NCT05253846进行中（未招募）2 期
Phase II Study of Short-course Radiotherapy Followed by Consolidation Chemotherapy With the Triplet FOLFOXIRI as Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: the ShorTrip Study
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 63
- 试验地点
- 2
- 主要终点
- complete pathologic response (pCR)
研究概览
简要总结
The aim of the ShorTrip trail is to evaluate the activity and the safety of total neoadjuvant strategy with FOLFOXIRI as consolidation therapy preceded by short-course radiotherapy and followed by surgery in LARC patients.
详细描述
This is a prospective, open-label, multicentre, phase II single arm trial. Eligible patients with middle-high LARC will receive short-course radiotherapy followed by consolidation chemotherapy with FOLFOXIRI and surgery.
The primary objective of this trial is to evaluate the rate of complete pathologic response (pCR)
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Written informed consent to study procedures and to translational analyses;
- •Age 18-70 years;
- •Histologically proven diagnosis of rectal adenocarcinoma;
- •Patients with locally advanced rectal cancer defined by the presence of at least one of the following features:
- •cN2 (defined as at least 4 positive lymphnodes at pelvic MRI)
- •tumor extending to within 1 mm of or beyond mesorectal fascia (i.e., circumferential radial margin threatened or involved)
- •Distal border of the tumour located between 5 and 12 cm from the anal verge (as measured by pelvic MRI);
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤1;
- •No evidence of metastatic disease by total body CT-scan;
- •Available tumour samples at baseline (archival biopsy);
- •Tumour amenable to curative resection (including pelvic exenteration);
- •No history of invasive rectal malignancy, regardless of disease-free interval;
- •No other rectal cancers (i.e., sarcoma, lymphoma, carcinoid, squamous cell carcinoma, or cloacogenic carcinoma) or synchronous colon cancer;
- •No clear involvement of the pelvic side walls by imaging;
- •Life expectancy of at least 5 years (excluding diagnosis of cancer);
- •Hematopoietic function: absolute neutrophil count ≥ 1,500/mm3; platelet count
- •≥100,000/mm3; haemoglobin level ≥ 9 g/dL;
- •Liver function: total bilirubin ≤ 1.5 times upper limit of normal (ULN); alkaline phosphatase ≤ 2 times ULN; AST ≤ 2 times ULN;
- •Renal function: creatinine clearance > 50 mL/min or serum creatinine 1.5 x UNL; no renal disease that would preclude study treatment or follow-up;
- •Women of childbearing potential must have a negative blood pregnancy test at the screening visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy.
- •However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient; - Subjects and their partners must be willing to avoid pregnancy during the trial. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception.
- •Contraception, starting during study screening visit throughout the study period up to 180 days after the last dose of chemotherapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject;
- •- Will and ability to comply with the protocol.
排除标准
- •Previous history of malignancy within the last 5 years will be excluded with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ;
- •Patients with radiological evidence of distant metastases;
- •Previous pelvic radiation therapy;
- •Symptomatic peripheral neuropathy > 2 grade NCIC-CTG criteria;
- •Previous treatment with fluoropyrimidine and/or oxaliplatin and/or irinotecan;
- •Patient with complete dihydropyrimidine dehydrogenase (DPYD) deficiency (homozygous of the following DPYD polymorphisms: c1679GG, c1905+1AA, c2846TT);
- •Treatment with any investigational drug within 30 days prior to enrolment or 2 investigational agent half-lives (whichever is longer);
- •Active uncontrolled infections or other clinically relevant concomitant illness contraindicating chemotherapy administration;
- •Clinically significant (e.g. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF), serious cardiac arrhythmia requiring medication;
- •Active inflammatory bowel disease (i.e., patients requiring current medical interventions or who are symptomatic);
- •Partial or total colectomy;
- •Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study and until 180 days after the last trial treatment;
- •Known hypersensitivity to fluorouracil, oxaliplatin or irinotecan;
- •Psychiatric or addictive disorders, or other conditions that, in the opinion of the investigator, would preclude study participation;
- •Active uncontrolled infections or other clinically relevant concomitant illness contraindicating chemotherapy administration;
- •Withdrawal of the consent to take part to the study.
研究组 & 干预措施
SCRT--> FOLFOXIRI--> SURGERY
Experimental
SHORT-COURSE RT
FOLFOXIRI
- IRINOTECAN 165 mg/sqm iv over 60 minutes, day 1 followed by
- OXALIPLATIN 85 mg/sqm iv over 2 hours, day 1 in two-way with
- LEDERFOLIN 200 mg/sqm iv over 2 hours, day 1 followed by
- 5-FLUOROURACIL 3200 mg/sqm 48 h-continuous infusion, starting on day 1. The chemotherapy treatment will be repeated every 2 weeks up to 8 cycles.
Surgery with TME should be performed after 4 weeks after the last cycle of chemotherapy
干预措施: Irinotecan (Drug)
SCRT--> FOLFOXIRI--> SURGERY
Experimental
SHORT-COURSE RT
FOLFOXIRI
- IRINOTECAN 165 mg/sqm iv over 60 minutes, day 1 followed by
- OXALIPLATIN 85 mg/sqm iv over 2 hours, day 1 in two-way with
- LEDERFOLIN 200 mg/sqm iv over 2 hours, day 1 followed by
- 5-FLUOROURACIL 3200 mg/sqm 48 h-continuous infusion, starting on day 1. The chemotherapy treatment will be repeated every 2 weeks up to 8 cycles.
Surgery with TME should be performed after 4 weeks after the last cycle of chemotherapy
干预措施: Oxaliplatin (Drug)
SCRT--> FOLFOXIRI--> SURGERY
Experimental
SHORT-COURSE RT
FOLFOXIRI
- IRINOTECAN 165 mg/sqm iv over 60 minutes, day 1 followed by
- OXALIPLATIN 85 mg/sqm iv over 2 hours, day 1 in two-way with
- LEDERFOLIN 200 mg/sqm iv over 2 hours, day 1 followed by
- 5-FLUOROURACIL 3200 mg/sqm 48 h-continuous infusion, starting on day 1. The chemotherapy treatment will be repeated every 2 weeks up to 8 cycles.
Surgery with TME should be performed after 4 weeks after the last cycle of chemotherapy
干预措施: 5-Fluorouracil (Drug)
SCRT--> FOLFOXIRI--> SURGERY
Experimental
SHORT-COURSE RT
FOLFOXIRI
- IRINOTECAN 165 mg/sqm iv over 60 minutes, day 1 followed by
- OXALIPLATIN 85 mg/sqm iv over 2 hours, day 1 in two-way with
- LEDERFOLIN 200 mg/sqm iv over 2 hours, day 1 followed by
- 5-FLUOROURACIL 3200 mg/sqm 48 h-continuous infusion, starting on day 1. The chemotherapy treatment will be repeated every 2 weeks up to 8 cycles.
Surgery with TME should be performed after 4 weeks after the last cycle of chemotherapy
干预措施: TME (Procedure)
SCRT--> FOLFOXIRI--> SURGERY
Experimental
SHORT-COURSE RT
FOLFOXIRI
- IRINOTECAN 165 mg/sqm iv over 60 minutes, day 1 followed by
- OXALIPLATIN 85 mg/sqm iv over 2 hours, day 1 in two-way with
- LEDERFOLIN 200 mg/sqm iv over 2 hours, day 1 followed by
- 5-FLUOROURACIL 3200 mg/sqm 48 h-continuous infusion, starting on day 1. The chemotherapy treatment will be repeated every 2 weeks up to 8 cycles.
Surgery with TME should be performed after 4 weeks after the last cycle of chemotherapy
干预措施: Lederfolin (Drug)
SCRT--> FOLFOXIRI--> SURGERY
Experimental
SHORT-COURSE RT
FOLFOXIRI
- IRINOTECAN 165 mg/sqm iv over 60 minutes, day 1 followed by
- OXALIPLATIN 85 mg/sqm iv over 2 hours, day 1 in two-way with
- LEDERFOLIN 200 mg/sqm iv over 2 hours, day 1 followed by
- 5-FLUOROURACIL 3200 mg/sqm 48 h-continuous infusion, starting on day 1. The chemotherapy treatment will be repeated every 2 weeks up to 8 cycles.
Surgery with TME should be performed after 4 weeks after the last cycle of chemotherapy
干预措施: Short-course radiotherapy (Radiation)
结局指标
主要结局
complete pathologic response (pCR)
时间窗: 30 months
Pathological complete response rate, defined as the percentage of patients, relative to the total of enrolled subjects, with the absence of residual tumour cells in the resected specimens. pCR will be assessed by tumour regression grade according to Dworak et al, at the histopathological exam
次要结局
- G3/4 toxicity rate(30 months)
- Overall Survival (OS)(7 years)
- Overall toxicity rate(30 months)
- R0 Resection Rate(30 months)
- Time to distant metastases(7 years)
- Major pathological response (MPR) rate(30 months)
- Time to locoregional failure(7 years)
- Surgical morbidities(30 months)
- Failure-free survival (FFS)(7 years)
- Clinical complete response (cCR) rate(30 months)
- Surgical mortality(30 months)
- Quality of Life (QoL)(until 1 year after surgery)
- Rectal Continence(until 180 days after the ileostomy closure surgery)
研究者
研究点 (2)
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