Clinical trial NCT03223597: Registry of Treatment Outcomes of Symptomatic Metastasized Castration Resistant Prostate Cancer Treated With Radium-223
Official title: Registry of Treatment Outcomes in a Non-study Population of Symptomatic Metastasized Castration Resistant Prostate Cancer (mCRPC) Patients Treated With Radium-223
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Prostate Cancer Metastatic
Bone Metastases
Keywords: Radium-223
quality of life
Pain
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2017-07-21
Enrollment: 300
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with metastasized castration resistant prostate cancer (mCRPC), who have bone metastases and no visceral metastases and receive Radium-223 according to the physician's discretion

Brief 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.

Detailed 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.

Eligibility criteria: Inclusion Criteria:

* At the physicians discretion

Exclusion Criteria:

* At the physicians discretion
* Radium-223 treatment in combination with another life-prolonging agent

Primary outcomes:
measure: Reported analgesic use and pain outcome
timeFrame: through study completion, an average of 1 year. (6 months treatment, 6 months follow-up after end of treatment)
Secondary outcomes:
measure: Efficacy on clinical parameters of treatment with Radium-223
timeFrame: through study completion, an average of 1 year. (6 months treatment, 6 months follow-up after end of treatment)
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: through study completion, an average of 1 year. (6 months treatment, 6 months follow-up after end of treatment)
measure: Subsequent therapy after Radium-223: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: through study completion, an average of 1 year. (6 months treatment, 6 months follow-up after end of treatment)
measure: Efficacy of subsequent treatment on clinical parameters
timeFrame: through study completion, an average of 1 year. (6 months treatment, 6 months follow-up after end of treatment)
measure: Symptomatic Skeletal Events
timeFrame: through study completion, an average of 1 year. (6 months treatment, 6 months follow-up after end of treatment)
measure: Evaluate the efficacy of Radium-223 by patient records
timeFrame: through study completion, an average of 1 year. (6 months treatment, 6 months follow-up after end of treatment)
Other outcomes:
Locations:
city: Amersfoort
country: Netherlands
facility: Meander Medical Center
state: Utrecht
city: 's Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Hospital
city: Alkmaar
country: Netherlands
facility: Noordwest Ziekenhuisgroep
city: Almelo
country: Netherlands
facility: Zorggroep Twente
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Intitute
city: Arnhem
country: Netherlands
facility: Rijnstate
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis
city: Delft
country: Netherlands
facility: Reinier de Graaf Hospital
city: Deventer
country: Netherlands
facility: Deventer Ziekenhuis
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Gouda
country: Netherlands
facility: Groene Hart Ziekenhuis
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis
city: Heerlen
country: Netherlands
facility: Atrium Medisch Centrum Parkstad
city: Hoofddorp
country: Netherlands
facility: Spaarne Gasthuis
city: Nieuwegein
country: Netherlands
facility: Antonius Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Franciscus Gasthuis-Vlietland
city: The Hague
country: Netherlands
facility: Haga Ziekenhuis
city: The Hague
country: Netherlands
facility: MC Haaglanden
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Zwolle
country: Netherlands
facility: Isala Klinieken
Study officials:
affiliation: The Netherlands Cancer Institute
name: Andre Bergman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: