CAPECITABINE for Locally advanced rectal cancer | Rectal cancer stage III | Rectal cancer stage II

Inclusion criteria

• {"criterion_text":"- Age ≥ 70 years old\n- ECOG performance status (PS): ≤1 if age > 75 years old, ≤2 if age ≤ 75 years old\n- Histologically or cytologically confirmed adenocarcinoma of the rectum\n- Distal border of the tumour below the peritoneal reflection and within 15 cm of the anal verge\n- 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.\n- Adequate bone marrow function as defined below: -\tAbsolute neutrophil count ≥1,500/µL -\tHaemoglobin ≥9 g/dL -\tPlatelets ≥100,000/µL\n- Adequate liver function as defined below: -\tSerum total bilirubin ≤1.5 x ULN. In case of known Gilbert’s syndrome <3xUNL is allowed -\tAST (SGOT) and ALT (SGPT) ≤2.5 x ULN -\tAlkaline phosphatase ≤2.5 x ULN\n- Adequate renal function as defined by estimated glomerular filtration rate (GFR) ≥30 mL/min/1.73m² (according to the CKD-EPI 2021 equation)\n- Absence of clinical conditions that in the opinion of the investigator, would contraindicate neoadjuvant therapy and/or surgery.\n- Signed Informed Consent form (ICF) obtained prior to any study related procedure.\n- 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."}

Exclusion criteria

• {"criterion_text":"- 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.\n- Complete dihydropyrimidine dehydrogenase (DPD) deficiency.\n- Any previous treatment for rectal cancer\n- Presence of metastatic disease or recurrent rectal tumour.\n- Presence of grade ≥2 peripheral neuropathy according to the Common Toxicity Criteria for Adverse Events (CTCAE) v.5.0.\n- 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.\n- Any contraindication to pelvic irradiation as evaluated by the investigator.\n- Known hypersensitivity reactions to the study drugs or to any excipients, premedications or non-investigational medicinal products or concomitant medications.\n- 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).\n- Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment.\n- 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.\n- Use of brivudine, sorivudine or their chemically related analogues."}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is Net Benefit Treatment, according to the following hierarchical outcome measures: 1.\tOverall survival at 3 years after randomisation 2.\tProgression-free survival at 3 years after randomisation 3.\tIncreased-grade peripheral sensory neuropathy at 3 years after randomisation 4.\tGrade ≥3 toxicities during treatment","definition_or_measurement_approach":"Hierarchical outcome assessed as Net Benefit Treatment with the following measures: overall survival at 3 years after randomisation; progression-free survival at 3 years after randomisation; increased-grade peripheral sensory neuropathy at 3 years after randomisation; and grade ≥3 toxicities during treatment (toxicity grading per CTCAE v5.0 where applicable)."}

Secondary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Frequency of adverse events as reported and graded according to NCI CTCAE v5.0."}
• {"endpoint_text":"- Quality of Life based on EORTC-QLQ-C30, EORTC-QLQ-C29, EORTC-QLQ-CIPN20 and EQ-5Q-5L questionnaires","definition_or_measurement_approach":"Patient-reported quality-of-life measured using EORTC-QLQ-C30, QLQ-C29, QLQ-CIPN20 and EQ-5D-5L instruments (questionnaires specified in protocol)."}
• {"endpoint_text":"- Compliance to treatment","definition_or_measurement_approach":"Assessment of adherence/compliance to the assigned treatment regimen (methodology per protocol)."}
• {"endpoint_text":"- Pathological complete response","definition_or_measurement_approach":"Pathological assessment of tumour response (pathological complete response as defined in protocol/pathology criteria)."}
• {"endpoint_text":"- R0 resection","definition_or_measurement_approach":"Surgical/pathology report indicating R0 resection status (no residual tumour at resection margins)."}
• {"endpoint_text":"- Organ preservation","definition_or_measurement_approach":"Assessment of organ preservation (e.g., avoidance of radical surgery) as defined in the protocol."}
• {"endpoint_text":"- Use of healthcare resources","definition_or_measurement_approach":"Health-economic/resource use assessments as defined in the protocol."}

Belgium

Earliest CTIS Part Ii Submission Date

24-11-2023

Latest Decision Or Authorization Date

29-10-2025

Processing Time Days

705

Number Of Sites

26

Number Of Participants

264

Primary sponsor

Full Name

Institut Jules Bordet

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Belgium

Third parties

• {"country":"","full_name":"Belgian Health Care Knowledge Centre (KCE)","duties_or_roles":"Source of monetary support","organisation_type":""}