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Open Access Study protocol

Phase II/III multicentre randomised controlled trial evaluating a strategy of primary surgery and adjuvant chemotherapy versus peri-operative chemotherapy for resectable gastric signet ring cell adenocarcinomas – PRODIGE 19 – FFCD1103 – ADCI002

Guillaume Piessen123*, Mathieu Messager123, Karine Le Malicot4, William B Robb12, Frédéric Di Fiore5, Marie Guilbert12, Marie Moreau4, Véronique Christophe6, Antoine Adenis7 and Christophe Mariette123

Author Affiliations

1 Department of Digestive and Oncological Surgery, University Hospital of Lille, F-59037 Lille, France

2 University Lille Nord de France, F-59037 Lille, France

3 Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 Mucins, Epithelial Differentiation and Carcinogenesis, rue Polonovski, 59045 Lille Cedex, France

4 Fédération Francophone de Cancérologie Digestive, Medical University, 7 Bd Jeanne d'Arc, BP 87900 F-21079 Dijon cedex, France

5 Department of Gastroenterology, Digestive Oncology Unit, Rouen University Hospital, 1 rue de Germont, F-76031 Rouen Cedex, France

6 University Lille Nord de France - Université de Lille-III, URECA EA 1059, BP 60149 F-59653 Villeneuve-d'Ascq Cedex, France

7 Gastrointestinal Oncology Department, CLCC Oscar Lambret Comprehensive Cancer Center, 3 rue Combemale, F-59020 Lille cedex, France

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BMC Cancer 2013, 13:281  doi:10.1186/1471-2407-13-281

Published: 10 June 2013

Abstract

Background

A dramatic increase in the incidence of the diffuse form of gastric adenocarcinomas and particularly signet ring cell carcinomas has been observed in Western countries. Evidence is accruing that signet ring cell carcinomas may have inherent chemo resistance leaving many clinicians unsure of the benefits of delaying surgery to pursue a neoadjuvant approach.

Methods/design

PRODIGE-19-FFCD1103-ADCI002 is a prospective multicentre controlled randomised phase II/III trial comparing current standard of care of perioperative chemotherapy (2x3 cycles of Epirubicin, cisplatin, 5-fluorouracil) with a strategy of primary surgery followed by adjuvant chemotherapy (6 cycles of Epirubicin, cisplatin, 5-fluorouracil) in patients with a stage IB-III gastric signet ring cell tumour. The principal objective of the phase II study (84 patients) is to determine if the experimental arm (primary surgery followed by adjuvant chemotherapy) has sufficient interest in terms of percentage of living patients at 24 months to be evaluated in a phase III trial. If 7 or less patients in the experimental arm are alive at 24 months, phase III will not be initiated. The primary objective of phase III (230 additional patients) is to demonstrate superiority of the experimental arm in terms of overall survival. Secondary endpoints include overall survival at 36 months, disease free survival at 24 and 36 months, R0 resection rates, treatment tolerance, postoperative mortality and morbidity evaluated by Clavien-Dindo severity index, the prognostic impact of positive peritoneal cytology and the assessment of quality of life. An ancillary study will assess the emotional and cognitive impact of surgery and perioperative chemotherapy for both the patient and their partner.

Discussion

As inherent chemo resistance of signet ring cell tumours and delay in definitive surgery may favour tumour progression we hypothesise that a policy of primary surgery followed by adjuvant chemotherapy will improve overall survival compared to a standard perioperative chemotherapeutic strategy. This randomised phase II/III trial is the first dedicated to this histological subtype. Whilst the development of new biomarkers and targeted therapies are awaited, the results of this trial should further help in devising individualised protocols of patient care in a tumour group whose diversity increasingly demands assessment of alternative strategies.

Trial registration

ClinicalTrials.gov, NCT01717924

Keywords:
Signet ring cells; Gastric adenocarcinoma; Surgery; Perioperative chemotherapy; Randomized study; Emotion; Couple