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

NCT ID: NCT05253846

Last Updated: 2025-06-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-25
• Study Completion Date: 2028-10-30

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)

Conditions

Locally Advanced Rectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Irinotecan

Intervention Type: DRUG

chemotherapy treatment

Oxaliplatin

Intervention Type: DRUG

chemotherapy treatment

Lederfolin

Intervention Type: DRUG

treatment

5-Fluorouracil

Intervention Type: DRUG

chemotherapy treatment

Short-course radiotherapy

Intervention Type: RADIATION

RT

TME

Intervention Type: PROCEDURE

surgery

Interventions

Irinotecan

chemotherapy treatment

Intervention Type: DRUG

Oxaliplatin

chemotherapy treatment

Intervention Type: DRUG

Lederfolin

treatment

Intervention Type: DRUG

5-Fluorouracil

chemotherapy treatment

Intervention Type: DRUG

Short-course radiotherapy

RT

Intervention Type: RADIATION

TME

surgery

Intervention Type: PROCEDURE

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)
• 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;
• 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.

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);
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Gruppo Oncologico del Nord-Ovest

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roberto Moretto, MD

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliero, Universitaria Pisana

Locations

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

Pisa, , Italy

Countries

Italy

Other Identifiers

ShorTrip

Identifier Type: -

Identifier Source: org_study_id