Randomized phase II trial of weekly paclitaxel + ramucirumab versus weekly nab-paclitaxel + ramucirumab for unresectable advanced or recurrent gast...

Date 29 September 2019
Event ESMO 2019 Congress
Session Poster Display session 2
Topics Gastric Cancer
Presenter Kenro Hirata
Citation Annals of Oncology (2019) 30 (suppl_5): v253-v324. 10.1093/annonc/mdz247
Authors K. Hirata1, Y. Hamamoto2, K. Tsuchihashi3, C. Kondoh4, K. Yamazaki5, S. Hironaka6, M. Ando7, C.K. Imamura8, K. Yoshimura9, K. Muro10
  • 1Division Of Gastroenterology And Hepatology, Department Of Internal Medicine, Keio University School of Medicine, 160-0016 - Tokyo/JP
  • 2Keio Cancer Center, Keio University School of Medicine, 160-8582 - Tokyo/JP
  • 3Department Of Medicine And Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 812-8582 - Fukuoka/JP
  • 4Department Of Medical Oncology, Toranomon Hospital, 105-8470 - Tokyo/JP
  • 5Gastroenterology, Sizuoka Cancer Center, 4118777 - Sundogun/JP
  • 6Department Of Medical Oncology And Hematology, Oita University, 879-5593 - Oita/JP
  • 7Center For Advanced Medicine And Clinical Research, Nagoya University Hospital, 466-8550 - Nagoya/JP
  • 8Department Of Clinical Pharmacokinetics And Pharmacodynamics, Keio University School of Medicine, 160-8582 - Tokyo/JP
  • 9Innovative Clinical Research Center, Kanazawa University, 920-8641 - Kanazawa/JP
  • 10Department Of Clinical Oncology, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP

Abstract

Background

Ramucirumab (RAM) with weekly paclitaxel (wPTX) is the recommended standard second-line therapy for advanced and recurrent gastric cancer (GC). In a recent phase II study, wNab-PTX + RAM combination for GC showed promising safety and efficacy, but it remains unclear whether wPTX + RAM or wNab-PTX + RAM should be used as second-line therapy. The previous ABSOLUTE Trial compared triweekly Nab-PTX, wNab-PTX, and wPTX in patients with advanced/recurrent GC as second-line therapy. Subgroup analysis of subjects with peritoneal dissemination (52.8%) showed that the hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) in the wNab-PTX arm compared with the wPTX arm were 0.78 and 0.64, respectively. Therefore, we are investigating whether wNab-PTX + RAM is more effective than wPTX + RAM for patients with peritoneal dissemination.

Trial design

WJOG10617G/P-SELECT is an open-label, randomized, phase II study evaluating wPTX + RAM (arm A) versus wNab-PTX + RAM (arm B). Key eligibility criteria: 1) Histological diagnosis of primary GC, 2) unresectable or recurrent GC, 3) patients with peritoneal dissemination, 4) intolerant or refractory to first-line therapy including a fluoropyrimidine, and 5) ECOG Performance Status (PS) 0-2. Stratification factors are: institution, PS, and severity of ascites. Arm A comprises PTX 80 mg/m2(day 1,8,15) and RAM 8 mg/kg (day 1,15) every 4 weeks. Arm B comprises Nab-PTX 100 mg/m2(day 1,8,15) instead of PTX. The primary endpoint is OS, and the main secondary endpoints are PFS, objective response rate (ORR), safety, and neuropathy-specific quality of life (QOL). SPARC and Caveolin-1 (Cav-1) expression in tumor tissues will be evaluated as predictive biomarkers for efficacy. Pharmacokinetics of RAM will also be assessed. The required sample size for the full analysis was 50 patients per group to maintain a probability of 70% or higher that the HR for OS in arm B would be lower than 0.90. Enrollment was therefore set at 105 subjects. This study has enrolled 26 patients as of March 31, 2019.

Clinical trial identification

jRCTs031180022, 27 September 2018.

Editorial acknowledgement

Legal entity responsible for the study

WJOG (West Japan Oncology Group).

Funding

Taiho Pharmaceutical Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.