RAP: A phase II trial with ramucirumab, avelumab, and paclitaxel as second line treatment in gastro-esophageal adenocarcinoma of the arbeitsgemeinschaft internistische onkologie (AIO)

Autor: Axel Hinke, Alexander Stein, Kirstin Breithaupt, Anica Högner, Salah-Eddin Al-Batran, Peter C. Thuss-Patience, Mario Lorenz
Rok vydání: 2019
Předmět:
Zdroj: Journal of Clinical Oncology. 37:TPS4148-TPS4148
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2019.37.15_suppl.tps4148
Popis: TPS4148 Background: Combination of ramucirumab and paclitaxel resembles the standard treatment option in second line therapy with improvement of response rate and overall survival (REGARD, RAINBOW). Response rates to PD-1/L1 blockade in gastro-esophageal cancer patients rank within 10–20%, whereby PD-1/L1 blockade is reported to impressively extend survival rates in responders. Trials investigating either the synergistic effect of anti-angiogenesis and anti-PD-L1 or chemotherapy combined with anti-PD-L1 are promising. Based on these data we hypothesize benefit from combining immunotherapy by checkpoint inhibition with VEGF-directed treatment and chemotherapy induced increase of immunogenicity of tumor cells. This study investigates the incorporation of PD-L1 blockade by avelumab in the second line setting by combination with the actual best second-line chemotherapy regimen in metastatic gastric cancer patients (paclitaxel+ramucirumab). Methods: The RAP trial (AIO-STO-0218, registered at ClinicalTrials.gov) is a single arm multicenter phase II trial. A total of 59 patients with metastatic or locally advanced gastric or gastro-esophageal junction adenocarcinoma, ECOG 0–1, who progressed after having received first-line therapy with platinum and fluoropyrimidine doublet with or without anthracycline, docetaxel or trastuzumab within the last six months will receive avelumab and ramucirumab on day 1, 15 and paclitaxel on day 1, 8 and 15 of a 28-day cycle until disease progression (RECIST v1.1), intolerable toxicity, withdrawal of consent or at a maximum treatment of 1 year. The primary endpoint is the overall survival rate (OSR) at 6 months. Sample size calculation is based on a Simon 2-stage design with a one-sided alpha error of 10% and a power of 80%, an expected OSR at 6 months of ≥ 65% and a 0 hypothesis ≤ 50%. Secondary endpoints include OS, OSR at 12 months, PFS, safety and tolerability, duration of response. Ethics commission approved the study protocol in January 2019. Updated patient accrual will be presented. Clinical trial information: AIO-STO-0218.
Databáze: OpenAIRE
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