A Phase II Open Label Trial Evaluating Safety and Efficacy of a Telomerase Peptide Vaccination in Patients with Advanced Hepatocellular Carcinoma

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2010 May 19

PMID 20478057

Citations 97

Authors

Tim F Greten

Alejandro Forner

Firouzeh Korangy

Gisele Nkontchou

Nathalie Barget

Carmen Ayuso

Lars A Ormandy

Michael P Manns

Michel Beaugrand

Jordi Bruix

Affiliations

Soon will be listed here.

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.

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