Bevacizumab and Combination Chemotherapy in rectal cancer Until Surgery (BACCHUS): a phase II, multicentre, open-label, randomised study of neoadjuvant chemotherapy alone in patients with high-risk cancer of the rectum

BMC Cancer

Study Protocol

N. Hava¹  S. Beare¹  A. Lopes¹  M. Jitlal¹  H. Wasan²  I. Chau³  Wai-Lup Wong⁴  B. Moran⁵  V. Goh⁶  P. Quirke⁷  N. West⁷  S. Bosompem⁸  L. Melcher⁹  A. Gaya^1,10  M. Hall^1,11  M. Harrison^1,11  R. Glynne-Jones^1,11  A. MacDonald^1,12  M. Osborne^1,13  J. Bridgewater^1,14 

[1] Cancer Research UK & University College London Cancer Trials Centre, London, UK;Department of Cancer Medicine, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK;Department of Medical Oncology, Royal Marsden Hospital, London & Surrey, UK;Department of Radiology, Paul Strickland Scanner Centre, Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, UK;Department of Surgery, Hampshire Hospitals Foundation Trust, Basingstoke, Hampshire, UK;Division of Imaging Sciences & Biomedical Engineering, Kings College London, London, Department of Radiology, Guy’s and St Thomas’ Hospitals NHS Foundation Trust, SE1 7EH, London, UK;Leeds Institute of Cancer and Pathology, School of Medicine, University of Leeds, Leeds, United Kingdom;Pharmacy, Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, UK;Radiotherapy Department, Beatson Oncology Centre, 1053 Great Western Rd, Glasgow G12 0YN, UK;Radiotherapy Department, Guys and St Thomas’s Hospital, Westminster Bridge Road, SE1 7EH, London, UK;Radiotherapy Department, Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, UK;Radiotherapy Department, North Middlesex Hospital, Sterling Way, London N18 1QX, UK;Radiotherapy Department, Royal Devon & Exeter Hospital, Barrack Rd, Exeter, Devon EX2 5DW, UK;University College, London Cancer Institute, 72 Huntley St., WC1E 6AA, London, UK;

关键词: FOLFOXIRI;    FOLFOX;    Bevacizumab;    Locally advanced rectal cancer;    Total mesorectal excision;    Resectable;    Metastatic disease;   

DOI  :  10.1186/s12885-015-1764-1

 received in 2014-06-30, accepted in 2015-10-10,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundIn locally advanced rectal cancer (LARC) preoperative chemoradiation (CRT) is the standard of care, but the risk of local recurrence is low with good quality total mesorectal excision (TME), although many still develop metastatic disease. Current challenges in treating rectal cancer include the development of effective organ-preserving approaches and the prevention of subsequent metastatic disease.Neoadjuvant systemic chemotherapy (NACT) alone may reduce local and systemic recurrences, and may be more effective than postoperative treatments which often have poor compliance. Investigation of intensified NACT is warranted to improve outcomes for patients with LARC. The objective is to evaluate feasibility and efficacy of a four-drug regimen containing bevacizumab prior to surgical resection.Methods/designThis is a multi-centre, randomized phase II trial. Eligible patients must have histologically confirmed LARC with distal part of the tumour 4–12 cm from anal verge, no metastases, and poor prognostic features on pelvic MRI. Sixty patients will be randomly assigned in a 1:1 ratio to receive folinic acid + flurourcil + oxaliplatin (FOLFOX) + bevacizumab (BVZ) or FOLFOX + irinotecan (FOLFOXIRI) + BVZ, given in 2 weekly cycles for up to 6 cycles prior to TME. Patients stop treatment if they fail to respond after 3 cycles (defined as ≥ 30 % decrease in Standardised Uptake Value (SUV) compared to baseline PET/CT).The primary endpoint is pathological complete response rate. Secondary endpoints include objective response rate, MRI tumour regression grade, involved circumferential resection margin rate, T and N stage downstaging, progression-free survival, disease-free survival, overall survival, local control, 1-year colostomy rate, acute toxicity, compliance to chemotherapy.DiscussionIn LARC, a neoadjuvant chemotherapy regimen - if feasible, effective and tolerable would be suitable for testing as the novel arm against the current standards of short course preoperative radiotherapy (SCPRT) and/or fluorouracil (5FU)-based CRT in a future randomised phase III trial.Trial registrationClinical trial identifier BACCHUS: NCT01650428

【 授权许可】

CC BY   
© Glynne-Jones et al. 2015