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）
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Organ preservation
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Over the age of
- •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-
- •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) <
- •5 × ULN, creatinine < 1.5×ULN, neutrophil count >
- •5 ×109 / L, platelet > 100 × 109 / L.
- •The patient's informed consent has been obtained.
排除标准
- •Pathology is non-rectal GIST.
- •Under the age of
- •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.
研究组 & 干预措施
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
干预措施: Imatinib Mesylate (Drug)
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
干预措施: Local resection (Procedure)
结局指标
主要结局
Organ preservation
时间窗: 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)
次要结局
- 3-year disease-free survival(36 months)
- Overall survival(36 months)
- Local recurrence rate(36 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)
- R0 resection rate(18 months)
- Anorectal function(Baseline, 3 months, 12 months, 24 months, and 36 months after surgery)
研究者
蒋伟忠
Associate professor
Fujian Medical University Union Hospital