Radium Ra 223 With Enzalutamide Compared to Enzalutamide Alone in Men With Metastatic Castration Refractory Prostate Cancer

Sponsor
University of Utah (Other)
Overall Status
Completed
CT.gov ID
NCT02199197
Collaborator
(none)
49
1
2
63.3
0.8

Study Details

Study Description

Brief Summary

Study of Radium Ra 223 dichloride with enzalutamide compared to enzalutamide alone in men with metastatic castration refractory prostate cancer

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
49 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Randomized Study Comparing Radium Ra 223 Dichloride Plus Enzalutamide With Enzalutamide Alone in Men With Metastatic Castration Refractory Prostate Cancer
Actual Study Start Date :
Jun 25, 2014
Actual Primary Completion Date :
Apr 19, 2018
Actual Study Completion Date :
Oct 3, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Radium Ra 223 Dichloride and Enzalutamide

Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles.

Drug: Radium Ra 223 Dichloride
Radium Ra 223 Dichloride, 55 kilobecquerel (kBq)/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles.
Other Names:
  • Xofigo
  • Alpharadin
  • Drug: Enzalutamide
    Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
    Other Names:
  • Xtandi
  • Active Comparator: Enzalutamide alone

    Enzalutamide administered as a single agent for 6 28-day cycles.

    Drug: Enzalutamide
    Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
    Other Names:
  • Xtandi
  • Outcome Measures

    Primary Outcome Measures

    1. Fold Change in Serum N-telopeptides From Baseline [From prior to start of treatment to end of treatment or disease progression (approximately 6 months)]

      Patients had serum N-telopeptide labs drawn prior to the start of treatment and at the End of Treatment visit or at disease progression, whichever occurred first. The mean and standard deviation of the differences were calculated on a log 2 scale. Fold changes (post/pre) and 95% confidence intervals are reported.

    2. Number of Participants With Adverse Events [From first dose of study treatment to 30 days following last dose (approximately 7 months)]

      Adverse Events were assessed from start of Radium Ra 223 Dichloride or Enzalutamide treatment (whichever was started first) through 30 days after the last dose of either drug or until start of a new anti-cancer therapy, whichever came first. Adverse events were assessed using the Common Terminology for Adverse Events (CTCAE) version 4.0. Each event was assigned a grade (1-5), with lower grades indicating milder events. All adverse events were recorded, regardless of attribution to study treatment. Reported below are the number of patients who experienced any grade 3-5 non-hematological AE. A full listing of AEs affecting 5% or more participants are listed in the Adverse Events module of the Results section.

    Secondary Outcome Measures

    1. Prostate Specific Antigen (PSA) Progression Free Survival (PFS) [Up to 2 years (24 months)]

      Prostate Specific Antigen (PSA) Progression Free Survival (PFS) is the time during with participants did not experience PSA progression. This is measured from the start of study therapy to the time of PSA progression. PSA progression is defined as a rise in PSA of at least 25% and at least 2 ng/ml from baseline or nadir. Kaplan-Meier methods were used.

    2. Radiographic Progression Free Survival (PFS) [Up to 2 years (24 months)]

      Radiographic Progression Free Survival (PFS) is the time during with participants did not experience disease progression based on study imaging. This is measured from the start of study therapy to the time of radiographic progression. Radiographic progression was defined by the Prostate Cancer Working Group 2 (PCWG2) criteria, in which soft tissue disease is evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and bone lesions are evaluated separately under PCWG2 criteria. PCWG2 and RECIST 1.1 are established radiographic assessment protocols. Kaplan-Meier methods were used.

    3. Bone Alkaline Phosphatase (ALP) Progression Free Survival (PFS) [Up to 2 years (24 months)]

      Bone Alkaline Phosphatase (ALP) Progression Free Survival (PFS) is the time during with participants did not experience Bone ALP progression. This is measured from the start of study therapy to the time of Bone ALP progression. Bone ALP progression defined as a rise in Bone ALP of at least 25% and at least 2 micrograms (mcg)/L from baseline or nadir. Kaplan-Meier methods were used.

    4. Count of Prostate Specific Antigen (PSA) Responses [Up to 2 years after start of study treatment]

      Prostate Specific Antigen (PSA) Responses in participants were categorized based on decrease from baseline: less than 30% (<30%) decrease (including increases from baseline), greater than or equal to 30% (>=30%) decrease, greater than or equal to 50% (>=50%) decrease, and greater than or equal to 90% (>=90%) decrease. Count of participants in each category are provided

    5. Count of Radiographic Responses [Up to 2 years after start of study treatment]

      Radiographic Responses in participants were assessed using the Prostate Cancer Working Group 2 (PCWG2) criteria. Possible responses include Complete Response (CR) (complete disappearance of all metastatic disease on imaging), Partial Response (PR) (improvement in metastatic disease on imaging), Stable Disease (SD) (neither worsening nor improvement of metastatic disease on imaging), and Progressive Disease (PD) (worsening of metastatic disease on imaging). A count of participants in each category is provided here.

    6. Overall Survival (OS) [Up to 40 months]

      Overall Survival (OS) is the time during which participants did not pass away. This is measured from the start of study therapy to the time of death from any cause. Kaplan-Meier methods were used.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Histologically documented adenocarcinoma of the prostate.

    • Men at least 18 years of age and life expectancy of greater than or equal to 6 months.

    • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.

    • Metastatic disease as evidenced by both lymphadenopathy and bony metastases or just bony metastases on baseline bone scan and/or computed tomography (CT) scan or MRI of the abdomen and pelvis within 28 days of registration. Chest imaging is only required if clinically indicated or if there is known disease in the chest.

    • Castration resistant prostatic adenocarcinoma. Subjects must have castrate levels of serum testosterone (less than 50 ng/dL) achieved by orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy.

    • Previously received docetaxel or are not healthy enough per clinical judgment or declined to receive it

    • Evidence of disease progression on or after the most recent systemic treatment defined by the following criteria:

    • Prostate-Specific Antigen (PSA): Increasing serum PSA levels as defined by the Prostate Cancer Working Group 2 (PCWG2), determined by 2 consecutive measurements (compared to a baseline or nadir value). If the third measurement is below the second, then a fourth measurement must be greater than the second. The confirming third or fourth measurement must be greater or equal to 2 ng/mL. PSA progression must have occurred within 15 months of registration (with at least 7 days between each PSA measurement). Additionally, the PSA progression as described above should have occurred during or after the most recent systemic treatment for prostate cancer.

    • Measurable disease: greater than or equal to 20% increase in the sum of the short axis diameter of all measurable lymph nodes or the development of any new measurable lymphadenopathy by RECIST 1.1 and PCWG2 criteria.

    • Non-measurable disease:

    • Lymph node disease: The appearance of 1 or more new lymphadenopathy, and/or unequivocal worsening of non-measurable disease when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response.

    • Bone disease: Appearance of 2 or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response. Increased uptake of pre-existing lesions on bone scan does not constitute progression.

    • Symptomatic bone metastases

    • Adequate hematologic, renal, and liver function as evidenced by laboratory test results. (Transfusion of blood products are not allowed to normalize blood parameters within 4 weeks of the first radium treatment.)

    • Subjects who have previously received docetaxel or are ineligible for docetaxel and who are candidates for treatment with enzalutamide alone or enzalutamide in combination with Radium-223

    • Men must agree to use adequate contraception beginning at the signing of the Informed Consent Form until at least 6 months after the last dose of study drug. Because of the potential side effect on spermatogenesis associated with radiation, men who are sexually active must agree to use condoms and their female partners of reproductive potential must agree to use a highly effective contraceptive method during and for 6 months after completing treatment.

    • Able to provide informed consent and have signed an approved consent form that conforms to federal and institutional guidelines to ensure compliance with HIPAA regulations.

    Exclusion Criteria:
    • The presence of known brain metastases, malignant pleural effusions, or malignant ascites. Brain MRI is required at screening only if clinically indicated.

    • Visceral metastases as assessed by chest, abdominal or pelvic computed tomography (CT) (or other imaging modality)

    • Received systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188, or Radium Ra 223 dichloride) for the treatment of bony metastases

    • Prior treatment with enzalutamide.

    • Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than the protocol based treatment. LHRH agonist or antagonist therapy, and supportive non-cancer directed therapies like bisphosphonates or denosumab are allowed.

    • Prior cytoxic chemotherapy with the exception of docetaxel or cabazitaxel. Treatment with docetaxel or cabazitaxel must be discontinued greater than 4 weeks from the time of enrollment, and recovery of adverse events (AEs) to grade 1 or baseline (however, ongoing neuropathy is permitted).

    • Major surgery within 30 days prior to start of study drug

    • Current, untreated pathologic long-bone fractures, imminent pathologic long-bone fractures (cortical erosion on radiography greater than 50%).

    • Prior hemi-body external radiotherapy. Subjects who received other types of prior external radiotherapy are allowed provided that bone marrow function is assessed and meets the protocol requirements for hemoglobin, absolute neutrophil count (ANC), and platelets.

    • Use of biologic response modifiers, such as granulocyte macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF) within 4 weeks prior to screening

    • Lymphadenopathy exceeding 3 cm in short-axis diameter

    • Any size pelvic lymphadenopathy if it is thought to be a contributor to concurrent hydronephrosis.

    • Current or imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Treatment should be completed for spinal cord compression.

    • Any other serious illness or medical condition in the opinion of the investigator, such as but not limited to:

    • Any greater than or equal to Grade 2 infection as defined by NCI-CTCAE version 4.03.

    • Cardiac failure New York Heart Association (NYHA) III or IV

    • Crohn's disease or ulcerative colitis

    • Bone marrow dysplasia

    • Fecal incontinence

    • Concomitant use of narrow therapeutic index drugs that are metabolized by CYP3A4 (i.e. alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus), CYP2C9 (phenytoin, warfarin), and CYP2C19 (S-mephenytoin). [Note: Patients on stable doses of anti-coagulation with warfarin and fentanyl will be eligible, as long as they are monitored closely with additional international normalized ratio (INR) monitoring].

    • Any infection requiring parenteral antibiotic therapy or causing fever (temperature greater than 100.5 degrees F or 38.1 degrees C) within 1 week prior to registration.

    • Concurrent other malignancy with the exception of: a) cutaneous squamous cell and basal carcinomas, b) adequately treated stage 1-2 malignancy , c) adequately treated stage 3-4 malignancy that had been in remission for greater than or equal to 2 years at the time of registration.

    • Inability to comply with the protocol and/or not willing or not available for follow-up assessments

    • Any medical intervention or other condition which, in the opinion of the Principal Investigator could compromise adherence with study requirements or otherwise compromise the study's objectives

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Huntsman Cancer Institute Salt Lake City Utah United States 84112

    Sponsors and Collaborators

    • University of Utah

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Utah
    ClinicalTrials.gov Identifier:
    NCT02199197
    Other Study ID Numbers:
    • HCI68770
    First Posted:
    Jul 24, 2014
    Last Update Posted:
    Oct 30, 2020
    Last Verified:
    Oct 1, 2020
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Radium Ra 223 Dichloride and Enzalutamide Enzalutamide Alone
    Arm/Group Description Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kilobecquerel (kBq)/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles. Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
    Period Title: Overall Study
    STARTED 35 14
    COMPLETED 35 12
    NOT COMPLETED 0 2

    Baseline Characteristics

    Arm/Group Title Radium Ra 223 Dichloride and Enzalutamide Enzalutamide Alone Total
    Arm/Group Description Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kBq/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles. Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles. Total of all reporting groups
    Overall Participants 35 14 49
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    11
    31.4%
    5
    35.7%
    16
    32.7%
    >=65 years
    24
    68.6%
    9
    64.3%
    33
    67.3%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    68.66
    (8.20)
    68.64
    (8.04)
    68.65
    (8.07)
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    69
    69.5
    69
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    Male
    35
    100%
    14
    100%
    49
    100%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    2.9%
    0
    0%
    1
    2%
    Not Hispanic or Latino
    34
    97.1%
    14
    100%
    48
    98%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    2.9%
    0
    0%
    1
    2%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    White
    34
    97.1%
    14
    100%
    48
    98%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Serum N-Telopeptide Levels (Log2 scale) (nM BCE) [Mean (Full Range) ]
    Mean (Full Range) [nM BCE]
    3.42
    3.41
    3.42

    Outcome Measures

    1. Primary Outcome
    Title Fold Change in Serum N-telopeptides From Baseline
    Description Patients had serum N-telopeptide labs drawn prior to the start of treatment and at the End of Treatment visit or at disease progression, whichever occurred first. The mean and standard deviation of the differences were calculated on a log 2 scale. Fold changes (post/pre) and 95% confidence intervals are reported.
    Time Frame From prior to start of treatment to end of treatment or disease progression (approximately 6 months)

    Outcome Measure Data

    Analysis Population Description
    Per study protocol, only randomized patients with bone marker level measurements at baseline and Cycle 3 Day 1 will be evaluable for the primary efficacy outcome. 8 patients were assigned to Radium + Enzalutamide without randomization and were excluded from analysis. 2 patients on Enzalutamide alone did not reach Cycle 3 Day 1 and were excluded.
    Arm/Group Title Radium Ra 223 Dichloride and Enzalutamide Enzalutamide Alone
    Arm/Group Description Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kBq/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles. Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
    Measure Participants 27 12
    Geometric Mean (95% Confidence Interval) [fold change]
    0.85
    1.34
    2. Primary Outcome
    Title Number of Participants With Adverse Events
    Description Adverse Events were assessed from start of Radium Ra 223 Dichloride or Enzalutamide treatment (whichever was started first) through 30 days after the last dose of either drug or until start of a new anti-cancer therapy, whichever came first. Adverse events were assessed using the Common Terminology for Adverse Events (CTCAE) version 4.0. Each event was assigned a grade (1-5), with lower grades indicating milder events. All adverse events were recorded, regardless of attribution to study treatment. Reported below are the number of patients who experienced any grade 3-5 non-hematological AE. A full listing of AEs affecting 5% or more participants are listed in the Adverse Events module of the Results section.
    Time Frame From first dose of study treatment to 30 days following last dose (approximately 7 months)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Radium Ra 223 Dichloride and Enzalutamide Enzalutamide Alone
    Arm/Group Description Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kBq/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles. Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
    Measure Participants 35 14
    Count of Participants [Participants]
    9
    25.7%
    2
    14.3%
    3. Secondary Outcome
    Title Prostate Specific Antigen (PSA) Progression Free Survival (PFS)
    Description Prostate Specific Antigen (PSA) Progression Free Survival (PFS) is the time during with participants did not experience PSA progression. This is measured from the start of study therapy to the time of PSA progression. PSA progression is defined as a rise in PSA of at least 25% and at least 2 ng/ml from baseline or nadir. Kaplan-Meier methods were used.
    Time Frame Up to 2 years (24 months)

    Outcome Measure Data

    Analysis Population Description
    Two participants who dropped out prior to Cycle 3 were excluded from analysis
    Arm/Group Title Radium Ra 223 Dichloride and Enzalutamide Enzalutamide Alone
    Arm/Group Description Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kilobecquerel (kBq)/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles. Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
    Measure Participants 35 12
    Median (95% Confidence Interval) [months]
    9.86
    3.34
    4. Secondary Outcome
    Title Radiographic Progression Free Survival (PFS)
    Description Radiographic Progression Free Survival (PFS) is the time during with participants did not experience disease progression based on study imaging. This is measured from the start of study therapy to the time of radiographic progression. Radiographic progression was defined by the Prostate Cancer Working Group 2 (PCWG2) criteria, in which soft tissue disease is evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and bone lesions are evaluated separately under PCWG2 criteria. PCWG2 and RECIST 1.1 are established radiographic assessment protocols. Kaplan-Meier methods were used.
    Time Frame Up to 2 years (24 months)

    Outcome Measure Data

    Analysis Population Description
    Two participants who dropped out prior to Cycle 3 were excluded from analysis
    Arm/Group Title Radium Ra 223 Dichloride and Enzalutamide Enzalutamide Alone
    Arm/Group Description Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kilobecquerel (kBq)/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles. Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
    Measure Participants 35 12
    Median (95% Confidence Interval) [months]
    11.31
    5.62
    5. Secondary Outcome
    Title Bone Alkaline Phosphatase (ALP) Progression Free Survival (PFS)
    Description Bone Alkaline Phosphatase (ALP) Progression Free Survival (PFS) is the time during with participants did not experience Bone ALP progression. This is measured from the start of study therapy to the time of Bone ALP progression. Bone ALP progression defined as a rise in Bone ALP of at least 25% and at least 2 micrograms (mcg)/L from baseline or nadir. Kaplan-Meier methods were used.
    Time Frame Up to 2 years (24 months)

    Outcome Measure Data

    Analysis Population Description
    Two participants who dropped out prior to Cycle 3 were excluded from analysis
    Arm/Group Title Radium Ra 223 Dichloride and Enzalutamide Enzalutamide Alone
    Arm/Group Description Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kilobecquerel (kBq)/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles. Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
    Measure Participants 35 12
    Median (95% Confidence Interval) [months]
    NA
    4.64
    6. Secondary Outcome
    Title Count of Prostate Specific Antigen (PSA) Responses
    Description Prostate Specific Antigen (PSA) Responses in participants were categorized based on decrease from baseline: less than 30% (<30%) decrease (including increases from baseline), greater than or equal to 30% (>=30%) decrease, greater than or equal to 50% (>=50%) decrease, and greater than or equal to 90% (>=90%) decrease. Count of participants in each category are provided
    Time Frame Up to 2 years after start of study treatment

    Outcome Measure Data

    Analysis Population Description
    Two participants who dropped out prior to Cycle 3 were excluded from analysis
    Arm/Group Title Radium Ra 223 Dichloride and Enzalutamide Enzalutamide Alone
    Arm/Group Description Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kilobecquerel (kBq)/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles. Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
    Measure Participants 35 12
    <30%
    6
    17.1%
    6
    42.9%
    >=30%
    5
    14.3%
    2
    14.3%
    >=50%
    9
    25.7%
    2
    14.3%
    >=90%
    15
    42.9%
    2
    14.3%
    7. Secondary Outcome
    Title Count of Radiographic Responses
    Description Radiographic Responses in participants were assessed using the Prostate Cancer Working Group 2 (PCWG2) criteria. Possible responses include Complete Response (CR) (complete disappearance of all metastatic disease on imaging), Partial Response (PR) (improvement in metastatic disease on imaging), Stable Disease (SD) (neither worsening nor improvement of metastatic disease on imaging), and Progressive Disease (PD) (worsening of metastatic disease on imaging). A count of participants in each category is provided here.
    Time Frame Up to 2 years after start of study treatment

    Outcome Measure Data

    Analysis Population Description
    Two participants who dropped out prior to Cycle 3 were excluded from analysis
    Arm/Group Title Radium Ra 223 Dichloride and Enzalutamide Enzalutamide Alone
    Arm/Group Description Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kilobecquerel (kBq)/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles. Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
    Measure Participants 35 12
    Complete Response (CR)
    0
    0%
    0
    0%
    Partial Response (PR)
    3
    8.6%
    0
    0%
    Stable Disease (SD)
    28
    80%
    8
    57.1%
    Progressive Disease (PD)
    4
    11.4%
    4
    28.6%
    8. Secondary Outcome
    Title Overall Survival (OS)
    Description Overall Survival (OS) is the time during which participants did not pass away. This is measured from the start of study therapy to the time of death from any cause. Kaplan-Meier methods were used.
    Time Frame Up to 40 months

    Outcome Measure Data

    Analysis Population Description
    Two participants who dropped out prior to Cycle 3 were excluded from analysis
    Arm/Group Title Radium Ra 223 Dichloride and Enzalutamide Enzalutamide Alone
    Arm/Group Description Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kilobecquerel (kBq)/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles. Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
    Measure Participants 35 12
    Median (95% Confidence Interval) [months]
    26.0
    21.0

    Adverse Events

    Time Frame The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months).
    Adverse Event Reporting Description The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
    Arm/Group Title Radium Ra 223 Dichloride and Enzalutamide Enzalutamide Alone
    Arm/Group Description Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kBq/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles. Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
    All Cause Mortality
    Radium Ra 223 Dichloride and Enzalutamide Enzalutamide Alone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 15/35 (42.9%) 8/14 (57.1%)
    Serious Adverse Events
    Radium Ra 223 Dichloride and Enzalutamide Enzalutamide Alone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/35 (20%) 2/14 (14.3%)
    Gastrointestinal disorders
    Gastrointestinal disorders - Other 1/35 (2.9%) 0/14 (0%)
    General disorders
    Pain 0/35 (0%) 1/14 (7.1%)
    Immune system disorders
    Anaphylaxis 1/35 (2.9%) 0/14 (0%)
    Infections and infestations
    Lung infection 1/35 (2.9%) 0/14 (0%)
    Urinary tract infection 1/35 (2.9%) 0/14 (0%)
    Investigations
    Neutrophil count decreased 1/35 (2.9%) 0/14 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 1/35 (2.9%) 0/14 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other 0/35 (0%) 1/14 (7.1%)
    Nervous system disorders
    Syncope 1/35 (2.9%) 0/14 (0%)
    Other (Not Including Serious) Adverse Events
    Radium Ra 223 Dichloride and Enzalutamide Enzalutamide Alone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 35/35 (100%) 12/14 (85.7%)
    Blood and lymphatic system disorders
    Anemia 9/35 (25.7%) 13 1/14 (7.1%) 13
    Cardiac disorders
    Palpitations 0/35 (0%) 1/14 (7.1%)
    Ear and labyrinth disorders
    Ear and labyrinth disorders - Other 2/35 (5.7%) 0/14 (0%)
    Vertigo 1/35 (2.9%) 1/14 (7.1%)
    Gastrointestinal disorders
    Abdominal pain 3/35 (8.6%) 2/14 (14.3%)
    Bloating 1/35 (2.9%) 1/14 (7.1%)
    Constipation 10/35 (28.6%) 0/14 (0%)
    Diarrhea 19/35 (54.3%) 25 1/14 (7.1%) 25
    Flatulence 1/35 (2.9%) 1/14 (7.1%)
    Gastroesophageal reflux disease 1/35 (2.9%) 1/14 (7.1%)
    Gastrointestinal disorders - Other 0/35 (0%) 1/14 (7.1%)
    Nausea 16/35 (45.7%) 23 1/14 (7.1%) 23
    Vomiting 4/35 (11.4%) 0/14 (0%)
    General disorders
    Chills 2/35 (5.7%) 3 1/14 (7.1%) 3
    Edema limbs 6/35 (17.1%) 7 0/14 (0%) 7
    Facial pain 0/35 (0%) 1/14 (7.1%)
    Fatigue 16/35 (45.7%) 20 3/14 (21.4%) 20
    Flu like symptoms 6/35 (17.1%) 0/14 (0%)
    Non-cardiac chest pain 2/35 (5.7%) 1/14 (7.1%)
    Infections and infestations
    Gum infection 2/35 (5.7%) 0/14 (0%)
    Investigations
    Alkaline phosphatase increased 1/35 (2.9%) 3/14 (21.4%) 4
    Blood bilirubin increased 0/35 (0%) 1/14 (7.1%)
    Creatinine increased 1/35 (2.9%) 2 1/14 (7.1%) 2
    Lymphocyte count decreased 18/35 (51.4%) 38 4/14 (28.6%) 6
    Neutrophil count decreased 14/35 (40%) 36 0/14 (0%) 36
    Platelet count decreased 7/35 (20%) 9 0/14 (0%) 9
    Weight loss 4/35 (11.4%) 0/14 (0%)
    White blood cell decreased 20/35 (57.1%) 47 0/14 (0%) 47
    Metabolism and nutrition disorders
    Anorexia 12/35 (34.3%) 0/14 (0%)
    Hypoalbuminemia 2/35 (5.7%) 1/14 (7.1%)
    Hypocalcemia 2/35 (5.7%) 0/14 (0%)
    Hypokalemia 2/35 (5.7%) 0/14 (0%)
    Hyponatremia 4/35 (11.4%) 0/14 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 7/35 (20%) 12 4/14 (28.6%) 5
    Back pain 7/35 (20%) 9 1/14 (7.1%) 9
    Bone pain 5/35 (14.3%) 2/14 (14.3%)
    Generalized muscle weakness 3/35 (8.6%) 1/14 (7.1%)
    Muscle weakness lower limb 0/35 (0%) 2/14 (14.3%)
    Muscle weakness upper limb 0/35 (0%) 1/14 (7.1%)
    Myalgia 8/35 (22.9%) 3/14 (21.4%) 6
    Neck pain 2/35 (5.7%) 0/14 (0%)
    Pain in extremity 4/35 (11.4%) 8 1/14 (7.1%) 8
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other 1/35 (2.9%) 1/14 (7.1%)
    Nervous system disorders
    Dizziness 4/35 (11.4%) 5 0/14 (0%) 5
    Dysgeusia 5/35 (14.3%) 1/14 (7.1%)
    Headache 5/35 (14.3%) 6 0/14 (0%) 6
    Paresthesia 4/35 (11.4%) 0/14 (0%)
    Peripheral sensory neuropathy 1/35 (2.9%) 1/14 (7.1%)
    Syncope 2/35 (5.7%) 0/14 (0%)
    Psychiatric disorders
    Anxiety 1/35 (2.9%) 1/14 (7.1%)
    Depression 1/35 (2.9%) 1/14 (7.1%)
    Insomnia 2/35 (5.7%) 0/14 (0%)
    Psychiatric disorders - Other 0/35 (0%) 1/14 (7.1%)
    Renal and urinary disorders
    Urinary frequency 2/35 (5.7%) 1/14 (7.1%)
    Urinary urgency 2/35 (5.7%) 0/14 (0%)
    Reproductive system and breast disorders
    Gynecomastia 0/35 (0%) 1/14 (7.1%)
    Testicular pain 2/35 (5.7%) 0/14 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 6/35 (17.1%) 1/14 (7.1%)
    Dyspnea 4/35 (11.4%) 1/14 (7.1%)
    Nasal congestion 3/35 (8.6%) 2/14 (14.3%)
    Pleural effusion 2/35 (5.7%) 0/14 (0%)
    Productive cough 1/35 (2.9%) 2/14 (14.3%) 3
    Sore throat 0/35 (0%) 1/14 (7.1%) 2
    Skin and subcutaneous tissue disorders
    Alopecia 0/35 (0%) 1/14 (7.1%)
    Pruritus 5/35 (14.3%) 0/14 (0%)
    Rash maculo-papular 2/35 (5.7%) 0/14 (0%)
    Skin and subcutaneous tissue disorders - Other 2/35 (5.7%) 0/14 (0%)
    Skin ulceration 0/35 (0%) 1/14 (7.1%)
    Vascular disorders
    Hot flashes 4/35 (11.4%) 5 0/14 (0%) 5
    Hypertension 3/35 (8.6%) 0/14 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Data Manager
    Organization Huntsman Cancer Institute Research Compliance Office
    Phone 801-585-0601
    Email compliance@hci.utah.edu
    Responsible Party:
    University of Utah
    ClinicalTrials.gov Identifier:
    NCT02199197
    Other Study ID Numbers:
    • HCI68770
    First Posted:
    Jul 24, 2014
    Last Update Posted:
    Oct 30, 2020
    Last Verified:
    Oct 1, 2020