Neoadjuvant FOLFOX 4 versus FOLFOX 4 with Cetuximab versus immediate surgery for high-risk stage II and III colon cancers: a multicentre randomised controlled phase II trial – the PRODIGE 22 - ECKINOXE trial

BMC Cancer

Study Protocol

Julien Taieb¹  Iradj Sobhani²  Marie-Luce Auriault³  Karen Leroy³  Armelle Bardier⁴  Alain Luciani⁵  Isabelle Brindel⁶  Mehdi Karoui⁷  Franck Bonnetain⁸  Geneviève Monges⁹  Anne Rullier^1,10  Antony Sarran^1,11  Hervé Trillaud^1,12  Jean François Seitz^1,13  Karine Le Malicot^1,13  Marie Moreau^1,13 

[1] Assistance Publique-Hôpitaux de Paris, Department of Digestive Oncology, European Georges Pompidou – Paris Descartes University, Paris, France;FFCD (Fédération Francophone de Cancérologie Digestive), Dijon, France;Assistance Publique-Hôpitaux de Paris, Department of Gastroenterology, Henri Mondor University Hospital, Créteil, France;Assistance Publique-Hôpitaux de Paris, Department of Pathology, Henri Mondor University Hospital, Créteil, France;Assistance Publique-Hôpitaux de Paris, Department of Pathology, Pitié-Salpêtrière University Hospital, Paris, France;Assistance Publique-Hôpitaux de Paris, Department of Radiology, Henri Mondor University Hospital, Paris XII university, Créteil, France;Assistance Publique-Hôpitaux de Paris, Département de la Recherche Clinique et du Développement (DRCD), Paris, France;Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Department of Digestive and Hepato-Pancreato-Biliary Surgery, University Institute of Cancerology (Paris VI), Pierre & Marie Curie University (Paris VI), 47-83 Boulevard de l’Hôpital, 75013, Paris, France;FFCD (Fédération Francophone de Cancérologie Digestive), Dijon, France;Department of Medical Oncology and public health, Centre Hospitalier Régional Universitaire Hôpital Jean Minjoz, Besançon, France;Department of Pathology, Institut Paoli Calmettes, Marseille, France;Department of Pathology, Pellegrin University Hospital, Bordeaux, France;Department of Radiology, Institut Paoli Calmettes, Marseille, France;Department of Radiology, St André University Hospital, Bordeaux, France;FFCD (Fédération Francophone de Cancérologie Digestive), Dijon, France;

关键词: Colon cancer;    Locally advanced disease;    Neoadjuvant chemotherapy;    FOLFOX;    Cetuximab;    Randomized phase II trial;   

DOI  :  10.1186/s12885-015-1507-3

 received in 2014-10-19, accepted in 2015-06-19,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundIn patients with high risk stage II and stage III colon cancer (CC), curative surgery followed by adjuvant FOLFOX-4 chemotherapy has become the standard of care. However, for 20 to 30 % of these patients, the current curative treatment strategy of surgical excision followed by adjuvant chemotherapy fails either to clear locoregional spread or to eradicate distant micrometastases, leading to disease recurrence. Preoperative chemotherapy is an attractive concept for these CCs and has the potential to impact upon both of these causes of failure. Optimum systemic therapy at the earliest possible opportunity may be more effective at eradicating distant metastases than the same treatment given after the delay and immunological stress of surgery. Added to this, shrinking the primary tumor before surgery may reduce the risk of incomplete surgical excision, and the risk of tumor cell shedding during surgery.Methods/DesignPRODIGE 22 - ECKINOXE is a multicenter randomized phase II trial designed to evaluate efficacy and feasibility of two chemotherapy regimens (FOLFOX-4 alone and FOLFOX-4 + Cetuximab) in a peri-operative strategy in patients with bulky CCs. Patients with CC deemed as high risk T3, T4 and/or N2 on initial abdominopelvic CT scan are randomized to either colectomy and adjuvant chemotherapy (control arm), or 4 cycles of neoadjuvant chemotherapy with FOLFOX-4 (for RAS mutated patients). In RAS wild-type patients a third arm testing FOLFOX+ cetuximab has been added prior to colectomy. Patients in the neoadjuvant chemotherapy arms will receive postoperative treatment for 4 months (8 cycles) to complete their therapeutic schedule. The primary endpoint of the study is the histological Tumor Regression Grade (TRG) as defined by Ryan. The secondary endpoints are: treatment strategy safety (toxicity, primary tumor related complications under chemotherapy, peri-operative morbidity), disease-free and recurrence free survivals at 3 years, quality of life, carcinologic quality and completeness of the surgery, initial radiological staging and radiological response to neoadjuvant chemotherapy, and the correlation between histopathological and radiological response. Taking into account a 50 % prevalence of CC without RAS mutation, accrual of 165 patients is needed for this Phase II trial.Trial RegistrationNCT01675999 (ClinicalTrials.gov)

【 授权许可】

CC BY   
© Karoui et al. 2015