eprintid: 26184
rev_number: 13
eprint_status: archive
userid: 1589
dir: disk0/00/02/61/84
datestamp: 2019-05-21 11:07:26
lastmod: 2024-03-09 16:56:04
status_changed: 2019-05-21 11:07:26
type: article
metadata_visibility: show
creators_name: Meindl-Beinker, Nadja M.
creators_name: Betge, Johannes
creators_name: Gutting, Tobias
creators_name: Burgermeister, Elke
creators_name: Belle, Sebastian
creators_name: Zhan, Tianzuo
creators_name: Schulte, Nadine
creators_name: Maenz, Martin
creators_name: Ebert, Matthias P.
creators_name: Haertel, Nicolai
title: A multicenter open-label phase II trial to evaluate nivolumab and ipilimumab for 2nd line therapy in elderly patients with advanced esophageal squamous cell cancer (RAMONA)
subjects: ddc-610
divisions: i-62300
keywords: Esophageal squamous cell cancer, Elderly, Comprehensive geriatric assessment, Checkpoint inhibitors, Personalized medicine, Geriatric oncology
abstract: Background: Advanced esophageal squamous cell cancer (ESCC) is frequently diagnosed in elderly patients. The impact of 2nd line chemotherapy is poorly defined. Recent data demonstrated effectiveness of checkpoint inhibitors in different squamous cell carcinomas. Therefore, we assess combined nivolumab/ipilimumab as 2nd line therapy in elderly ESCC patients.

Methods: RAMONA is a multicenter open-label phase II trial. The primary objective is to demonstrate a significant survival benefit of nivolumab/ipilimumab in advanced ESCC compared to historical data of standard chemotherapy. Primary endpoint is therefore overall survival (OS). Major secondary objective is the evaluation of tolerability. Time to QoL deterioration will thus be determined as key secondary endpoint. Further secondary endpoints are tumor response, PFS and safety. We aim to recruit a total of n = 75 subjects that have to be > 65 years old. Eligibility is determined by the geriatric status (G8 screening and Deficit Accumulation Frailty Index (DAFI)). A safety assessment will be performed after a 3 cycle run-in phase of nivolumab (240 mg Q2W) to justify escalation for eligible patients to combined nivolumab (240 mg Q2W) and ipilimumab (1 mg/kg Q6W), while the other patients will remain on nivolumab only. RAMONA also includes translational research sub-studies to identify predictive biomarkers, including PD-1 and PD-L1 evaluation at different time points, establishment of organoid cultures and microbiome analyses for response prediction.

Discussion: The RAMONA trial aims to implement checkpoint inhibitors for elderly patients with advanced ESCC as second line therapy. Novel biomarkers for checkpoint-inhibitor response are analyzed in extensive translational sub-studies.

Trial registration: EudraCT Number 2017–002056-86; NCT03416244, 
registered: 31.1.2018.
date: 2019
publisher: BioMed Central ; Springer
id_scheme: DOI
ppn_swb: 1666510092
own_urn: urn:nbn:de:bsz:16-heidok-261845
language: eng
bibsort: MEINDLBEINAMULTICENT2019
full_text_status: public
publication: BMC Cancer
volume: 19
number: 231
place_of_pub: London ; Berlin, Heidelberg
pagerange: 1-8
issn: 1471-2407
citation:   Meindl-Beinker, Nadja M. ; Betge, Johannes ; Gutting, Tobias ; Burgermeister, Elke ; Belle, Sebastian ; Zhan, Tianzuo ; Schulte, Nadine ; Maenz, Martin ; Ebert, Matthias P. ; Haertel, Nicolai  (2019) A multicenter open-label phase II trial to evaluate nivolumab and ipilimumab for 2nd line therapy in elderly patients with advanced esophageal squamous cell cancer (RAMONA).  BMC Cancer, 19 (231).  pp. 1-8.  ISSN 1471-2407     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/26184/1/12885_2019_Article_5446.pdf