Registry of Treatment Outcomes of Symptomatic Metastasized Castration Resistant Prostate Cancer Treated With Radium-223

Bone Metastases Clinical Trial

— ROTOR  

Official title:

Registry of Treatment Outcomes in a Non-study Population of Symptomatic Metastasized Castration Resistant Prostate Cancer (mCRPC) Patients Treated With Radium-223

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03223597
• Other study ID #: m14ROT
• Status: Completed
• Start date: January 17, 2015
• Est. completion date: March 1, 2018

Study information

• Verified date: July 2017
• Source: The Netherlands Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Radium-223 is the 5th treatment for metastasized castration resistant prostate cancer with a proven overall survival benefit. The improved survival of Radium-223 over placebo was demonstrated in the ALSYMPCA trial, which included a miscellaneous patient population both docetaxel pretreated and non-pretreated. This registry aims to describe non-study patients treated with Radium-223 and prospectively evaluate treatment outcomes of patients with and without docetaxel pretreatment. Analgesic use and patient reported pain scores, efficacy of the subsequent therapy and overall survival will be evaluated. Moreover, clinical and explorative serum and blood biomarkers of Radium-223 efficacy will be explored.

Description:

Every year approximately 12,000 men are diagnosed with prostate cancer in the Netherlands and approximately 2,400 die of this disease. When prostate cancer is limited to the prostate, patients can be operated or radiated with a curative intention, however, metastasized disease is incurable. Initially, prostate cancer responds to testosterone at castration level and treatment with androgen receptor signaling inhibitors. However, after an average of 24 months, prostate cancer will reach a castration resistant stage (mCRPC), which is associated with high morbidity and mortality. Since the introduction of Docetaxel in 2004, multiple treatments for mCRPC have become available. All these treatments have a proven beneficial effect on quality of life and all expand life expectancy. An important clinical problem is that approximately 50% of older patients are not able or not willing to receive docetaxel treatment. These patients are also not eligible for treatments of docetaxel refractory disease. Therefore, there is a need for effective treatments with little site effects.

In the phase 3, ALSYMPCA study 921 patients were randomized between Rad-223 (Xofigo®) and placebo in a 2:1 distribution1. Patients with symptomatic bone metastases, limited lymph node involvement, adequate bone marrow, kidney and liver functions were included in this trial. Patients were previously treated with docetaxel or could not receive docetaxel, declined docetaxel or docetaxel was not available. At a planned interim analysis after 538 deaths, the primary end point overall survival (OS) was 14.9 months in the Radium-223 treated arm and 11.3 months in the placebo arm (HR 0.70; 95% CI 0.58-0.83). All secondary end points were at the favor of Radium-223 treated patients, including time to first skeletal related event, quality of life and various biochemical end points. However, patient reported pain scores were not collected in the trial. Radium-223 treatment was well tolerated, with the most prominent side effects (all grades) thrombocytopenia 12 and 6%, neutropenia 5 and 1% and diarrhea 25 and 15% in the Radium-223 and placebo arm, respectively.

A post-hoc analysis showed an equal efficacy of Radium-223 treatment in docetaxel pre-treated patients as in docetaxel naïve patients.

In this registry the investigators aim to evaluate the efficacy of Radium-223 treatment and first subsequent therapy in a non-study population. Various parameters will be collected, including changes in patient reported pain score. Moreover, changes in serum and blood levels of biomarkers of bone metabolism and levels of blood osteoclast precursors in Radium-223 treated patients will be evaluated for their potential to predict treatment outcome.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: March 1, 2018
• Est. primary completion date: February 1, 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• At the physicians discretion

Exclusion Criteria:

• At the physicians discretion

• Radium-223 treatment in combination with another life-prolonging agent

Related Conditions & MeSH terms

• Bone Metastases
• Neoplasm Metastasis
• Prostate Cancer Metastatic
• Prostatic Neoplasms

Intervention

Drug:
• Radium-223 dichloride
Registry of patients who receive Radium-223.

Locations

Country	Name	City	State
Netherlands	Jeroen Bosch Hospital	's Hertogenbosch
Netherlands	Noordwest Ziekenhuisgroep	Alkmaar
Netherlands	Zorggroep Twente	Almelo
Netherlands	Meander Medical Center	Amersfoort	Utrecht
Netherlands	The Netherlands Cancer Intitute	Amsterdam
Netherlands	Rijnstate	Arnhem
Netherlands	Amphia Ziekenhuis	Breda
Netherlands	Reinier de Graaf Hospital	Delft
Netherlands	Deventer Ziekenhuis	Deventer
Netherlands	Catharina Ziekenhuis	Eindhoven
Netherlands	Groene Hart Ziekenhuis	Gouda
Netherlands	Martini Ziekenhuis	Groningen
Netherlands	Atrium Medisch Centrum Parkstad	Heerlen
Netherlands	Spaarne Gasthuis	Hoofddorp
Netherlands	Antonius Ziekenhuis	Nieuwegein
Netherlands	Franciscus Gasthuis-Vlietland	Rotterdam
Netherlands	Haga Ziekenhuis	The Hague
Netherlands	MC Haaglanden	The Hague
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Netherlands	Isala Klinieken	Zwolle

Sponsors (2)

Lead Sponsor	Collaborator
The Netherlands Cancer Institute	Bayer

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reported analgesic use and pain outcome	Evaluate Radium-223 treatment efficacy by patient reported analgesic use and pain outcome, assessed by BPI-S, FACT-P and questionnaire about analgesic use.	through study completion, an average of 1 year. (6 months treatment, 6 months follow-up after end of treatment)
Secondary	Efficacy on clinical parameters of treatment with Radium-223	Evaluate Radium-223 treatment efficacy in a non-study population of CRPC patients by clinical parameters, through patient records (WHO PS)	through study completion, an average of 1 year. (6 months treatment, 6 months follow-up after end of treatment)
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Evaluate Radium-223 treatment tolerability in a non-study population of CRPC patients, through patient records (using the CTCAE v4.03 for adverse events).	through study completion, an average of 1 year. (6 months treatment, 6 months follow-up after end of treatment)
Secondary	Subsequent therapy after Radium-223: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Evaluate of the treatment after Radium-223 the treatment tolerability in a non-study population of CRPC patients, through patient records (using the CTCAE v4.03 for adverse events).	through study completion, an average of 1 year. (6 months treatment, 6 months follow-up after end of treatment)
Secondary	Efficacy of subsequent treatment on clinical parameters	Evaluate the subsequent treatment efficacy in a non-study population of CRPC patients by clinical parameters, through patient records (WHO PS) But also by patient records (recors of bonescans, CT scans, blood measurements, out-patient clinic visits).	through study completion, an average of 1 year. (6 months treatment, 6 months follow-up after end of treatment)
Secondary	Symptomatic Skeletal Events	To evaluate the efficacy of Radium-223 treatment in a nonstudy population by effects on Symptomatic Skeletal Event (SSE). Through patient records and questionnairs (FACT-P, BPI-S and use of painmedication)	through study completion, an average of 1 year. (6 months treatment, 6 months follow-up after end of treatment)
Secondary	Evaluate the efficacy of Radium-223 by patient records	Records of bonescans, CT scans, blood measurements, this will all be combined in one reported value; Progressve disease, stable disease, partial remission or complete remission.	through study completion, an average of 1 year. (6 months treatment, 6 months follow-up after end of treatment)