Open Label Phase Two Trial of Radium Ra 223 Dichloride With Concurrent Administration of Abiraterone Acetate Plus Prednisone in Symptomatic Castration-Resistant (Hormone-Refractory) Prostate Cancer Subjects With Bone Metastasis

NCT02097303 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CRP-PCA-01 eRADicAte
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Prostate Cancer

Keywords

Prostate Cancer; Bone Metastasis; Symptomatic; Androgen Independent; Hormone Refractory; Castrate Resistant; AIPC; pre-chemotherapy; Post-chemotherapy

Outcome Measures

Primary Outcomes (2)

• 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) 1. Pain Severity: Pain severity is the composite of scores of worst pain, least pain, average pain, and pain now. CMI criteria: Decrease \>30% at two consecutive visits in Pain Severity Score in 24 hours without an increase in analgesic use. 2. Pain interference: Pain interference is the composite scores on general activity, mood, walking ability, normal work, relationships with others, sleep and enjoyment of life. CMI criteria: Decrease by 1.25 points or more compared with baseline at two consecutive visits. 3. Transient Pain Flare: Based on the work of Atkinson et al, a transient pain flare was assessed by pain at its worst in 24 hours. CMI criteria: \> 2 points on the BPI-SF Worst Pain scale and subsequent reduction after initiation of Ra-223 and during the first 3 cycles.

  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 Outcomes (3)

• 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.

  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.

• Alkaline Phosphatase (ALP) and Prostate Specific Antigen (PSA) Levels Before and After Treatment

  Baseline and End of Treatment (EOT), approximately 32 weeks from Baseline

• Radiologic Assessment Mean Number of Bone Lesions Before and After the Treatment

  Baseline and End of Treatment (EOT), approximately 32 weeks from Baseline

Other Outcomes (2)

• Bone Imaging Response (Number of Participants With Progression and Stable Disease)

  Baseline and End of Treatment (EOT), approximately 32 weeks from Baseline

• Overall Response Rate

  Baseline and End of Treatment (EOT), approximately 32 weeks from Baseline

Study Arms (1)

Single arm

OTHER

All subjects receive concurrent administration of Radium Ra223 Dichloride and Abiraterone Acetate plus Prednisone

Drug: Concurrent use of Radium Ra 223 dichloride and Abiraterone Acetate plus Prednisone

Interventions

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.

Also known as: Xofigo, Zytiga

Single arm

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Subject has known malignant pleural effusion, or known lung, liver or brain metastasis (lymph node only metastasis \< 6 cm in short-axis diameter is allowed).
• Subject has a history of visceral metastatic disease as assessed by abdominal/pelvic CT or chest x-ray within the previous 8 weeks.
• Subject has received previous treatment with Abiraterone Acetate for longer than 90 days prior to enrollment, or any prior treatment with Radium Ra 223 dichloride.
• Subject has a known medical contraindication to Prednisone, Abiraterone Acetate or Radium Ra 223 dichloride.
• Subject is not willing to initiate a stable dose of daily Abiraterone Acetate plus Prednisone within 90 days of enrollment, or does not plan to initiate a stable daily dose of Abiraterone Acetate plus Prednisone within 30 days of the first Radium Ra 223 dichloride treatment.
• Subject does not plan to receive all 6 infusions of Radium Ra 223 Dichloride and daily Abiraterone Acetate plus Prednisone during the trial, per protocol.
• Subject has received previous strontium-89, samarium-153, rhenium-186, or rhenium-188 for the treatment of bone metastasis within 24 weeks prior to enrollment.
• Subject has received denosumab or Zolendronic Acid for less than 90 days prior to enrollment, or if the subject plans to discontinue an anti-resorptive medication prior to the EOT visit.
• Subject has received an investigational product or experimental therapy within 4 weeks of enrollment, or if initiation of either is planned prior to the EOT visit.
• Subject has a history of any medical condition that may be compromised by an increase in blood pressure, or severe liver insufficiency (r Child-Pugh class B or C).
• Subject has a history of a myocardial infarction or cardiac arrhythmia within 6 months prior to enrollment.
• Subject has a history of previous radiotherapy \>25% of bone marrow, including hemibody radiation.
• Subject has undergone major surgery within 4 weeks prior to enrollment.
• Subject has had a blood transfusion or erythropoietin stimulation agents within 4 weeks of enrollment.
• Subject has known imminent or established spinal cord compression.

Sponsors & Collaborators

• Carolina Research Professionals, LLC: lead
• Bayer: collaborator

Study Sites (5)

Chesapeake urology Research Associates

Towson, Maryland, 21204, United States

Location

Urology Cancer Center and GU Research Network

Omaha, Nebraska, 68130, United States

Location

Associated Medical Professionals

Syracuse, New York, 13210, United States

Location

Oregon Urology Institute

Springfield, Oregon, 97477, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Abiraterone Acetate; Prednisone; radium Ra 223 dichloride

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Results Point of Contact

• Title: Dr. Neal D. Shore, MD, FACS, CPI
• Organization: Carolina Research Professionals, LLC

nshore@carolinaresearchprofessionals.com

843-449-1010

Study Officials

• Neal D Shore, MD

  Carolina Research Professionals, LLC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2014
• First Posted: March 27, 2014
• Study Start: March 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: February 1, 2018
• Results First Posted: February 1, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)