765PD - Safety of Radium-223 Dichloride (Ra) with Docetaxel (D) in Patients (Pts) with Bone Metastases (Mets) from Castration-Resistant Prostate Cancer (Crpc): a Phase 1/2A Clinical Trial

Abstract

ABSTRACT Aim: Ra is an approved a-emitter that prolongs survival in pts with CRPC and symptomatic bone mets (Parker et al. NEJM. 2013). D is an approved chemotherapy for CRPC. We conducted a phase 1/2a study of Ra + D in CRPC pts with bone mets to establish safety and a recommended dose of the combination. We previously reported dose escalation data and recommended dose (ASCO 2013). Here we report preliminary data on an expansion cohort studying safety of Ra + D vs D alone. Methods: Eligible pts had progressing CRPC with ≥ 2 bone mets and were candidates for D treatment (tx). Pts were randomized 2:1 to the recommended dose (5 × Ra 50 kBq/kg q 6 wk + 10 × D 60 mg/m2 q 3 wk) vs D alone (75 mg/m2 q 3 wk with step-down option to 60 mg/m2). Adverse events were assessed during tx. Long-term safety data were collected q 3 mo for up to 1 year after start of study tx. Accrual is complete. Results: 46 pts are enrolled (dosed) in the expanded safety cohort. Baseline characteristics in the 2 tx arms are presented below (Table); 33 pts had Ra + D, and 13 had D alone. As of May 2014, 13 (Ra + D) vs 4 (D) pts had all planned study tx doses. To date, febrile neutropenia occurred in 2 pts (both had D alone). There were 1 case of grade 3/4 anemia (Ra + D), 2 cases of grade 1 anemia (both D alone), and no thrombocytopenia. Preliminary data for neutrophils and platelets (Table) indicate a nadir ∼ 1 week after injection, with values similar in the 2 tx arms. 3 of 4 pts receiving D had confirmed dose reductions. A safety review in Nov 2013 raised no concern; recommended Ra + D dose was continued. Patient Data and Characteristics From Expanded Safety Cohort Ra + Docetaxel n = 33 Docetaxel n = 13 No. of patients in treatment 10 4 No. of patients who discontinued study treatment 6 5 No. of patients in follow-up 13 4 No. of patients who completed study 4 0 Age, median (min-max), y 68 (49-82) 67 (55-82) Weight, median (min-max), kg 87 (58-119) 77 (67-131) PSA, median (min-max), mg/L 99 (3-1000) 43 (4-1042) Total ALP, median (min-max), mg/L 167 (62-1016) 284 (74-472) Bone ALP, median (min-max), mg/L 36 (10-331) 43(16-164) LDH, median (min-max), U/L 191 (123-418) 195 (124-328) Mean (min-max) nadir platelet count, thou/cumm, on treatment 261.9 (162-332) 231 (139-314) Mean (min-max) nadir absolute neutrophil count, thou/mL, on treatment 1.4 (0.2-5.5) 0.6 (0.1-1.2) Extent of disease 2-4 metastases 5-9 metastases 10-20 metastases > 20 metastases 3 6 9 11 0 3 4 6 Conclusions: The expanded safety cohort data confirm that Ra + D was well tolerated at 5 × Ra 50 kBq/kg q 6 wk + 10 × D 60 mg/m2 q 3 wk in pts who had all planned injections. More pts completed Ra + D tx vs D alone. Expanded safety cohort continues as planned. Disclosure: M.J. Morris: has had a consultant or advisory relationship with and has received research funding from Sanofi-Aventis and Algeta; C. Higano: Consultancy in the past 2-years from Bayer and Johnson & Johnson. Research funding from Algeta, Bayer and Janssen; H.I. Scher: D has had a consultancy relationship with Sanofi; D. Shevrin: Consulted with Astellas on Enzalutamide speakers Bureau for Astellas and Bayer C.J. Ryan: Consultancy: Bayer Adboard, Millenium Adboard Research funding: Algeta ASA (Bayer) Honoraria directly received from Janssen; Y. Loriot: has served as a consultant for Bayer, has received honoraria from Sanofi and Bayer, and has received research funding from Sanofi; K. Fizazi: has served on the speakers bureau or advisory committee for Sanofi and Bayer; J.E. Garcia-Vargas: is employed by Bayer HealthCare; K. Lyseng: M is employed by Algeta ASA (Bayer); M. Bloma: is employed by and has an ownership interest in Algeta ASA (Bayer); A. Aksnes: D is employed by Algeta ASA (Bayer); J.A. Carrasquillo: has had a consultant or advisory relationship with Bayer and has received honoraria and research funding from Algeta. All other authors have declared no conflicts of interest.