[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100629299":3},{"organization":4,"armGroups":7,"interventions":28,"overallOfficials":89,"centralContacts":93,"locations":100,"responsibleParty":117,"collaborators":121,"id":124,"slug":125,"hasResults":126,"nctId":127,"briefTitle":128,"officialTitle":129,"acronym":130,"eligibilityCriteria":131,"healthyVolunteers":126,"sex":132,"minAge":133,"maxAge":98,"enrollmentInfo":134,"targetDuration":98,"studyType":137,"phases":138,"briefSummary":140,"conditions":141,"keywords":143,"overallStatus":151,"whyStopped":98,"lastUpdateSubmitDate":152,"lastUpdatePostDateStruct":153,"startDateStruct":156,"completionDateStruct":158,"leadSponsor":160,"locationsCount":161},{"fullName":5,"class":6},"Catharina Ziekenhuis Eindhoven","OTHER",[8,17,24],{"label":9,"type":10,"description":11,"interventionNames":12},"Triplet induction chemotherapy (FOLFOXIRI)","EXPERIMENTAL","Triplet induction chemotherapy (FOLFOXIRI) followed by chemoradiotherapy and surgery or a watch-and-wait approach.",[13,14,15,16],"Drug: FOLFOXIRI","Radiation: Chemoradiotherapy","Procedure: Total mesorectal excision (+\u002F- IORT)","Diagnostic Test: Watch-and-wait approach",{"label":18,"type":19,"description":20,"interventionNames":21},"Doublet induction chemotherapy (CAPOX\u002FFOLFOX)","ACTIVE_COMPARATOR","Doublet induction chemotherapy (FOLFOXIRI) followed by chemoradiotherapy and surgery or a watch-and-wait approach.",[22,23,14,15,16],"Drug: CAPOX","Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)",{"label":25,"type":6,"description":26,"interventionNames":27},"Registration arm: chemoradiotherapy alone","A registration arm in which patients who do not want to participate in the randomised study and who will receive chemoradiation alone as neoadjuvant treatment - followed by surgery or a Watch-and-Wait approach in accordance with standard-of-care.",[14,15,16],[29,43,50,55,63,76],{"type":30,"name":31,"description":32,"armGroupLabels":33,"otherNames":34},"DRUG","FOLFOXIRI","ICT consists of four or six two-weekly cycles of FOLFOXIRI. The dosages, dosage modification, and methods and schedule of administration of FOLFOXIRI follows the established treatment protocols and standard of care as prescribed in the Dutch Guidelines. It is administered as follows:\n\n* Day 1: irinotecan 165 mg\u002Fm2 body-surface area (BSA) intravenously (IV), followed by oxaliplatin 85mg\u002Fm2 BSA IV in combination with leucovorin 400mg\u002Fm2 BSA, followed by:\n* Day 1-2: 3200 mg\u002Fm2 BSA of continuous 5-fluorouracil IV\n* Day 3-14: rest days.",[9],[35,36,37,38,39,40,41,42],"Triplet","Induction chemotherapy","Total neoadjuvant therapy","5-FU","5-fluorouracil","Irinotecan","Leucovorin","Oxaliplatin",{"type":30,"name":44,"description":45,"armGroupLabels":46,"otherNames":47},"CAPOX","The dosages, dosage modification, and methods and schedule of administration of CAPOX follows the established treatment protocols and standard of care as prescribed in the Dutch Guidelines. CAPOX is administered as follows:\n\n* Day 1: Oxaliplatin 130 mg\u002Fm2 body-surface area \\[BSA\\], intravenously \\[IV\\].\n* Day 1-14: Capecitabine 1000 mg\u002Fm2 BSA, orally, twice daily.\n* Day 15-21: Rest days.\n\nThis regimen is initially administered for three cycles. In case of responsive or stable disease, a 4th cycle of CAPOX will be administered. In case of unacceptable toxicity (physician's discretion) to oxaliplatin, CAPOX may be continued as FOLFOX.",[18],[48,36,37,49,42],"Doublet","Capecitabine",{"type":30,"name":51,"description":52,"armGroupLabels":53,"otherNames":54},"FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)","FOLFOX is a combination chemotherapy regimen, consisting of:\n\n* 5-fluorouracil (chemical name: L01BC02; trade name: 5-Fluorouracil; formulation: concentrate for solution for injection)\n* Oxaliplatin (chemical name: L01XA03; trade name: Oxaliplatin Accord; formulation: concentrate for solution for injection)\n\nFOLFOX is a well-established chemotherapy combination regimen for colorectal cancer, and is authorised for its intended use in this study. All FOLFOX component agents will be sourced from commercially available hospital stock and prepared according to standard protocols at participating centres.",[18],[48,36,38,39,41,42],{"type":56,"name":57,"description":58,"armGroupLabels":59,"otherNames":60},"RADIATION","Chemoradiotherapy","In accordance with established standard-of-care protocols, chemoradiotherapy will commence 3-6 weeks after the completion of ICT, following restaging imaging and MDT review. The standard chemoradiotherapy regimen consists of external beam radiotherapy 50Gy in fractions of 2 Gy or 50.4 Gy in fractions of 1.8Gy combined with concomitant capecitabine, administered in accordance with Dutch Guidelines:\n\n* Dosage: 825 mg\u002Fm² Body Surface Area (BSA), twice daily\n* Route of administration: orally\n* Schedule: administered on all radiotherapy days\n* Treatment duration: 25 days\n\nIn the case of cardiotoxicity or severe hand-foot syndrome due to capecitabine, treatment may be switched to Teysuno, in accordance with the Dutch guideline. The recommended dose of Teysuno in combination with oxaliplatin is 25 mg\u002Fm² body surface area, administered twice daily.",[18,25,9],[49,61,62],"Radiation","Teysuno",{"type":64,"name":65,"description":66,"armGroupLabels":67,"otherNames":68},"PROCEDURE","Total mesorectal excision (+\u002F- IORT)","In patients with an incomplete response and resectable disease after first restaging, surgery is performed according to standard of care by a surgical oncologist with experience in rectal cancer surgery within 10-14 weeks after completion of chemoradiotherapy. The type and extent of the surgery is left to the discretion of the operating surgeon. In case of need for reconstructive surgery, the required specialist will be consulted and will attend the surgical procedure. The addition of IORT will be left to the discretion of the surgeon.",[18,25,9],[69,70,71,72,73,74,75,61],"TME","Low Anterior Resection","LAR","Abdominoperineal Rectal Amputation","APR","Intra-operative Radiotherapy","IORT",{"type":77,"name":78,"description":79,"armGroupLabels":80,"otherNames":81},"DIAGNOSTIC_TEST","Watch-and-wait approach","When a cCR is achieved after neoadjuvant therapy, patients may opt for a W\\&W approach. A cCR is confirmed by imaging, endoscopy and digital rectal examination. Patients will receive a close surveillance follow up scheme according to the standard of care and local guidelines (51-54). Conduct follow-up every 3 months in the first year, every 6 months in the second year, and every 6 to 12 months in years 3 to 5, consisting of MRI and endoscopic evaluation. If any changes to the scar are detected during follow-up, a biopsy should be performed.",[18,25,9],[82,83,84,85,86,87,88],"W&W","Endoscopy","Magnetic Resonance Imaging","MRI","Colonoscopy","Computer Tomography","CT",[90],{"name":91,"affiliation":5,"role":92},"Jacobus WA Burger, Prof. dr.","PRINCIPAL_INVESTIGATOR",[94],{"name":95,"role":96,"phone":97,"phoneExt":98,"email":99},"Maaike M Borg, Drs.","CONTACT","+31 40 239 6641",null,"mend-it@catharinaziekenhuis.nl",[101],{"facility":102,"status":98,"city":103,"state":104,"zip":105,"country":106,"countryCode":107,"cosmosGeoPoint":108,"geoPoint":113,"contacts":114},"Catharina Hospital Eindhoven","Eindhoven","North Brabant","5623 EJ","Netherlands","NL",{"type":109,"coordinates":110},"Point",[111,112],5.47778,51.44083,{"lat":112,"lon":111},[115,116],{"name":95,"role":96,"phone":97,"phoneExt":98,"email":99},{"name":91,"role":92,"phone":98,"phoneExt":98,"email":98},{"type":118,"investigatorFullName":119,"investigatorTitle":120,"investigatorAffiliation":5,"oldNameTitle":98,"oldOrganization":98},"SPONSOR_INVESTIGATOR","J. W. A. Burger","Prof. dr.",[122],{"name":123,"class":6},"ZonMw: The Netherlands Organisation for Health Research and Development","100629299","phase-3-neoadjuvant-folfoxiri-and-chemoradiotherapy-versus-neoadjuvant-capoxfolfox-and-chemoradiotherapy-followed-by-surgery-or-a-watch-and-wait-approach-in-high-risk-locally-advanced-rectal-cancer-100629299",false,"NCT07472868","Neoadjuvant FOLFOXIRI and Chemoradiotherapy Versus Neoadjuvant CAPOX\u002FFOLFOX and Chemoradiotherapy Followed by Surgery or a Watch-and-Wait Approach in High Risk Locally Advanced Rectal Cancer","MEND-IT II: Neoadjuvant FOLFOXIRI and Chemoradiotherapy Versus Neoadjuvant CAPOX\u002FFOLFOX and Chemoradiotherapy, Followed by Surgery or a Watch-and-Wait Approach in High Risk Locally Advanced Rectal Cancer.","MEND-IT II","Inclusion Criteria:\n\n* 18 years or older\n* WHO performance score 0-1.\n* Fit for (modified dose) triple chemotherapy (FOLFOXIRI)\n* Histopathological confirmed rectal cancer. (Lower border of the tumour located on or below the sigmoidal take-off as established on MRI of the pelvis.)\n* Confirmed high-risk locally advanced rectal cancer, at high risk of treatment failure, meeting one of the following imaging-based criteria:\n\n  * cT4b-tumour or evident tumour invasion of the MRF: distance to MRF 0 mm AND thickening of the MRF over a length of approximately 5 mm (MRF ≤ 1 mm is not considered sufficient).\n  * The presence of grade 4 extramural venous invasion (mrEMVI)\n  * The presence of tumour deposits (TD)\n  * The presence of bilateral extramesorectal lymph nodes with a short-axis size ≥ 7mm (LLN) or extensive LLN involving pelvic side wall structures, at high risk of an incomplete resection.\n* Resectable disease as determined on magnetic resonance imaging (MRI) or deemed resectable disease after neoadjuvant treatment. (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.\n\nExclusion Criteria:\n\n* 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\u002For radiation oncologist.\n* Any contraindication to undergo surgery, as determined by the surgeon and\u002For anaesthesiologist.\n* Concurrent malignancies that interfere with the planned study treatment or the prognosis of the resected tumour.\n* Microsatellite instability (MSI).","ALL","18 Years",{"count":135,"type":136},394,"ESTIMATED","INTERVENTIONAL",[139],"PHASE3","The aim of this clinical trial is to compare triplet induction therapy (FOLFOXIRI) with doublet induction therapy (CAPOX\u002FFOLFOX), followed by chemoradiotherapy and either surgery or a watch-and-wait approach, in patients with high-risk locally advanced rectal cancer. The primary questions it seeks to address are whether triplet induction therapy results in higher complete response rates, improved quality of life, and better long-term oncological outcomes compared to doublet induction therapy, despite the anticipated increased risk of toxicity.",[142],"Locally Advanced Rectal Carcinoma",[37,36,144,145,146,147,148,149,150],"Locally advanced rectal carcinoma","Complete response","Toxicity","Quality of life","Organ sparing therapies","De-escalation","Survival","NOT_YET_RECRUITING","2026-03-10",{"date":154,"type":155},"2026-03-16","ACTUAL",{"date":157,"type":136},"2026-03-03",{"date":159,"type":136},"2034-03-02",{"name":119,"class":6},1]