: July 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by 蒋伟忠, Fujian Medical University Union Hospital:

Gastrointestinal Stromal Tumor; Rectum; Imatinib mesylate; c-KIT gene; Local resection

Additional relevant MeSH terms:

Gastrointestinal Stromal Tumors; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Imatinib Mesylate; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents