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| Name | Class |
|---|---|
| Bayer | INDUSTRY |
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This is an open label study designed to examine the effects on concurrent administration of Radium Ra 223 dichloride and Abiraterone Acetate plus Prednisone in subjects with symptomatic castrate resistant prostate cancer and with bone metastases, in both the pre- and post- chemotherapy setting. Both medications are approved by the US Food and Drug Administration for this indication.
Approximately 40 subjects will be enrolled to obtain 30 evaluable subjects. All subjects will receive Radium Ra 223 dichloride every 4 weeks for a total of 6 doses over 24 weeks and concurrent Abiraterone Acetate plus Prednisone for a minimum duration of 26 weeks.
Subjects will be evaluated 30 days after the last dose of Radium Ra 223 dichloride. All adverse events deemed to be study related will be followed until resolution. Including screening, the total duration of the study is 32 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single arm | Other | All subjects receive concurrent administration of Radium Ra223 Dichloride and Abiraterone Acetate plus Prednisone |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Concurrent use of Radium Ra 223 dichloride and Abiraterone Acetate plus Prednisone | Drug | Radium Ra 223 dichloride - A targeted alpha particle-emitting pharmaceutical (a radiopharmaceutical drug) is a ready-to-use solution for intravenous injection containing the drug substance radium dichloride. The active moiety is the alpha particle emitting nuclide Ra-223, present as a divalent cation (223Ra2+) and Abiraterone Acetate - A CYP17 inhibitor, indicated in combination with prednisone for the treatment of subjects with metastatic castration-resistant prostate cancer. Administration of Abiraterone Acetate may result in mineralocorticoid-related adverse events (AEs), due to CYP17 inhibition. Therefore, Abiraterone Acetate is administered in combination with Prednisone to reduce the frequency of these AEs. |
| Measure | Description | Time Frame |
|---|---|---|
| Number and Percentage of Participants With Clinically Meaningful Improvement (Between Baseline and End of Treatment) in Quality-of-Life Determined by the Minimum Increase From Baseline in Scores as Per the QOL CMI Criteria | Following Quality of Life questionnaires were given at each visit: FACT-P assesses symptoms/problems related to prostate carcinoma and its treatment. It is a combination of the FACT- General + the PCS (Range 1-156, higher scores better). The FACT-General (FACT-G) is a 28 item QOL measure that provides a total score as well as subscale scores: Physical (0-28), Functional (0-28), Social (0-28), Emotional (0-24) Well-being, and Satisfaction with Treatment was not assessed for this study (The total range was between 1-108, higher scores better) FACT-TOI is derived from the sum of the Physical Well-Being, Functional Well-Being, and Prostate Cancer subscale scores; a sensitive measure of patient-reported health (Range 1-104, higher scores better) PCS is a 12-item prostate cancer subscale that asks about symptoms and problems specific to prostate cancer (Range 0-48, higher scores better). | Subjects were evaluated at the screening visit, monthly during the study, and 30 days after the last dose of Radium Ra 223 dichloride, which will be approximately 32 weeks after the screening visit of evaluable subjects. |
| Number and Percentage of Participants With Clinically Meaningful Improvement (CMI) in Pain (Between Baseline and End of Treatment) | Improvement in Bone Pain was assessed using the Bone Pain Inventory (BPI)
| Subjects were evaluated at the screening visit, monthly during the study, and 30 days after the last dose of Radium Ra 223 dichloride, which will be approximately 32 weeks after the screening visit of evaluable subjects. |
| Measure | Description | Time Frame |
|---|---|---|
| Safety Data Was Analyzed and Summarized in Subjects Who Receive at Least One Infusion of Radium Ra 223 Dichloride. Number of Adverse Events Are Being Reported. | All adverse events relevant to advanced mCRPC subjects as well as adverse events of interest for both Abiraterone Acetate plus Prednisone and Radium Ra 223 dichloride will be reported. | Subjects were evaluated at the screening visit, monthly during the study, and 30 days after the last dose of Radium Ra 223 dichloride, which will be approximately 32 weeks after the screening visit of evaluable subjects. |
| Measure | Description | Time Frame |
|---|---|---|
| Bone Imaging Response (Number of Participants With Progression and Stable Disease) | Bone imaging response was assessed at baseline and at EOT visit. Progression was defined as two or more additional lesions in comparison to the baseline. | Baseline and End of Treatment (EOT), approximately 32 weeks from Baseline |
| Overall Response Rate |
Inclusion Criteria:
Eligible subjects will conform to all of the inclusion criteria listed below:
Subject must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.
Subject is willing and able to comply with the protocol, including all study visits and procedures.
Subject is a male, greater than 18 years at time of enrollment.
Life expectancy of at least 9 months.
Subject has histologically documented prostate cancer confirmed by a pathology report from a prostate biopsy or radical prostatectomy specimen.
Subject must:
• have initiated a stable dose of daily Abiraterone Acetate plus Prednisone within 90 days of enrollment, or
• plans to initiate a stable daily dose of Abiraterone plus Prednisone within 30 days of the first Radium Ra 223 dichloride treatment.
Subject must plan to receive all 6 Radium Ra 223 dichloride injections and daily oral doses of Abiraterone plus Prednisone during the trial, per protocol.
Subject has a history of bone metastasis from prostate cancer as evidenced by imaging performed within 90 days of enrollment from one of the following:
• Tc Bone Scan or
• Sodium Fluoride PET/CT Scan
*If a bone scan is used, solitary lesions which could be contributed to causes other than prostate cancer must be confirmed with a second modality (i.e.: plain films, CT Scan or MRI.
Subject has Castrate Resistant Prostate Cancer, defined as rising PSA with a testosterone level </= 50ng/dl (2.0 nM/L) while receiving androgen deprivation therapy (medical or surgical castration).
* PSA progression will be defined as at least 2 rising PSA levels taken at least 7 days apart with the 2nd PSA being 2.0 ng/dl or greater.
Subject has the presence of bone pain requiring treatment with:
1) EBRT within the previous 12 weeks prior to enrollment, or 2) Analgesic medications (including but not limited to acetaminophen, NSAIDS, Cox-2 inhibitors, and narcotic Opioids).
11. Subject has an ECOG performance status of 0-2 at screening 12. Acceptable hematology and serum biochemistry screening values:
• White Blood Cell (WBC) >/= 3,000/mm3
Absolute Neutrophil Count (ANC) >1500/mm3
Platelet (PLT) count >100,000/mm3
Hemoglobin (HGB) > 10.0 g/dL (100g/L; 6.2 mmol/L
Creatinine <1.5 ULN
Total bilirubin level <1.5 X ULN
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 X ULN
albumin >25 g/L
Baseline electrolytes within normal limits ( Sodium, potassium, chloride, calcium, phosphate, magnesium, LDH, γGT, urea, total protein) 13. Normal Liver Function Tests (LFT) and normal Renal Function Tests (RFT) at screening visit. If the subject has LFT's or RFT's greater than 2.5 times the upper limit of normal (ULN), Medical Monitor review, in conjunction with the subject's PI, will be required.
14. Subjects receiving Anti-Resorptive medications (such as Zolendronic Acid or denosumab) must be on a stable dose for at least 90 days prior to enrollment (Cycle 1/Week 1/ Day 1). Anti-resorptive medications may be added to the subject's regimen after the End of Treatment visit has been completed. Anti-resorptive medication withdrawal will be allowed per Investigator discretion due to adverse events attributable to that medication.
15. Subjects of childbearing potential must agree to use adequate contraception beginning at the enrollment until at least 30 days after the last dose of the study drugs. The definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate.
Exclusion Criteria:
Eligible subjects must not meet any of the exclusion criteria listed below:
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| Name | Affiliation | Role |
|---|---|---|
| Neal D Shore, MD | Carolina Research Professionals, LLC | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chesapeake urology Research Associates | Towson | Maryland | 21204 | United States | ||
| Urology Cancer Center and GU Research Network |
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| ID | Title | Description |
|---|---|---|
| FG000 | Radium 223 With Concomitant Abiraterone Acetate and Prednisone | Name of active ingredient Radium Ra 223 dichloride Dose 50 kBq/kg body weight Route of Administration Intravenous Duration of Treatment One injection every 4 weeks X 6 injections maximum. Name of active ingredient Abiraterone Acetate plus Prednisone Dose 1000 mg/day and 5 mg BID Route of Administration Oral Duration of Treatment 26 weeks minimum duration. There is no maximum duration. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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|
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| Alkaline Phosphatase (ALP) and Prostate Specific Antigen (PSA) Levels Before and After Treatment | [Not specified] | Baseline and End of Treatment (EOT), approximately 32 weeks from Baseline |
| Radiologic Assessment Mean Number of Bone Lesions Before and After the Treatment | [Not Specified] | Baseline and End of Treatment (EOT), approximately 32 weeks from Baseline |
Determination of measurable disease progression or response was based on modified RECIST criteria. Reported is the number of participants with either a partial or complete response, and who had radiological extraskeletal progression. |
| Baseline and End of Treatment (EOT), approximately 32 weeks from Baseline |
| Omaha |
| Nebraska |
| 68130 |
| United States |
| Associated Medical Professionals | Syracuse | New York | 13210 | United States |
| Oregon Urology Institute | Springfield | Oregon | 97477 | United States |
| Carolina Urologic Research Center | Myrtle Beach | South Carolina | 29572 | United States |
| COMPLETED |
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| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Radium 223 With Concomitant Abiraterone Acetate and Prednisone | Name of active ingredient Radium Ra 223 dichloride Dose 50 kBq/kg body weight Route of Administration Intravenous Duration of Treatment One injection every 4 weeks X 6 injections maximum. Name of active ingredient Abiraterone Acetate plus Prednisone Dose 1000 mg/day and 5 mg BID Route of Administration Oral Duration of Treatment 26 weeks minimum duration. There is no maximum duration. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| ||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| |||||||||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number and Percentage of Participants With Clinically Meaningful Improvement (Between Baseline and End of Treatment) in Quality-of-Life Determined by the Minimum Increase From Baseline in Scores as Per the QOL CMI Criteria | Following Quality of Life questionnaires were given at each visit: FACT-P assesses symptoms/problems related to prostate carcinoma and its treatment. It is a combination of the FACT- General + the PCS (Range 1-156, higher scores better). The FACT-General (FACT-G) is a 28 item QOL measure that provides a total score as well as subscale scores: Physical (0-28), Functional (0-28), Social (0-28), Emotional (0-24) Well-being, and Satisfaction with Treatment was not assessed for this study (The total range was between 1-108, higher scores better) FACT-TOI is derived from the sum of the Physical Well-Being, Functional Well-Being, and Prostate Cancer subscale scores; a sensitive measure of patient-reported health (Range 1-104, higher scores better) PCS is a 12-item prostate cancer subscale that asks about symptoms and problems specific to prostate cancer (Range 0-48, higher scores better). | Improvement at the EOT visit was defined as increase from baseline of >= 10 points for FACT-P Total Scale. >9 points for FACT-G Total and FACT-TOI scales, and >=3 points for the remaining scales. | Posted | Count of Participants | Participants | Subjects were evaluated at the screening visit, monthly during the study, and 30 days after the last dose of Radium Ra 223 dichloride, which will be approximately 32 weeks after the screening visit of evaluable subjects. |
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| Secondary | Safety Data Was Analyzed and Summarized in Subjects Who Receive at Least One Infusion of Radium Ra 223 Dichloride. Number of Adverse Events Are Being Reported. | All adverse events relevant to advanced mCRPC subjects as well as adverse events of interest for both Abiraterone Acetate plus Prednisone and Radium Ra 223 dichloride will be reported. | Posted | Number | Adverse Events | Subjects were evaluated at the screening visit, monthly during the study, and 30 days after the last dose of Radium Ra 223 dichloride, which will be approximately 32 weeks after the screening visit of evaluable subjects. |
|
| ||||||||||||||||||||||||||||||||||||||
| Secondary | Alkaline Phosphatase (ALP) and Prostate Specific Antigen (PSA) Levels Before and After Treatment | [Not specified] | Posted | Mean | Standard Deviation | ng/dL | Baseline and End of Treatment (EOT), approximately 32 weeks from Baseline |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Radiologic Assessment Mean Number of Bone Lesions Before and After the Treatment | [Not Specified] | Posted | Mean | Standard Deviation | Lesions | Baseline and End of Treatment (EOT), approximately 32 weeks from Baseline |
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| Other Pre-specified | Bone Imaging Response (Number of Participants With Progression and Stable Disease) | Bone imaging response was assessed at baseline and at EOT visit. Progression was defined as two or more additional lesions in comparison to the baseline. | Posted | Count of Participants | Participants | Baseline and End of Treatment (EOT), approximately 32 weeks from Baseline |
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| Primary | Number and Percentage of Participants With Clinically Meaningful Improvement (CMI) in Pain (Between Baseline and End of Treatment) | Improvement in Bone Pain was assessed using the Bone Pain Inventory (BPI)
| Posted | Count of Participants | Participants | Subjects were evaluated at the screening visit, monthly during the study, and 30 days after the last dose of Radium Ra 223 dichloride, which will be approximately 32 weeks after the screening visit of evaluable subjects. |
| |||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Overall Response Rate | Determination of measurable disease progression or response was based on modified RECIST criteria. Reported is the number of participants with either a partial or complete response, and who had radiological extraskeletal progression. | Posted | Count of Participants | Participants | Baseline and End of Treatment (EOT), approximately 32 weeks from Baseline |
|
|
Adverse events were collected from enrollment through 6 monthly cycles, and 30 days after the end of treatment, for a total of 7 months.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Radium 223 With Concomitant Abiraterone Acetate and Prednisone | Name of active ingredient Radium Ra 223 dichloride Dose 50 kBq/kg body weight Route of Administration Intravenous Duration of Treatment One injection every 4 weeks X 6 injections maximum. Name of active ingredient Abiraterone Acetate plus Prednisone Dose 1000 mg/day and 5 mg BID Route of Administration Oral Duration of Treatment 26 weeks minimum duration. There is no maximum duration. | 1 | 36 | 5 | 36 | 30 | 36 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Pain | Gastrointestinal disorders | Non-systematic Assessment | Deemed treatment related. |
| |
| Cardiopulmonary Arrest | Cardiac disorders | Non-systematic Assessment |
| ||
| Urinary Tract Infection | Infections and infestations | Non-systematic Assessment |
| ||
| Syncope | Cardiac disorders | Systematic Assessment |
| ||
| Small Bowel Obstruction | Gastrointestinal disorders | Systematic Assessment |
| ||
| Congestive Heart Failure | Cardiac disorders | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | Non-systematic Assessment |
| ||
| Leukopenia | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Pancytopenia | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
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| Stomach Pain | Gastrointestinal disorders | Non-systematic Assessment |
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| Abdominal Pain | Gastrointestinal disorders | Non-systematic Assessment |
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| Decreased Appetitie | Gastrointestinal disorders | Non-systematic Assessment |
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| Dysguesia | Gastrointestinal disorders | Non-systematic Assessment |
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| Edema Limbs | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Fatigue | Endocrine disorders | Non-systematic Assessment |
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| Increased Liver Function Tests | Hepatobiliary disorders | Non-systematic Assessment |
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| Decreased Red Blood Count | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Increased ALT | Hepatobiliary disorders | Non-systematic Assessment |
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| Increased ALT | Hepatobiliary disorders | Non-systematic Assessment |
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| Increased ALP | Hepatobiliary disorders | Non-systematic Assessment |
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| Hypocalcemia | Investigations | Non-systematic Assessment |
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| Hyponatremia | Investigations | Non-systematic Assessment |
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| Hyponatremia | Investigations | Non-systematic Assessment |
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| Hypochloremia | Investigations | Non-systematic Assessment |
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| Bone Pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| Myalgia | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Dizziness | Ear and labyrinth disorders | Non-systematic Assessment |
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| Headaches | Ear and labyrinth disorders | Non-systematic Assessment |
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| Paresthesia | Ear and labyrinth disorders | Non-systematic Assessment |
| ||
| Gynecomastia | Reproductive system and breast disorders | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Neal D. Shore, MD, FACS, CPI | Carolina Research Professionals, LLC | 843-449-1010 | 243 | nshore@carolinaresearchprofessionals.com |
| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| D000069501 | Abiraterone Acetate |
| D011241 | Prednisone |
| C581106 | radium Ra 223 dichloride |
| ID | Term |
|---|---|
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D011244 | Pregnadienediols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
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| African American |
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| Title | Measurements |
|---|---|
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| Prostate Cancer Subscale (PCS) |
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| Physical Well-being |
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| Functional Well-being |
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| Emotional Well-being |
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| Social Well-being |
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