Induction chemotherapy followed by chemoradiotherapy <i>versus</i> chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: study protocol of a multicentre, open-label, parallel-arms, randomized controlled study (PelvEx II)
PelvEx Collaborative, E L K Voogt, Stefi Nordkamp, Arend G. J. Aalbers, Tineke E. Buffart, G.J. Creemers, Corrie A.M. Marijnen, Cornelis Verhoef, Klaas Havenga, Fabian A. Holman, Miranda Kusters, Andreas Marinelli, Jarno Melenhorst, Nora Abdul Aziz, Nuno Abecasis, Mirna Abraham‐Nordling, Takashi Akiyoshi, W Alberda, M. Albert, Mihailo Andric, Eva Angenete, A Antoniou, Roland N. Auer, Kirk K. S. Austin, Omer Aziz, Rachel Baker, M Bali, Gediminas Baseckas, Brendan Bebington, Michael Bedford, Brian K. Bednarski, Geerard L. Beets, R.G.H. Beets-Tan, Maaike Berbée, Jurriën M. ten Berg, P L Berg, J Beynon, Sebastiano Biondo, Johanne G. Bloemen, K Boyle, Liliana Bordeianou, A B Bremers, Markus Brunner, P. Buchwald, Ai‐Tram N. Bui, A W Burgess, David Burling, Ethan Burns, Nicholas Campain, Sara Carvalhal, Luis M. Castro, Antonio Caycedo‐Marulanda, Heleen M. Ceha, Karen K. L. Chan, George J. Chang, Ming Chu Chang, Min Hoe Chew, Amanda Kay-Lyn Chok, Peter Chong, Helen Christensen, H.W. Clouston, Mary Codd, Danielle Collins, A J Colquhoun, Alison Corr, Maurizio Coscia, Maurizio Cosimelli, Peter Coyne, A. Stijn L. P. Crobach, Rogier M. P. H. Crolla, Roland S. Croner, L Damjanovic, I. R. Daniels, Matthew L. Davies, Robert J.O. Davies, Conor P. Delaney, Matthew Roos, Johannes H. W. de Wilt, M.D. den Hartogh, Quentin Denost, Pieter Deseyne, C Deutsch, R de Vos tot Nederveen Cappel, M de Vries, Margriet Dieters, David Dietz, S Domingo, Michail Doukas, Eric J. Dozois, M. J. Duff, Tim Eglinton, J M Enrique-Navascues, Eloy Espín, M. D. Evans, Brynhildur Eyjólfsdóttir, Matthew R. Fahy, Nicola Fearnhead, Shirin S. Feshtali, Kjersti Flatmark, Fergal J. Fleming
Abstract
BACKGROUND: A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC. METHODS: This multicentre, international, open-label, phase III, parallel-arms study will enrol 364 patients with resectable LRRC after previous partial or total mesorectal resection without synchronous distant metastases or recent chemo- and/or radiotherapy treatment. Patients will be randomized to receive either induction chemotherapy (three 3-week cycles of CAPOX (capecitabine, oxaliplatin), four 2-week cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) or FOLFORI (5-fluorouracil, leucovorin, irinotecan)) followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm). Tumours will be restaged using MRI and, in the experimental arm, a further cycle of CAPOX or two cycles of FOLFOX/FOLFIRI will be administered before chemoradiotherapy in case of stable or responsive disease. The radiotherapy dose will be 25 × 2.0 Gy or 28 × 1.8 Gy in radiotherapy-naive patients, and 15 × 2.0 Gy in previously irradiated patients. The concomitant chemotherapy agent will be capecitabine administered twice daily at a dose of 825 mg/m2 on radiotherapy days. The primary endpoint of the study is the R0 resection rate. Secondary endpoints are long-term oncological outcomes, radiological and pathological response, toxicity, postoperative complications, costs, and quality of life. DISCUSSION: This trial protocol describes the PelvEx II study. PelvEx II, designed as a multicentre, open-label, phase III, parallel-arms study, is the first randomized study to compare induction chemotherapy followed by neoadjuvant chemo(re)irradiation and surgery with neoadjuvant chemo(re)irradiation and surgery alone in patients with locally recurrent rectal cancer, with the aim of improving the number of R0 resections.