Multi-center phase II/III randomized controlled clinical trial using TNFerade combined with chemoradiation in patients with locally advanced pancreatic cancer (LAPC)

4518 Background: TNFerade is a replication-deficient adenoviral vector carrying the transgene for human TNF-a protein, regulated by the radiation-inducible promoter Egr-1. A 50 patient (pt) phase II dose-escalation study in LAPC showed a possible dose-dependent improvement in survival. To confirm these findings, the randomized Pancreatic Cancer Clinical Trial with TNFerade (PACT) study was developed. PACT is a 330 pt study, powered to detect a 20% absolute increase in the primary efficacy endpoint (overall survival at 1 year) compared to standard of care (SOC) chemoradiation. An interim analysis of safety and efficacy was planned after the first 51 pts were randomized. Survival data to 11/15/06 has been evaluated and are reported here. Methods: The TNFerade arm pts received a five- wk treatment of weekly injections of 4 x 1011 pu TNFerade, continuous infusion 5-FU (200 mg/m2/day x 5 days/wk) and 50.4 Gy radiation. TNFerade was administered by percutaneous CT-guided transabdominal injection. The SOC arm received the same regimen, without TNFerade injections. Patients were randomized 2:1 to the TNFerade and SOC arms. The first 51 randomized pts were assessed for evidence of objective response (OR) and overall survival Results: Assessment of response data is still ongoing. TNFerade + SOC was well tolerated. One year survival, the primary endpoint of the study, was 70.5% in the TNFerade + SOC arm versus 28.0% in the SOC arm, an absolute increase of 42.5%. The median survival for TNFerade + SOC pts was 515 days compared to 335 days for the SOC pts. The logrank statistic for comparison between the two arms is X2 = 2.014 (p=0.16). Conclusions: The interim survival data is preliminary. The magnitude of the difference in survival in favor of the TNFerade + SOC arm, however, is encouraging. The data appears to corroborate previous findings from the dose-escalation study, which showed an apparent survival advantage in the 4×1011 pu dose group compared to 4 x 109 pu group. A second interim analysis is planned with larger patient numbers to determine whether this early positive trend is confirmed. No significant financial relationships to disclose.