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

Gastrointestinal Stromal Tumor of Rectum Clinical Trial

— 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）

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05970900
• Other study ID #: 2023XHYG0025-01
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: October 1, 2023
• Est. completion date: October 1, 2029

Study information

• Verified date: July 2023
• Source: Fujian Medical University Union Hospital
• Contact: Weizhong Jiang, MD
• Phone: +8613763828825
• Email: Jiangwz362100[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 23
• Est. completion date: October 1, 2029
• Est. primary completion date: October 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumor of Rectum
• Gastrointestinal Stromal Tumors

Intervention

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.

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

Locations

Country	Name	City	State
China	Weizhong Jiang	Fuzhou	Fujian

Sponsors (1)

Lead Sponsor	Collaborator
Fujian Medical University Union Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	18 months
Secondary	3-year disease-free survival	The proportion of participants who remain disease-free at 3 years after surgery	36 months
Secondary	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	36 months
Secondary	Overall survival	The proportion of participants who remain survival at 3 years after surgery	36 months
Secondary	R0 resection rate	The R0 resection rate is defined as the rate of R0 resection	18 months
Secondary	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	Baseline, 3 months, 12 months, 24 months, and 36 months after surgery
Secondary	Anorectal function	Anorectal function based on LARS score	Baseline, 3 months, 12 months, 24 months, and 36 months after surgery