Short-course Radiotherapy Followed by Consolidation Chemotherapy. 2021-001206-29

NCT05253846 | Active Not Recruiting Phase 2

• 1 other identifier: ShorTrip
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

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.

Conditions

Locally Advanced Rectal Cancer

Keywords

FOLFOXIRI; Locally advanced rectal cancer; Short-course radiotherapy; Total neoadjuvant strategy

Outcome Measures

Primary Outcomes (1)

• complete pathologic response (pCR)

  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

  30 months

Secondary Outcomes (16)

• Overall toxicity rate

  30 months

• G3/4 toxicity rate

  30 months

• R0 Resection Rate

  30 months

• Failure-free survival (FFS)

  7 years

• Overall Survival (OS)

  7 years

Other Outcomes (1)

• Correlation of FFS and pCR with ctDNA status

  7 years

Study Arms (1)

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

Drug: Irinotecan; Drug: Oxaliplatin; Drug: Lederfolin; Drug: 5-Fluorouracil; Radiation: Short-course radiotherapy; Procedure: TME

Interventions

Irinotecan DRUG

chemotherapy treatment

SCRT--> FOLFOXIRI--> SURGERY

Oxaliplatin DRUG

chemotherapy treatment

SCRT--> FOLFOXIRI--> SURGERY

Lederfolin DRUG

treatment

SCRT--> FOLFOXIRI--> SURGERY

5-Fluorouracil DRUG

chemotherapy treatment

SCRT--> FOLFOXIRI--> SURGERY

Short-course radiotherapy RADIATION

RT

SCRT--> FOLFOXIRI--> SURGERY

TME PROCEDURE

surgery

SCRT--> FOLFOXIRI--> SURGERY

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• cT4
• tumor extending to within 1 mm of or beyond mesorectal fascia (i.e., circumferential radial margin threatened or involved)
• cT3, N1
• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Gruppo Oncologico del Nord-Ovest: lead

Study Sites (1)

U.O. Oncologia Medica 2 Universitaria - Azienda Ospedaliero-Universitaria Pisana Dipartimento di Ricerca Traslazionale e Nuove Tecnologie - University of Pisa

Pisa, 56126, Italy

Location

MeSH Terms

Interventions

Irinotecan; Oxaliplatin; Leucovorin; Fluorouracil

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Roberto Moretto, MD

  Azienda Ospedaliero, Universitaria Pisana

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2022
• First Posted: February 24, 2022
• Study Start: January 25, 2022
• Primary Completion: January 5, 2025
• Study Completion (Estimated): October 30, 2028
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)