Pain Evaluation in Radium-223 Treated Castration Resistant Prostate Cancer Patients With Bone Metastases (PARABO)

PARABO - Pain Evaluation in Radium-223 (Xofigo®) Treated mCRPC Patients With Bone Metastases - a Non-interventional Study in Nuclear Medicine Centers

This observational prospective single arm cohort study is designed to assess pain and bone pain related quality of life of metastatic Castration Resistant Prostate Cancer (mCRPC) patients receiving Radium-223 in a real life nuclear medicine practice setting. In addition, overall survival, time to next tumor treatment (TTNT), time to first symptomatic skeletal event (SSE), course of blood counts, and safety will be assessed.

Study Overview

• Status: Completed
• Conditions: Castration-Resistant Prostatic Cancer
• Intervention / Treatment: Drug: Radium-223 dichloride, (Xofigo, BAY88-8223)

• Study Type: Observational
• Enrollment (Actual): 363

Contacts and Locations

Study Locations

• Germany
  • Multiple Locations, Germany

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of castration resistant prostate cancer patients with bone metastases treated with Radium-223.

Description

Inclusion Criteria:

• Adult male patients diagnosed with CRPC with symptomatic bone metastases without known visceral metastases
• Decision to initiate treatment with Radium-223 was made as per investigator's routine treatment practice

Exclusion Criteria:

• Patients participating in an investigational program with interventions outside of routine clinical practice or participating in another observational study with Xofigo

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Radium-223 dichloride; Male patients with a diagnosis of CRPC with symptomatic bone metastases without known visceral metastases will be enrolled after the decision for treatment with Radium-223 has been made by the attending physician according to his/her medical practice.	Drug: Radium-223 dichloride, (Xofigo, BAY88-8223); Dosage and treatment duration according to the decision of the treating physician

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain response	Determined by the worst pain item on the Brief Pain Inventory - Short Form (BPI-SF) patient questionnaire. A clinically meaningful pain response is defined as an improvement of two points from the baseline BPI-SF worst pain score at any post-baseline assessment.	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of pain over time	Determined by evaluating the worst pain item as well as the subscale scores for pain severity and pain interference as determined by patient responses on the BPI-SF questionnaire.	Up to 6 months from baseline
Change in bone pain related quality of life	As determined by patient responses on the bone pain specific Functional Assessment of Cancer Therapy Quality of Life Measurement in patients with bone pain (FACT-BP) questionnaire	Up to 6 months from baseline
Pain control rate	As determined by the worst pain item on the BPI-SF patient questionnaire. Pain control is defined as no increase by two points from the baseline BPI-SF worst pain score.	Up to 6 months
Pain progression rate	As determined by the worst pain item on the BPI-SF patient questionnaire. Pain progression is defined as an increase by two points from the baseline BPI-SF worst pain score at any post baseline assessment.	Up to 6 months
Time to first pain progression	Defined as the time between the first injection of Radium-223 until an increase in the BPI-SF worst pain item by at least two points	Up to 6 months
Time to first opioid use		Up to 5.5 years
Summary description of covariates on pain response	The following covariates will be analyzed: opioid use, assessment of extent of bone metastases, location of bone metastases,level of alkaline phosphatase at baseline, PSA (Prostate Specific Antigen) level at baseline, WHO pain score at baseline, pretreatment with chemotherapy (yes/no), pretreatment with deep androgen ablation by treatment with abiraterone or enzalutamide (yes/no), extent of bone uptake in known lesions, BSI	Up to 6 months
Relation between bone uptake in known lesions and pain palliation	Only in patients with bone scan prior to start of treatment and a second scan during or within 6 weeks after end of Radium-223 treatment	Up to 6 months
Dosage of Radium-223		Up to 5 months
Number of injections of Radium-223		Up to 5 months
Course of blood count presented as percentage of patients below limit for further injections according to the local product information		Up to 5 months
Number of participants with Treatment-emergent Adverse Events (TEAE)		Up to 6 months
Time to next tumor treatment(s) (TTNT)	Defined as the time from the first application of Radium-223 until start of next mCRPC treatment including e.g. chemotherapy and/or hormonal treatment	Up to 5.5 years
Time to first symptomatic skeletal event (SSE)	Defined as the time between the first injection of Radium-223 until the occurrence of first SSE defined as the first use of external beam radiation therapy to relieve skeletal symptoms, new symptomatic pathological vertebral or non-vertebral bone fractures, spinal cord compression, or tumor-related orthopedic surgical intervention	Up to 5.5 years
Overall survival	Defined as the time interval from the start of Radium-223 therapy to death, due to any cause. Patients alive at the end of the study will be censored at the last date known to be alive.	Up to 5.5 years
Bone Scan Index (BSI) as Imaging Biomarker in metastatic castration-resistant prostate cancer (mCRPC)	Evaluated by comparing BSI values before and after Radium-223 treatment as well as by investigating the association of BSI with other outcome parameters like OS	Up to 6 months
Effect of concomitant drug treatment on pain, quality of life, and overall survival	Exploration of the influence of abiraterone, enzalutamide, opioids and denosumab on OS by number of injections (5-6 vs. 1-4)	Up to 5.5 years
Time from castration resistance to treatment with Radium-223	Time from verified castration resistance to first injection of Radium-223	First treatment
Description of covariates on duration of therapy	Description of covariates on duration of therapy (to get ≥ 5 injections versus ≤ 4 injections) of mCRPC patients during treatment with Radium-223.	Up to 6 months
Factors positively influencing mCRPC patients to get ≥ 5 injections versus ≤ 4 injections	(e.g. concomitant use of antihormonal therapy, no pre-treatment of chemotherapy)	Up to 6 months
Incidence of pathological fractures, non-pathological fractures and bone associated events during treatment and follow up		Up to 5.5 years

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find results for studies related to Bayer products

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2015
• Primary Completion (Actual): May 20, 2020
• Study Completion (Actual): July 15, 2020

Study Registration Dates

• First Submitted: March 20, 2015
• First Submitted That Met QC Criteria: March 20, 2015
• First Posted (Estimate): March 25, 2015

Study Record Updates

• Last Update Posted (Actual): November 2, 2021
• Last Update Submitted That Met QC Criteria: November 1, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Radium-223; Bone metastases; Observational study; Hormone Refractory Prostatic Cancer; Xofigo
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Neoplastic Processes; Prostatic Neoplasms; Neoplasm Metastasis; Prostatic Neoplasms, Castration-Resistant; Antineoplastic Agents; Radium Ra 223 dichloride
• Other Study ID Numbers: 17550; XF1412DE (Other Identifier: Company internal)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No