The RENAISSANCE (AIO-FLOT5) trial: effect of chemotherapy alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction - a phase III trial of the German AIO/CAO-V/CAOGI

Abstract

Background: Historical data indicate that surgical resection may benefit select patients with metastatic gastric and gastroesophageal junction cancer. However, randomized clinical trials are lacking. The current RENAISSANCE trial addresses the potential benefits of surgical intervention in gastric and gastroesophageal junction cancer with limited metastases.

Methods: This is a prospective, multicenter, randomized, investigator-initiated phase III trial. Previously untreated patients with limited metastatic stage (retroperitoneal lymph node metastases only or a maximum of one incurable organ site that is potentially resectable or locally controllable with or without retroperitoneal lymph nodes) receive 4 cycles of FLOT chemotherapy alone or with trastuzumab if Her2+. Patients without disease progression after 4 cycles are randomized 1:1 to receive additional chemotherapy cycles or surgical resection of primary and metastases followed by subsequent chemotherapy. 271 patients are to be allocated to the trial, of which at least 176 patients will proceed to randomization. The primary endpoint is overall survival; main secondary endpoints are quality of life assessed by EORTC-QLQ-C30 questionnaire, progression free survival and surgical morbidity and mortality. Recruitment has already started; currently (Feb 2017) 22 patients have been enrolled.

Discussion: If the RENAISSANCE concept proves to be effective, this could potentially lead to a new standard of therapy. On the contrary, if the outcome is negative, patients with gastric or GEJ cancer and metastases will no longer be considered candidates for surgical intervention.

Trial registration: The article reports of a health care intervention on human participants and is registered on October 12, 2015 under ClinicalTrials.gov Identifier: NCT02578368 ; EudraCT: 2014-002665-30.

Keywords: FLOT- regimen; Gastrectomy; Limited-metastatic disease; Localized peritoneal carcinomatosis; Metastatic gastric cancer; Metastatic gastroesophageal junction cancer; Oligometastatic cancer; Perioperative chemotherapy; Quality of life; Resection of metastases.

Conflict of interest statement

Authors’ information

AB is the study coordinator, obtained the grant and TG is responsible for the present paper.

Ethics approval and consent to participate

The study protocol was approved by the responsible lead ethics committee of the Landesärtzekammer Hessen, Im Vogelsgesang 3; 60,488 Frankfurt am Main, Germany, responsible for the Krankenhaus Nordwest Frankfurt- UCT (University Cancer Center)on the 11th of January 2016 under the identification number FF123/2015. A trial amendment was approved by the responsible lead ethics committee on 13ten of May 2016, Version 2.0. The study has been registered on the ClinicalTrial.gov website under the identification number NCT02578368. The RENAISSANCE study complies with the Declaration of Helsinki rules, the principles of Good Clinical Practice guidelines and the Data Protection Act. The trial will also be carried out in compliance to local legal and regulatory requirements. For each patient to be enrolled into the study, obtaining written informed consent prior to inclusion into the study is essential.

Consent for publication

“Not applicable”.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

RENAISSANCE study flow chart (schematic)