1. Neoadjuvant FOLFOXIRI prior to chemoradiotherapy for high-risk ('ugly') locally advanced rectal cancer: study protocol of a single-arm, multicentre, open-label, phase II trial (MEND-IT)
- Author
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van den Berg, K., Schaap, D. P., Voogt, E. L. K., Buffart, T. E., Verheul, H. M. W., de Groot, J. W. B., Verhoef, C., Melenhorst, J., Roodhart, J. M. L., de Wilt, J. H. W., van Westreenen, H. L., Aalbers, A. G. J., van 't Veer, M., Marijnen, C. A. M., Vincent, J., Simkens, L. H. J., Peters, N. A. J. B., Berbée, M., Werter, I. M., Snaebjornsson, P., Peulen, H. M. U., van Lijnschoten, I. G., Roef, M. J., Nieuwenhuijzen, G. A. P., Bloemen, J. G., Willems, J. M. W. E., Creemers, G. J. M., Nederend, J., Rutten, H. J. T., Burger, J. W. A., Surgery, MUMC+: MA Heelkunde (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Radiotherapie, MUMC+: MA Radiotherapie OC (9), RS: GROW - R2 - Basic and Translational Cancer Biology, Internal medicine, Radiation Oncology, Eindhoven MedTech Innovation Center, Cardiovascular Biomechanics, and Rehabilitation Medicine
- Subjects
Neoadjuvant treatment ,Cancer Research ,Organoplatinum Compounds ,Leucovorin ,SDG 3 – Goede gezondheid en welzijn ,Fluorouracil/therapeutic use ,Neoadjuvant chemotherapy ,Chemoradiotherapy/methods ,Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] ,All institutes and research themes of the Radboud University Medical Center ,Clinical Trials, Phase II as Topic ,SDG 3 - Good Health and Well-being ,Neoplasms ,Antineoplastic Combined Chemotherapy Protocols ,Genetics ,Humans ,Multicenter Studies as Topic ,Clinical Trials ,Locally advanced rectal cancer ,Neoplasm Staging ,Neoplasms, Second Primary/pathology ,Pathological complete response ,Rectal Neoplasms ,Antineoplastic Combined Chemotherapy Protocols/adverse effects ,Neoadjuvant Therapy/methods ,Phase II as Topic ,Neoplasms, Second Primary ,Chemoradiotherapy ,Complete response ,Clinical complete response ,Neoadjuvant Therapy ,Second Primary/pathology ,Treatment Outcome ,Oncology ,Induction chemotherapy ,Quality of Life ,Camptothecin/analogs & derivatives ,Camptothecin ,Fluorouracil ,Rectal Neoplasms/pathology - Abstract
Background The presence of mesorectal fascia (MRF) invasion, grade 4 extramural venous invasion (EMVI), tumour deposits (TD) or extensive or bilateral extramesorectal (lateral) lymph nodes (LLN) on MRI has been suggested to identify patients with indisputable, extensive locally advanced rectal cancer (LARC), at high risk of treatment failure. The aim of this study is to evaluate whether or not intensified chemotherapy prior to neoadjuvant chemoradiotherapy improves the complete response (CR) rate in these patients. Methods This multicentre, single-arm, open-label, phase II trial will include 128 patients with non-metastatic high-risk LARC (hr-LARC), fit for triplet chemotherapy. To ensure a study population with indisputable, unfavourable prognostic characteristics, hr-LARC is defined as LARC with on baseline MRI at least one of the following characteristics; MRF invasion, EMVI grade 4, enlarged bilateral or extensive LLN at high risk of an incomplete resection, or TD. Exclusion criteria are the presence of a homozygous DPD deficiency, distant metastases, any chemotherapy within the past 6 months, previous radiotherapy within the pelvic area precluding standard chemoradiotherapy, and any contraindication for the planned treatment. All patients will be planned for six two-weekly cycles of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) prior to chemoradiotherapy (25 × 2 Gy or 28 × 1.8 Gy with concomitant capecitabine). A resection will be performed following radiological confirmation of resectable disease after the completion of chemoradiotherapy. A watch and wait strategy is allowed in case of a clinical complete response. The primary endpoint is the CR rate, described as a pathological CR or a sustained clinical CR one year after chemoradiotherapy. The main secondary objectives are long-term oncological outcomes, radiological and pathological response, the number of resections with clear margins, treatment-related toxicity, perioperative complications, health-related costs, and quality of life. Discussion This trial protocol describes the MEND-IT study. The MEND-IT study aims to evaluate the CR rate after intensified chemotherapy prior to concomitant chemoradiotherapy in a homogeneous group of patients with locally advanced rectal cancer and indisputably unfavourable characteristics, defined as hr-LARC, in order to improve their prognosis. Trial registration Clinicaltrials.gov: NCT04838496, registered on 02–04-2021 Netherlands Trial Register: NL9790. Protocol version Version 3 dd 11–4-2022.
- Published
- 2022
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