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)

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.

doi:https://doi.org/10.1186/s12885-022-09947-w

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)

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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)

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.

(2022) BMC Cancer, volume 22, issue 1

(Article)

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 ... read more 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.

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Keywords: Clinical complete response, Complete response, Induction chemotherapy, Locally advanced rectal cancer, Neoadjuvant chemotherapy, Neoadjuvant treatment, Pathological complete response, Rectal Neoplasms/pathology, Neoplasms, Second Primary/pathology, Humans, Organoplatinum Compounds, Treatment Outcome, Leucovorin, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Chemoradiotherapy/methods, Fluorouracil/therapeutic use, Multicenter Studies as Topic, Quality of Life, Neoadjuvant Therapy/methods, Neoplasm Staging, Camptothecin/analogs & derivatives, Clinical Trials, Phase II as Topic, Genetics, Oncology, Cancer Research, Journal Article

DOI: https://doi.org/10.1186/s12885-022-09947-w

ISSN: 1471-2407

Publisher: BioMed Central

Note: Funding Information: This study is part of the ‘highly specialized care and research programme (TZO programme)’, funded by the Netherlands Organisation for Health Research and Development (ZonMw). The research proposal was assessed on quality by external referees during the assessment procedure. ZonMW will not benefit financially from the results of this study. Publisher Copyright: © 2022, The Author(s).

(Peer reviewed)