RADIUM-223

Introduction

Based on the survival results of a randomized phase 3 trial in 2013, the European Medicines Agency (EMA) has approved radium-223 for the treatment of metastatic castration resistant prostate cancer (mCRPC) with bone metastases only. However, as traditional parameters, including PSA, fail in (early) response evaluation, other parameters are needed to guide treatment planning in mCRPC patients, treated with radium-223. In addition, previous studies have shown that radium-223 can induce immune responses, indicating that radium-223 may improve the efficacy of immune checkpoint inhibition.

Aim of the study

The Radium223Insight study aims to identify biomarkers for early identification of clinical benefit from radium-223 treatment and to better understand immune response during radium-223 treatment in mCRPC patients.

Study design Radium223Insight

The Radium223Insight is a collaborative effort of the Erasmus MC Rotterdam, Radboud UMC Nijmegen and the Franciscus Gasthuis & Vlietland Hospital, Rotterdam. Within the Radium223Insight, 30 patients will be included. Patients will be treated with radium-223 according to standard of care, while carefully being monitored by obtaining multi-parametric parameters from blood, imaging and tissue.

Early response evaluation

To improve early response evaluation of treatment with radium-223, circulating tumor cells and circulating tumor DNA in longitudinal blood samples will be investigated. In addition to standard computed tomography (CT) and bone scintigraphy, positron emission tomography (PET) using 68Ga-PSMA will be performed prior, during and after treatment with radium-223. Besides, 68Ga-PSMA-guided bone biopsies will be performed in order to collect tumor tissue for whole genome sequencing.

Radium-223 induced immune response

To evaluate the radium-223-induced immune response in vivo, 89Zr-atezolizumab PET will be performed at baseline and after 12 weeks of treatment. In addition, immune cells will be collected from blood, and tissue from bone biopsies will be analyzed using multiplex immunohistochemical stainings.

This study is funded by a grant from Bayer, a grant from Foundation Dutch Uro-Oncology Studygroup and ‘Running Stairs for Cancer’, a fundraising action.

Internal collaborations

Department of Medical Oncology

• Laboratory of prof. dr. John Martens (Circulating tumor cells and circulating tumor DNA)
• Laboratory of dr. Reno Debets (Tumor Immunology)

Department of Radiology and Nuclear Medicine

• Cancer Computational Biology Center

External collaborations

Radboud UMC Nijmegen

• Department of Medical Oncology
• Department of Radiology and Nuclear Medicine
• Laboratory of prof. dr. Jolanda de Vries (Tumor Immunology)

Franciscus Gasthuis & Vlietland

• Department of Internal Medicine

UMC Groningen

• Department of Medical Oncology
• Department of Radiology and Nuclear Medicine

Hartwig Medical Foundation

• Dr. Astrid van der Veldt, PI
• Drs. Anouk de Jong, study coordinator
• Dr. Martijn Lolkema
• Drs. Debbie Robbrecht
• Prof. dr. Ronald de Wit
• Prof. dr. John Martens 
• Prof. dr. Reno Debets 
• Dr. Tessa Brabander
• Dr. Paul Hamberg
• Dr. Niven Mehra

Contact? Mail study coordinator Anouk de Jong.