title: A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma.
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.
  
  
  BACKGROUND
  NCT00444782.
authors.affiliation: Department of Gastroenterology, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany. tim.greten@nih.gov
authors.forename: Tim F
authors.initials: TF
authors.lastname: Greten
authors.forename: Alejandro
authors.initials: A
authors.lastname: Forner
authors.forename: Firouzeh
authors.initials: F
authors.lastname: Korangy
authors.forename: Gisele
authors.initials: G
authors.lastname: N'Kontchou
authors.forename: Nathalie
authors.initials: N
authors.lastname: Barget
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
authors.forename: Lars A
authors.initials: LA
authors.lastname: Ormandy
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Michel
authors.initials: M
authors.lastname: Beaugrand
authors.forename: Jordi
authors.initials: J
authors.lastname: Bruix
mesh_terms: D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007271:Injections, Intradermal; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000201:enzymology / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D019098:Telomerase / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D019496:Cancer Vaccines; D010446:Peptide Fragments; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; C514987:GV1001 peptide; D019098:Telomerase