Efficacy and safety of short-course radiotherapy (SCRT) versus total neoadjuvant therapy in older patients with locally advanced rectal cancer: a multicentre, open-label, randomised pragmatic clinical trial
- Conditions
- MedDRA version: 21.0Level: PTClassification code: 10038049Term: Rectal cancer stage II Class: 100000004864locally advanced rectal cancerTherapeutic area: Diseases [C] - Neoplasms [C04]MedDRA version: 21.0Level: PTClassification code: 10038050Term: Rectal cancer stage III Class: 100000004864
- Registration Number
- CTIS2023-506703-26-00
- Lead Sponsor
- Institut Jules Bordet
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 264
Age = 70 years old, Signed Informed Consent form (ICF) obtained prior to any study related procedure., Male subjects with partners of childbearing potential must agree to use condom during the course of this study and for at least 6 months after the last administration of study drugs., ECOG performance status (PS): =1 if age > 75 years old, =2 if age = 75 years old, Histologically or cytologically confirmed adenocarcinoma of the rectum, Distal border of the tumour below the peritoneal reflection and within 15 cm of the anal verge, Operable stage III or high-risk stage II rectal cancer (high-risk tumours defined as those having =1 of the following features: T4, mesorectal fascia (MRF) involvement/threatening [i.e.,tumour within 1 mm of the MRF], extramural venous invasion). Patient with involvement of lateral pelvic lymph nodes are also eligible., Adequate bone marrow function as defined below: -Absolute neutrophil count =1,500/µL -Haemoglobin =9 g/dL -Platelets =100,000/µL, Adequate liver function as defined below: -Serum total bilirubin =1.5 x ULN. In case of known Gilbert’s syndrome <3xUNL is allowed -AST (SGOT) and ALT (SGPT) =2.5 x ULN -Alkaline phosphatase =2.5 x ULN, Adequate renal function as defined by estimated glomerular filtration rate (GFR) =30 mL/min/1.73m² (according to the CKD-EPI 2021 equation), Absence of clinical conditions that in the opinion of the investigator, would contraindicate neoadjuvant therapy and/or surgery.
Extensive growth into cranial part of the sacrum (above S2/3 junction) or the lumbosacral nerve roots indicating that surgery will never be possible even if substantial tumour down-sizing is achieved., Known dihydropyrimidine dehydrogenase (DPD) deficiency., Any previous treatment for rectal cancer, Presence of metastatic disease or recurrent rectal tumour., Presence of grade =2 peripheral neuropathy according to the Common Toxicity Criteria for Adverse Events (CTCAE) v.5.0., Significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the principal investigator’s opinion, may interfere with completion of the study., Any contraindication to pelvic irradiation as evaluated by the investigator., Known hypersensitivity reactions to the study drugs or to any excipients, premedications or non-investigational medicinal products or concomitant medications., Any investigational anti-cancer therapy other than the protocol specified therapies (participation in other prospective studies which do not imply any specific intervention may be allowed after discussion with the Study Chair)., Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment., Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure (grade III or IV as classified by the New York Heart Association), or serious cardiac arrhythmia requiring medication medication within the past 6 months.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary end point(s): The primary endpoint is Net Benefit Treatment, according to the following hierarchical outcome measures: 1.Overall survival at 3 years after randomisation 2.Progression-free survival at 3 years after randomisation 3.Increased-grade peripheral sensory neuropathy at 3 years after randomisation 4.Grade =3 toxicities during treatment;Main Objective: The primary objective of the trial is to demonstrate that a neoadjuvant treatment strategy of SCRT followed by surgery plus or minus adjuvant chemotherapy is a better trade-off between efficacy and safety than total neoadjuvant therapy (TNT) in an older rectal cancer population.;Secondary Objective: To assess short- and long-term efficacy of the study treatments, To assess safety and quality of life of the study treatments, To evaluate the impact of study treatments in terms of use of healthcare resources
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Safety of study treatments defined as the frequency of adverse events reported according to NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.;Secondary end point(s):Quality of Life based on EORTC-QLQ-C30, EORTC-QLQ-C29, EORTC-QLQ-CIPN20 and EQ-5Q-5L questionnaires;Secondary end point(s):Compliance to treatment;Secondary end point(s):Pathological complete response;Secondary end point(s):R0 resection;Secondary end point(s):Organ preservation;Secondary end point(s):Use of healthcare resources