217TiP - Dose-finding phase Ib study of FOLFOXIRI plus ramucirumab as first-line therapy for patients with metastatic colorectal cancer

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Kentaro Yamazaki
Citation Annals of Oncology (2016) 27 (suppl_9): ix53-ix67. 10.1093/annonc/mdw581
Authors K. Yamazaki1, Y. Kito1, T. Esaki2, H. Satake3, H. Taniguchi4, T. Tsuda5, T. Denda6, T. Moriwaki7, K. Mori8
  • 1Division Of Gastrointestinal Oncology, Shizuoka Cancer Center, 411-8777 - Shizuoka/JP
  • 2Department Of Gastrointestinal And Medical Oncology, National Kyushu Cancer Center, 811-1395 - Fukuoka/JP
  • 3Department Of Medical Oncology, Kobe City Medical Center General Hospital, 650-0047 - Kobe/JP
  • 4Department Of Clinical Oncology, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP
  • 5Division Of Clinical Oncology, St. Marianna University School of Medicine, 216-8511 - Kawasaki/JP
  • 6Gastroenterology, Chiba Cancer Center Hospital, 260-8717 - Chiba/JP
  • 7Faculty Of Medicine, Division Of Gastroenterology, University of Tsukuba, 305-8575 - Tsukuba/JP
  • 8Clinical Research Promotion Unit Of Clinical Research Center, Shizuoka Cancer Center, 411-8777 - Shizuoka/JP

Abstract

Background

The phase III TRIBE trial which compared FOLFOXIRI plus bevacizumab (Bmab) with FOLFIRI plus Bmab as first-line (1L) therapy (Tx) in pts with metastatic colorectal cancer (mCRC), recently demonstrated that the intensification of the chemotherapy backbone improved progression-free survival (PFS), overall response rate (ORR) and overall survival (OS), and increased the incidence of some adverse events. The phase III RAISE trial has shown the survival benefit of ramucirumab (Rmab) plus FOLFIRI compared with placebo plus FOLFIRI in patients (pts) who progressed during or after 1L Tx with Bmab, oxaliplatin (OX) and fluoropyrimidine. Rmab, an anti-VEGFR-2 monoclonal antibody, prevents ligands (not only VEGF-A, but also VEGF-C and D) binding and inhibits angiogenesis, although Bmab binds to and blocks circulating VEGF, especially VEGF-A. Therefore, Rmab may clinically inhibit angiogenesis more strongly than Bmab. This phase Ib study aims to determine recommended dose of phase II study.

Trial design

Eligibility criteria include histologically confirmed unresectable colorectal adenocarcinoma, age of 20-75 years, ECOG PS of 0–1 (PS of 0 if age of 71–75 years), without homozygous UGT1A1 *28 or *6, no history of prior chemotherapy, and adequate organ function. The primary endpoint is incidence of the dose-limiting toxicity (DLT) of FOLFOXIRI plus Rmab and the main secondary endpoints are ORR, PFS, OS and safety. Three dose levels of FOLFOXIRI plus Rmab are planned as follows; OX dose was fixed at 85 mg/m2. Level 1: 5-fluorouracil (5-FU) 3200mg/m2, irinotecan (IRI) 165mg/m2 and Rmab 8mg/kg, Level 0 as starting dose: 5-FU 2400mg/m2, IRI 150mg/m2 and Rmab 8mg/kg, and Level -1: 5-FU 2400mg/m2, IRI 120mg/m2 and Rmab 8mg/kg. Patients undergo a 3 + 3 design schema to evaluate the DLT. The recommended dose is defined as the highest dose level where no more than 2 of 6 patients experience a DLT during the first cycle. Seven institutions are participating in this study. This study is registered to the University Hospital Medical Information Network, number UMIN000023277, and activated in July 2016.

Clinical trial indentification

The University Hospital Medical Information Network, number UMIN000023277

Legal entity responsible for the study

Shizuoka Cancer Center

Funding

Shizuoka Cancer Center

Disclosure

K. Yamazaki: Lecture fee from Chugai, Takeda, Taiho, Yakult, Daiichi-Sankyo, Merck serono, Bristol, Eli Lilly. All other authors have declared no conflicts of interest.