A phase ΙI study of five peptides combination with oxaliplatin-based chemotherapy as a first-line therapy for advanced colorectal cancer (FXV study)

Shoichi Hazama, Yusuke Nakamura, Hiroaki Tanaka, Kosei Hirakawa, Ko Tahara, Ryoichi Shimizu, Hiroaki Ozasa, Ryuichi Etoh, Fumiaki Sugiura, Kiyotaka Okuno, Takumi Furuya, Taku Nishimura, Koichiro Sakata, Kazuhiko Yoshimatsu, Hiroko Takenouchi, Ryouichi Tsunedomi, Yuka Inoue, Shinsuke Kanekiyo, Yoshitaro Shindo, Nobuaki SuzukiShigefumi Yoshino, Hirokazu Shinozaki, Akira Kamiya, Hiroyuki Furukawa, Takeharu Yamanaka, Tomonobu Fujita, Yutaka Kawakami, Masaaki Oka

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72 Citations (Scopus)


Background: We previously conducted a phase I trial for advanced colorectal cancer (CRC) using five HLA-A*2402-restricted peptides, three derived from oncoantigens and two from vascular endothelial growth factor (VEGF) receptors, and confirmed safety and immunological responses. To evaluate clinical benefits of cancer vaccination treatment, we conducted a phase II trial using the same peptides in combination with oxaliplatin-based chemotherapy as a first-line therapy.Methods: The primary objective of the study was the response rates (RR). Progression free survival (PFS), overall survival (OS), and immunological parameters were evaluated as secondary objective. The planned sample size was more than 40 patients for both HLA2402-matched and -unmatched groups. All patients received a cocktail of five peptides (3 mg each) mixed with 1.5 ml of IFA which was subcutaneously administered weekly for the first 12 weeks followed by biweekly administration. Presence or absence of the HLA-A*2402 genotype were used for classification of patients into two groups.Results: Between February 2009 and November 2012, ninety-six chemotherapy naïve CRC patients were enrolled under the masking of their HLA-A status. Ninety-three patients received mFOLFOX6 and three received XELOX. Bevacizumab was added in five patients. RR was 62.0% and 60.9% in the HLA-A*2402-matched and -unmatched groups, respectively (p = 0.910). The median OS was 20.7 months in the HLA-A*2402-matched group and 24.0 months in the unmatched group (log-rank, p = 0.489). In subgroup with a neutrophil/lymphocyte ratio (NLR) of < 3.0, patients in the HLA-matched group did not survive significantly longer than those in the unmatched group (log-rank, p = 0.289) but showed a delayed response.Conclusions: Although no significance was observed for planned statistical efficacy endpoints, a delayed response was observed in subgroup with a NLR of < 3.0. Biomarkers such as NLR might be useful for selecting patients with a better treatment outcome by the vaccination.Trial registration: Trial registration: UMIN000001791.

Original languageEnglish
Article number108
JournalJournal of Translational Medicine
Issue number1
Publication statusPublished - 2014 Apr 30
Externally publishedYes


  • Chemotherapy
  • Colorectal cancer
  • Peptide cocktail
  • Peptide vaccine
  • Phase II study

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology


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