search
Back to results

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

Primary Purpose

Gastrointestinal Stromal Tumor of Rectum

Status
Not yet recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Imatinib Mesylate
Local resection
Sponsored by
Fujian Medical University Union Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastrointestinal Stromal Tumor of Rectum focused on measuring Gastrointestinal Stromal Tumor, Rectum, Imatinib mesylate, c-KIT gene, Local resection

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Weizhong Jiang

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Preoperative Imatinib + local excision

Arm Description

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

Outcomes

Primary Outcome Measures

Organ preservation
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

3-year disease-free survival
The proportion of participants who remain disease-free at 3 years after surgery
Local recurrence rate
The local recurrence rate is defined as the incidence detection of a tumor involving the bowel wall only that occurs after LE or TME
Overall survival
The proportion of participants who remain survival at 3 years after surgery
R0 resection rate
The R0 resection rate is defined as the rate of R0 resection
Quality of life based on EORTC-QLQs-C30 and EORTC-QLQs-CR29
Quality of life accessed by EORTC-QLQs-C30 and EORTC-QLQs-CR29 questionnaire
Anorectal function
Anorectal function based on LARS score

Full Information

First Posted
July 23, 2023
Last Updated
July 23, 2023
Sponsor
Fujian Medical University Union Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT05970900
Brief Title
Preoperative Imatinib Mesylate Combined With Rectal-sparing Surgery in Patients With c-KIT Gene-mutant Rectal GIST
Acronym
PIRKER
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

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 1, 2023 (Anticipated)
Primary Completion Date
October 1, 2026 (Anticipated)
Study Completion Date
October 1, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fujian Medical University Union Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastrointestinal Stromal Tumor of Rectum
Keywords
Gastrointestinal Stromal Tumor, Rectum, Imatinib mesylate, c-KIT gene, Local resection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Preoperative Imatinib + local excision
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Imatinib Mesylate
Other Intervention Name(s)
Gleevec
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Local resection
Intervention Description
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
Primary Outcome Measure Information:
Title
Organ preservation
Description
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)
Time Frame
18 months
Secondary Outcome Measure Information:
Title
3-year disease-free survival
Description
The proportion of participants who remain disease-free at 3 years after surgery
Time Frame
36 months
Title
Local recurrence rate
Description
The local recurrence rate is defined as the incidence detection of a tumor involving the bowel wall only that occurs after LE or TME
Time Frame
36 months
Title
Overall survival
Description
The proportion of participants who remain survival at 3 years after surgery
Time Frame
36 months
Title
R0 resection rate
Description
The R0 resection rate is defined as the rate of R0 resection
Time Frame
18 months
Title
Quality of life based on EORTC-QLQs-C30 and EORTC-QLQs-CR29
Description
Quality of life accessed by EORTC-QLQs-C30 and EORTC-QLQs-CR29 questionnaire
Time Frame
Baseline, 3 months, 12 months, 24 months, and 36 months after surgery
Title
Anorectal function
Description
Anorectal function based on LARS score
Time Frame
Baseline, 3 months, 12 months, 24 months, and 36 months after surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Weizhong Jiang, MD
Phone
+8613763828825
Email
Jiangwz362100@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jiabin Zheng
Phone
+8613365910080
Email
xhyykjk@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Weizhong Jiang, MD
Organizational Affiliation
Fujian Medical University Union Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Weizhong Jiang
City
Fuzhou
State/Province
Fujian
ZIP/Postal Code
350001
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs