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

NCT05970900 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: 2023XHYG0025-01
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastrointestinal Stromal Tumor of Rectum

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 3-year disease-free survival

  36 months

• Local recurrence rate

  36 months

• Overall survival

  36 months

• R0 resection rate

  18 months

• Quality of life based on EORTC-QLQs-C30 and EORTC-QLQs-CR29

  Baseline, 3 months, 12 months, 24 months, and 36 months after surgery

Study Arms (1)

Preoperative Imatinib + local excision

EXPERIMENTAL

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: 1. Local transanal resection (TA) 2. Local resection transsacralapproach 3. Local resection via perineal approach 4. Local resection transvaginal approach

Drug: Imatinib Mesylate; Procedure: Local resection

Interventions

Imatinib Mesylate DRUG

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.

Also known as: Gleevec

Preoperative Imatinib + local excision

Local resection PROCEDURE

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

Preoperative Imatinib + local excision

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fujian Medical University Union Hospital: lead

Study Sites (1)

Weizhong Jiang

Fuzhou, Fujian, 350001, China

Location

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors; Piebaldism

Interventions

Imatinib Mesylate; Mastectomy, Segmental

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Albinism; Eye Diseases, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Skin Diseases, Genetic; Hypopigmentation; Pigmentation Disorders; Skin Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Mastectomy; Surgical Procedures, Operative

Study Officials

• Weizhong Jiang, MD

  Fujian Medical University Union Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Weizhong Jiang, MD

CONTACT

+8613763828825; Jiangwz362100@163.com

Jiabin Zheng

CONTACT

+8613365910080; xhyykjk@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: July 23, 2023
• First Posted: August 1, 2023
• Study Start: October 1, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2029
• Last Updated: August 1, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)