OXALIPLATIN for Locally advanced rectal cancer

Inclusion criteria

• {"criterion_text":"- 18 years or older\n- WHO performance score 0-1\n- Fit for (modified dose) triple chemotherapy (FOLFOXIRI)\n- Histopathological confirmed rectal cancer\n- Confirmed high-risk locally advanced rectal cancer, at high risk of treatment failure, meeting one of the following imaging-based criteria: cT4b or evident tumour invasion of the MRF, EMVI grade IV, tumour deposits, bilateral or extensive unilateral extramesorectal lymph nodes ≥ 7mm\n- Resectable disease as determined on magnetic resonance imaging (MRI) or deemed resectable disease after neoadjuvant treatment\n- Expected gross incomplete resection with overt tumour remaining in the patient after resection, tumour invasion in the neuroforamina, encasement of the ischiatic nerve and invasion of the cortex from S2 and upwards are considered not resectable\n- Written informed consent"}

Exclusion criteria

• {"criterion_text":"- Evidence of metastatic disease at time of inclusion or within six months prior to inclusion except for patients with enlarged iliac or inguinal lymph nodes and non-specific lung noduli\n- Homozygous DPD deficiency\n- Any chemotherapy within the past 6 months\n- Any contraindication for the planned systemic therapy (e.g., severe allergy, pregnancy, kidney dysfunction and thrombocytopenia), as determined by the medical oncologist\n- Previous radiotherapy in the pelvic area precluding chemoradiotherapy with a dose of 50 – 50.4 Gy\n- Any contraindication for the planned chemoradiotherapy (e.g., severe allergy to the chemotherapy agent or no possibility to receive radiotherapy), as determined by the medical oncologist and/or radiation oncologist\n- Any contraindication to undergo surgery, as determined by the surgeon and/or anaesthesiologist\n- Concurrent malignancies that interfere with the planned study treatment or the prognosis of the resected tumour\n- Microsatellite instability (MSI)"}

Primary endpoints

• {"endpoint_text":"- pCR post operatively: The pathological response is evaluated by an experienced pathologist in one of the participating centres and noted in the patient’s medical file. A pathological complete response is defined as the absence of residual tumour cells in the complete resected specimen including all resected regional lymph nodes (ypT0N0) according to the 8th edition of the UICC TNM classification of malignant tumours.","definition_or_measurement_approach":"Pathological response evaluated by an experienced pathologist at a participating centre and recorded in the patient's medical file; pCR defined as absence of residual tumour cells in the complete resected specimen including all resected regional lymph nodes (ypT0N0) per UICC TNM 8th edition."}
• {"endpoint_text":"- cCR at 1 year: The clinical response is evaluated by an experienced radiologist in one of the participating centres and noted in the patients’ medical file. A cCR is defined as the absence of viable tumour tissue based on magnetic resonance imaging and endoscopic evaluation. In case of a sustained cCR at 1 year, there is no regrowth or viable tumour tissue present on magnetic resonance imaging and endoscopy 1 year after the last day of chemoradiotherapy.","definition_or_measurement_approach":"Clinical response evaluated by an experienced radiologist and recorded in the patient's medical file; cCR defined as absence of viable tumour tissue by MRI and endoscopic evaluation with no regrowth at 1 year after last day of chemoradiotherapy."}

Secondary endpoints

• {"endpoint_text":"- Regrowth free survival at 3 and 5 years. Regrowth is defined as endoluminal or locoregional nodal recurrence after cCR in a watch and wait approach.","definition_or_measurement_approach":"Regrowth confirmed as endoluminal or locoregional nodal recurrence after cCR; survival assessed at 3 and 5 years."}
• {"endpoint_text":"- Local recurrence free survival at 3 and 5 years. Local recurrence is defined as locoregional recurrence after TME-surgery. Local recurrence is confirmed by either radiological or histopathological examination.","definition_or_measurement_approach":"Local recurrence confirmation by radiological or histopathological examination; survival measured at 3 and 5 years."}
• {"endpoint_text":"- Distant metastasis free survival at 3 and 5 years. Distant metastasis is confirmed by either radiological or histopathological examination.","definition_or_measurement_approach":"Distant metastasis confirmation by radiological or histopathological examination; survival measured at 3 and 5 years."}
• {"endpoint_text":"- Progression free survival at 3 and 5 years. Progression is defined as progression of the primary tumour, local recurrence or distant metastases, confirmed by radiological or histopathological examination or death.","definition_or_measurement_approach":"Progression confirmed by radiological or histopathological exam or death; PFS measured at 3 and 5 years."}
• {"endpoint_text":"- Disease free survival (DFS) at 3 and 5 years. DFS is defined as no confirmed signs of local recurrence, distant metastases or death.","definition_or_measurement_approach":"DFS measured as absence of confirmed local recurrence, distant metastases or death at 3 and 5 years."}
• {"endpoint_text":"- Overall survival at 3 and 5 years.","definition_or_measurement_approach":"Overall survival measured at 3 and 5 years."}
• {"endpoint_text":"- Successful organ preservation at 1 and 3 years. Organ preservation is considered to have failed if the rectum is removed; if the patient develops an unequivocal locoregional cancer recurrence or if the patient has a stoma.","definition_or_measurement_approach":"Organ preservation assessed at 1 and 3 years; failure defined as rectum removal, unequivocal locoregional recurrence, or presence of a stoma."}
• {"endpoint_text":"- Radiological response after induction chemotherapy. Assessment and reporting of all MRI scans is performed by the radiologist according to a standard operating procedure and is registered in the patient’s medical file.","definition_or_measurement_approach":"Radiological response assessed by radiologist per SOP and recorded in medical file (MRI assessments)."}
• {"endpoint_text":"- Radiological response after chemoradiotherapy. Assessment and reporting of all MRI scans is performed by the radiologist according to a standard operating procedure and is registered in the patient’s medical file.","definition_or_measurement_approach":"Radiological response after chemoradiotherapy assessed by radiologist per SOP and recorded in medical file (MRI assessments)."}
• {"endpoint_text":"- Pathological response as determined by Mandard grading system. The Mandard score is registered by the pathologist in the patient's medical file.","definition_or_measurement_approach":"Pathological response graded by Mandard scoring system and recorded by pathologist in medical file."}
• {"endpoint_text":"- Toxicity related to induction chemotherapy, graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Toxicity related to induction chemotherapy will be scored from day one of the first cycle until one month after the last administration of induction chemotherapy and is registered in the patient’s medical file by the treating oncologist. All CTCAE grade ≥ 2 and haematological CTCAE ≥ 3 AEs are registered.","definition_or_measurement_approach":"Toxicity graded per NCI CTCAE v5.0 from day 1 of first cycle until one month after last induction chemo; CTCAE grade ≥2 and hematological CTCAE ≥3 AEs recorded."}
• {"endpoint_text":"- Compliance related to induction chemotherapy. Information on compliance to treatment is registered by the treating oncologist in the patient's medical file.","definition_or_measurement_approach":"Compliance recorded by treating oncologist in patient's medical file for induction chemotherapy."}
• {"endpoint_text":"- Toxicity related to chemoradiotherapy according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Toxicity related to induction chemotherapy will be scored from day one of the first cycle until one month after the last administration of induction chemotherapy and is registered in the patient’s medical file by the treating oncologist. All CTCAE grade ≥ 2 and haematological CTCAE ≥ 3 AEs are registered.","definition_or_measurement_approach":"Toxicity related to chemoradiotherapy graded per NCI CTCAE v5.0 and recorded in medical file; CTCAE grade ≥2 and hematological CTCAE ≥3 recorded."}
• {"endpoint_text":"- Compliance related to chemoradiotherapy. Information on compliance to treatment is registered by the treating oncologist in the patient's medical file.","definition_or_measurement_approach":"Compliance recorded by treating oncologist in patient's medical file for chemoradiotherapy."}
• {"endpoint_text":"- Dose reductions during induction chemotherapy are registered by the treating oncologist. The treating oncologist will record the cycle in which the dose reduction takes place and the agent for which the dose is reduced. When a dose reduction is required, the reason for dose reduction will be recorded in the patient's medical file.","definition_or_measurement_approach":"Treating oncologist records cycle and agent for any dose reduction during induction chemo and documents reason in medical file."}
• {"endpoint_text":"- Dose reductions during chemoradiotherapy. The treating oncologist will record a dose reduction regarding capecitabine or Teysuno. The radiation oncologist will record a dose reduction regarding radiotherapy. When dose reduction is required, the reason for dose reduction will be recorded in the patient's medical file.","definition_or_measurement_approach":"Dose reductions recorded by treating oncologist (capecitabine/Teysuno) and radiation oncologist (radiotherapy); reasons documented in medical file."}
• {"endpoint_text":"- Completion rate of induction chemotherapy: this is calculated as a percentage from the total number of patients per group.","definition_or_measurement_approach":"Completion rate calculated as percentage of total patients per group."}
• {"endpoint_text":"- Completion rate of chemoradiothearpy: this is calculated as a percentage from the total number of patients per group.","definition_or_measurement_approach":"Completion rate calculated as percentage of total patients per group."}
• {"endpoint_text":"- Surgical characteristics: data on the surgical procedure are registered in the surgical report in the patient’s medical file by the operating surgeon. Data on intraoperative radiotherapy, if administered, are registered in the patient’s medical file by the radiation oncologist.","definition_or_measurement_approach":"Surgical procedure data recorded in surgical report by operating surgeon; intraoperative radiotherapy data recorded by radiation oncologist in medical file."}
• {"endpoint_text":"- Post-operative complications: data on postoperative complications, graded according to the Clavien-Dindo grading system, are registered in the patient’s medical file by the treating physician up to 3 months after surgery.","definition_or_measurement_approach":"Post-operative complications graded by Clavien-Dindo and recorded up to 3 months after surgery in medical file by treating physician."}
• {"endpoint_text":"- Quality of life questionnaires at baseline, after ICT, after CRT, 3 months, 12 months and 24 months post operatively or after entering a W&W approach. Validated quality of life questionnaires are used: QLQ-C30, QLQ-CR29, EQ-5D-5L, QLQ-CIPN-20","definition_or_measurement_approach":"QoL assessed using validated questionnaires (QLQ-C30, QLQ-CR29, EQ-5D-5L, QLQ-CIPN-20) at specified timepoints and recorded."}
• {"endpoint_text":"- Work productivity questionnaires: WPAI-GH questionnaire at baseline, after ICT and after CRT.","definition_or_measurement_approach":"Work productivity measured using WPAI-GH at baseline, after induction chemotherapy, and after chemoradiotherapy."}
• {"endpoint_text":"- Cost-effectiveness: the EQ-5D-5L questionnaire is used at baseline, and 12 months post-operatively.","definition_or_measurement_approach":"Cost-effectiveness assessed using EQ-5D-5L at baseline and 12 months post-operatively."}

Netherlands

Earliest CTIS Part Ii Submission Date

23-01-2026

Latest Decision Or Authorization Date

04-02-2026

Processing Time Days

12

Number Of Sites

11

Number Of Participants

394

Primary sponsor

Full Name

Catharina Ziekenhuis Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands