A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma

BMC Cancer. 2010 May 17;10:209. doi: 10.1186/1471-2407-10-209.

Abstract

Background: The sole effective option for patients with advanced HCC is sorafenib and there is an urgent need to develop new therapeutic approaches. Immunotherapy is a promising option that deserves major investigation. In this open label, single arm clinical trial, we analyzed the effect of a low dose cyclophosphamide treatment in combination with a telomerase peptide (GV1001) vaccination in patients with advanced HCC.

Methods: 40 patients with advanced HCC were treated with 300 mg/m2 cyclophosphamide on day -3 followed by GM-CSF + GV1001 vaccinations on days 1, 3, 5, 8, 15, 22, 36 followed by 4-weekly injections. Primary endpoint of this phase II trial was tumor response; secondary endpoints evaluated were TTP, TTSP, PFS, OS, safety and immune responses.

Results: None of the patients had a complete or partial response to treatment, 17 patients (45.9%) demonstrated a stable disease six months after initiation of treatment. The median TTP was 57.0 days; the median TTSP was estimated to be 358.0 days. Cyclophosphamide, GV1001 and GM-CSF treatment were well tolerated and most adverse events, which were of grade 1 or 2, were generally related to the injection procedure and injection site reactions. GV1001 treatment resulted in a decrease in CD4+CD25+Foxp3+ regulatory T cells; however, no GV1001 specific immune responses were detected after vaccination.

Conclusions: Low dose cyclophosphamide treatment followed by GV1001 vaccinations did not show antitumor efficacy as per tumor response and time to progression. Further studies are needed to analyze the effect of a combined chemo-immunotherapy to treat patients with HCC.

Trial registration: NCT00444782.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / therapeutic use*
  • Carcinoma, Hepatocellular / enzymology
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Europe
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Humans
  • Infusions, Intravenous
  • Injections, Intradermal
  • Kaplan-Meier Estimate
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / immunology
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Male
  • Middle Aged
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / adverse effects
  • Peptide Fragments / therapeutic use*
  • T-Lymphocytes, Regulatory / immunology
  • Telomerase / administration & dosage
  • Telomerase / adverse effects
  • Telomerase / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Alkylating
  • Cancer Vaccines
  • Peptide Fragments
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Cyclophosphamide
  • GV1001 peptide
  • Telomerase

Associated data

  • ClinicalTrials.gov/NCT00444782