A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma
1 Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
2 Twincore Center for Experimental and Clinical Infection Research, Feodor-Lynen Strasse 7-9, 30625 Hannover, Germany
3 Service d'Hepato-Gastroenterologie, Hopital Jean Verdier AP-HP, Universite' Paris XIII, Bondy 93143, Cedex, France
4 BCLC Group, Liver Unit, Hospital Clínic. University of Barcelona. IDIBAPS. CIBEREHD. Villarroel 170, Barcelona 08036, Spain
5 Department of Legal Medicine, University Medical Center Göttingen, Robert-Koch-Straße 40, 37075 Göttingen, Germany
6 Medical Oncology Branch, National Cancer Institute, NIH, Bldg. 10 Rm 12N226, 9000 Rockville Pike, Bethesda MD 20892, USA
BMC Cancer 2010, 10:209 doi:10.1186/1471-2407-10-209Published: 17 May 2010
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.
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.
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.
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.