A MULTICENTER, RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND TRIAL WITH VEGFR2-EPITOPE PEPTIDE AND GEMCITABINE FOR PATIENTS WITH LOCALLY ADVANCED, METASTATIC, OR UNRESECTABLE PANCREATIC CANCER: PEGASUS-PC STUDY

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Abstract

Background

Gemcitabine is a key drug for treating pancreatic cancer; however, with the limitation in clinical benefits, the development of another potent therapeutic was strongly called for. VEGF-receptor 2 (VEGFR2: Flk-1 and KDR) is an essential target for tumor angiogenesis, and we have executed a phase I clinical trial using gemcitabine and VEGFR2-pepide (Cancer Sci 2010). Based on promising phase I trial results, a multicenter, randomized, placebo-controlled, double-blind phase II/III clinical trial has been conducted (UMIN000001664).

Methods

The eligibility criteria are: locally advanced, metastatic, or unresectable pancreatic cancer. Patients were allocated to either VEGFR2 peptide (OTS102) + gemcitabine group or placebo + gemcitabine in 2:1 ratio by dynamic allocation method. The primary end point was overall survival. The Harrington–Fleming test, with the weight proportional to cumulative death probability, was used for the statistical analysis under the time-lagged effect of immunotherapy. Sample size was estimated presuming the effects will be observed from the time point of 50% cumulative survival rate. Assuming a type I error α (two-sided) level of 5% and a power of 80% or more for 50–60% reduction of hazard, sample size necessary was estimated as 100 patients for the active group and 50 patients for the placebo group.

Results

No statistically significant survival time prolongation was observed in OTS102 add-on group. However, the subgroup analysis revealed significant interaction between the treatment and reports of ulcerations in add-on group.

Conclusion

Despite the lack of survival time prolongation by OTS102 add-on to gemcitabine therapy, patients experienced injection site ulcerations may have better survival, suggesting new prognostic factors for VEGFR2-epitope peptide. Our results indicate the possibility of epitope peptide used in cocktail therapies.

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