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

• ClinicalTrials.gov Identifier: NCT02398526
• Recruitment Status: Completed
• First Posted: March 25, 2015
• Last Update Posted: November 2, 2021
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Castration-Resistant Prostatic Cancer	Drug: Radium-223 dichloride, (Xofigo, BAY88-8223)

Study Design

• Study Type: Observational
• Actual Enrollment: 363 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: PARABO - Pain Evaluation in Radium-223 (Xofigo®) Treated mCRPC Patients With Bone Metastases - a Non-interventional Study in Nuclear Medicine Centers
• Actual Study Start Date: March 19, 2015
• Actual Primary Completion Date: May 20, 2020
• Actual Study Completion Date: July 15, 2020

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

1. Pain response [ Time Frame: Up to 6 months ]
   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.

Secondary Outcome Measures :

1. Change of pain over time [ Time Frame: Up to 6 months from baseline ]
   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.
2. Change in bone pain related quality of life [ Time Frame: Up to 6 months from baseline ]
   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
3. Pain control rate [ Time Frame: Up to 6 months ]
   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.
4. Pain progression rate [ Time Frame: Up to 6 months ]
   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.
5. Time to first pain progression [ Time Frame: Up to 6 months ]
   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
6. Time to first opioid use [ Time Frame: Up to 5.5 years ]
7. Summary description of covariates on pain response [ Time Frame: Up to 6 months ]
   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
8. Relation between bone uptake in known lesions and pain palliation [ Time Frame: Up to 6 months ]
   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
9. Dosage of Radium-223 [ Time Frame: Up to 5 months ]
10. Number of injections of Radium-223 [ Time Frame: Up to 5 months ]
11. Course of blood count presented as percentage of patients below limit for further injections according to the local product information [ Time Frame: Up to 5 months ]
12. Number of participants with Treatment-emergent Adverse Events (TEAE) [ Time Frame: Up to 6 months ]
13. Time to next tumor treatment(s) (TTNT) [ Time Frame: Up to 5.5 years ]
    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
14. Time to first symptomatic skeletal event (SSE) [ Time Frame: Up to 5.5 years ]
    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
15. Overall survival [ Time Frame: Up to 5.5 years ]
    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.
16. Bone Scan Index (BSI) as Imaging Biomarker in metastatic castration-resistant prostate cancer (mCRPC) [ Time Frame: Up to 6 months ]
    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
17. Effect of concomitant drug treatment on pain, quality of life, and overall survival [ Time Frame: Up to 5.5 years ]
    Exploration of the influence of abiraterone, enzalutamide, opioids and denosumab on OS by number of injections (5-6 vs. 1-4)
18. Time from castration resistance to treatment with Radium-223 [ Time Frame: First treatment ]
    Time from verified castration resistance to first injection of Radium-223
19. Description of covariates on duration of therapy [ Time Frame: Up to 6 months ]
    Description of covariates on duration of therapy (to get ≥ 5 injections versus ≤ 4 injections) of mCRPC patients during treatment with Radium-223.
20. Factors positively influencing mCRPC patients to get ≥ 5 injections versus ≤ 4 injections [ Time Frame: Up to 6 months ]
    (e.g. concomitant use of antihormonal therapy, no pre-treatment of chemotherapy)
21. Incidence of pathological fractures, non-pathological fractures and bone associated events during treatment and follow up [ Time Frame: Up to 5.5 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No
• 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.

Criteria

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

Contacts and Locations

Locations

Germany

Multiple Locations, Germany

Sponsors and Collaborators

Bayer

Investigators

• Study Director: Bayer Study Director; Bayer

More Information

Additional Information:

Click here to find results for studies related to Bayer products 

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT02398526
• Other Study ID Numbers: 17550; XF1412DE ( Other Identifier: Company internal )
• First Posted: March 25, 2015
• Last Update Posted: November 2, 2021
• Last Verified: October 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bayer:

Observational study; Bone metastases; Hormone Refractory Prostatic Cancer; Xofigo; Radium-223

Additional relevant MeSH terms:

Neoplasm Metastasis; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Neoplastic Processes; Neoplasms; Pathologic Processes; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Prostatic Diseases; Radium Ra 223 dichloride; Antineoplastic Agents