Interim analysis of a phase II randomized clinical trial of samrium-153 (Sm-153) with or without PSA-TRICOM vaccine in metastatic castration-resistant prostate cancer after docetaxel.

Abstract

2526 Background: A prior randomized, placebo-controlled, multi-center phase 2 trial of PSA-TRICOM (PROSTVAC) demonstrated an overall survival benefit. Sm-153 is a radiopharmaceutical that targets osteoblastic bone lesions. Preclinical data indicated that Sm-153 could alter tumor phenotype, causing upregulation of Fas, MHC Class I, and tumor-associated antigens, making tumor cells more amenable to immune-mediated killing. Methods: This is a phase 2 multi-center trial design intended to randomize 68 patients (pts) to Sm-153 with or without PROSTVAC. Eligibility included castrate resistant prostate cancer bone metastases, no visceral disease, prior docetaxel, ECOG ≤2, and normal organ function. Sm-153 was given at 1mCi/kg IV on day 8 and then every 12 weeks. PROSTVAC was given on days 1, 15, 29, then every 4 weeks. The 1° endpoint is a comparison of progression-free survival at 4 months (mo) utilizing PCCWG, but not PSA criteria. 68 patients will provide 80% power to detect a difference of 15% vs. 40% without progression at 4 mo with a one-tailed alpha = 0.10 assuming Fisher’s exact test comparing these fractions as the primary method of analysis. 2° endpoints are OS, ORR, PSA changes, immunologic, toxicity, and palliation. Reported here is the result of a pre-specified interim analysis, which required ≥20% conditional power to detect 15% vs. 40% without progression at 4 months for the trial to continue. Results: Of 37 enrolled pts, 3 were not evaluable for PFS. PFS and PSA findings are found below. Hematologic toxicities (anemia, thrombocytopenia, neutropenia, or lymphocytopenia) are most common, with grade 3 or 4 thrombocytopenia occurring in 22% and 26% of treatment cycles on Arms A and B, respectively. The conditional power for the comparison of fractions without progression at 4 mo is 77%. Conclusions: This interim analysis suggests the combination of PROSTVAC and Sm-153 is well tolerated with similar toxicity profile to Sm-153 alone. The early indication of improved TTP warrants continued study accrual. [Table: see text]