TY  - JOUR
A1  - Meindl-Beinker, Nadja M.
A1  - Betge, Johannes
A1  - Gutting, Tobias
A1  - Burgermeister, Elke
A1  - Belle, Sebastian
A1  - Zhan, Tianzuo
A1  - Schulte, Nadine
A1  - Maenz, Martin
A1  - Ebert, Matthias P.
A1  - Haertel, Nicolai
Y1  - 2019///
JF  - BMC Cancer
ID  - heidok26184
AV  - public
CY  - London ; Berlin, Heidelberg
TI  - 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)
KW  - Esophageal squamous cell cancer
KW  -  Elderly
KW  -  Comprehensive geriatric assessment
KW  -  Checkpoint inhibitors
KW  -  Personalized medicine
KW  -  Geriatric oncology
PB  - BioMed Central ; Springer
EP  - 8
SN  - 1471-2407
SP  - 1
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/26184/
N2  - 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.
VL  - 19
IS  - 231
ER  -