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
Overview
- Phase
- Phase 2
- Intervention
- Irinotecan
- Conditions
- Locally Advanced Rectal Cancer
- Sponsor
- Gruppo Oncologico del Nord-Ovest
- Enrollment
- 63
- Locations
- 1
- Primary Endpoint
- complete pathologic response (pCR)
- Status
- Active, not recruiting
- Last Updated
- 10 months ago
Overview
Brief Summary
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.
Detailed Description
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)
Investigators
Eligibility Criteria
Inclusion Criteria
- •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);
Exclusion Criteria
- •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);
Arms & Interventions
SCRT--> FOLFOXIRI--> SURGERY
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
Intervention: Irinotecan
SCRT--> FOLFOXIRI--> SURGERY
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
Intervention: Oxaliplatin
SCRT--> FOLFOXIRI--> SURGERY
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
Intervention: Lederfolin
SCRT--> FOLFOXIRI--> SURGERY
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
Intervention: 5-Fluorouracil
SCRT--> FOLFOXIRI--> SURGERY
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
Intervention: Short-course radiotherapy
SCRT--> FOLFOXIRI--> SURGERY
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
Intervention: TME
Outcomes
Primary Outcomes
complete pathologic response (pCR)
Time Frame: 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
Secondary Outcomes
- 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)
- Quality of Life (QoL)(until 1 year after surgery)
- Failure-free survival (FFS)(7 years)
- Clinical complete response (cCR) rate(30 months)
- Surgical mortality(30 months)
- Rectal Continence(until 180 days after the ileostomy closure surgery)