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

Study Overview
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Brief Summary
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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.

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

Conditions
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Castration-Resistant Prostatic Cancer

Intervention / Treatment
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* Drug: Radium-223 dichloride, (Xofigo, BAY88-8223)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Radium-223 dichloride<br>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)<br>* Dosage and treatment duration according to the decision of the treating physician<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Observational study, Bone metastases, Hormone Refractory Prostatic Cancer, Radium-223, Xofigo