Abstract OT2-01-05: A phase 2 randomized, double-blind, placebo-controlled trial of hormone therapy ± radium-223 dichloride in human epidermal growth factor receptor 2–negative, hormone receptor–positive breast cancer patients with bone metastases
Authors: Coleman RE , Huang L , Petrenciuc O , Zaccarini P , Rugo HS 
Published: May 2016

Abstract
Background: Treatment options for bone-metastatic breast cancer (MBC) are limited. Multimodality therapy may improve symptom control and survival. In a phase 2a study of advanced breast cancer patients with bone-dominant and no visceral disease, radium-223 dichloride (radium-223), a first-in-class α-emitter selectively targeting bone metastases, reduced baseline bone biomarker levels with favorable safety (Coleman et al. Breast Cancer Res Treat 2014). This study (NCT02258464) evaluates efficacy and safety of radium-223 versus placebo in human epidermal growth factor receptor 2–negative (HER2-), hormone receptor–positive (HR+) bone-MBC patients receiving single-agent hormone therapy.
Trial design: Patients receive (1:1) radium-223 50 kBq/kg IV or placebo q 4 wk (6 cycles) + concurrent single-agent hormone therapy + best supportive care. Stratification is by geographic region, prior lines of hormone therapy for MBC, and number of prior skeletal events.
Main eligibility criteria: Eligible patients are pre- or postmenopausal with estrogen receptor–positive, HER2-, bone-dominant MBC with ≥ 2 bone metastases and ≥ 1 or 2 prior symptomatic skeletal events (external beam radiotherapy for bone pain, pathologic bone fracture, spinal cord compression, orthopedic surgery). Patients had ≥ 1 line of hormone therapy for MBC; are taking bisphosphonates or denosumab for ≥ 1 month before study; are eligible for endocrine treatment; and have evaluable disease (RECIST v1.1), asymptomatic or mildly symptomatic bone disease (Brief Pain Inventory), ECOG performance status 0-1, and adequate hematologic, renal, and liver function. Patients may not have had visceral or brain metastases or leptomeningeal disease, need for chemotherapy for metastases, and untreated spinal cord compression.
Specific aims: Patients are assessed for efficacy and safety, and followed to symptomatic skeletal events, radiologic progression, death, or withdrawal. Primary endpoint is symptomatic skeletal event–free survival.
Statistical methods: Assuming a 1-sided α of 0.1, power of 90%, ∼ 119 symptomatic skeletal events are required for the analysis. Time-to-event variables will be analyzed using a log-rank test, accounting for stratification. Kaplan-Meier estimates and survival curves will be given for each treatment group. Safety analyses will be descriptive.
Present and target accruals: As of May 2015, 5 patients have been screened and 3 enrolled. Target enrollment is 227 patients.
Citation Format: Coleman RE, Huang L, Petrenciuc O, Zaccarini P, Rugo HS. A phase 2 randomized, double-blind, placebo-controlled trial of hormone therapy ± radium-223 dichloride in human epidermal growth factor receptor 2–negative, hormone receptor–positive breast cancer patients with bone metastases. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT2-01-05.