Prostate CancerPhase 2NCT02199197
Radium Ra 223 With Enzalutamide Compared to Enzalutamide Alone in Men With Metastatic Castration Refractory Prostate Cancer
A Phase 2 study testing Radium Ra 223 Dichloride and Enzalutamide in people with Prostate Cancer, run by University of Utah at 1 site in United States.
Trial summary
Study of Radium Ra 223 dichloride with enzalutamide compared to enzalutamide alone in men with metastatic castration refractory prostate cancer Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Radium Ra 223 Dichloride and Enzalutamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Jun 2014to 3 Oct 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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).
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
About this study
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
Study of Radium Ra 223 dichloride with enzalutamide compared to enzalutamide alone in men with metastatic castration refractory prostate cancer
- Conditions
- Prostate Cancer
- Being tested
- Radium Ra 223 Dichloride, Enzalutamide
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radium Ra 223 DichlorideDrug
Also called Xofigo, Alpharadin
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.
EnzalutamideDrug
Also called Xtandi
Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
| Study group | Role | What they receive |
|---|---|---|
| Radium Ra 223 Dichloride and Enzalutamide | Experimental | Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Receives: Drug: Radium Ra 223 Dichloride; Drug: Enzalutamide |
| Enzalutamide alone | Active comparator | Enzalutamide administered as a single agent for 6 28-day cycles. Receives: Drug: Enzalutamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fold Change in Serum N-telopeptides From Baseline
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.
Measured: From prior to start of treatment to end of treatment or disease progression (approximately 6 months)
Number of Participants With Adverse Events
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.
Measured: From first dose of study treatment to 30 days following last dose (approximately 7 months)
Secondary outcomes (6)
Prostate Specific Antigen (PSA) Progression Free Survival (PFS)
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.
Measured: Up to 2 years (24 months)
Radiographic Progression Free Survival (PFS)
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.
Measured: Up to 2 years (24 months)
Bone Alkaline Phosphatase (ALP) Progression Free Survival (PFS)
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.
Measured: Up to 2 years (24 months)
Count of Prostate Specific Antigen (PSA) Responses
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
Measured: Up to 2 years after start of study treatment
Count of Radiographic Responses
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.
Measured: Up to 2 years after start of study treatment
Overall Survival (OS)
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.
Measured: Up to 40 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2014 (estimated)
- Study start25 Jun 2014
- Primary completion19 Apr 2018
- Study completion3 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02199197
- Sponsor's protocol ID
- HCI68770
- Status last verified
- Oct 2020
- First submitted
- 22 Apr 2014
- Last updated
- 30 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Agarwal N, Nussenzveig R, Hahn AW, Hoffman JM, Morton K, Gupta S, Batten J, Thorley J, Hawks J, Santos VS, Nachaegari G, Wang X, Boucher K, Haaland B, Maughan BL. Prospective Evaluation of Bone Metabolic Markers as Surrogate Markers of Response to Radium-223 Therapy in Metastatic Castration-resistant Prostate Cancer. Clin Cancer Res. 2020 May 1;26(9):2104-2110. doi: 10.1158/1078-0432.CCR-19-2591. Epub 2020 Jan 14.
PubMed 31937614
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02199197
- Acronym / sponsor ID
- HCI68770
- Conditions
- Prostate Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Study start
- 25 Jun 2014 (actual)
- Primary completion
- 19 Apr 2018 (actual)
- Study completion
- 3 Oct 2019 (actual)
- First posted
- 24 Jul 2014 (estimated)
- Results
- Posted 21 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study of Radium Ra 223 dichloride with enzalutamide compared to enzalutamide alone in men with metastatic castration refractory prostate cancer
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Radium Ra 223 Dichloride and Enzalutamide | Experimental | Drug: Radium Ra 223 Dichloride, Drug: EnzalutamideRadium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. |
| Enzalutamide alone | Active comparator | Drug: EnzalutamideEnzalutamide administered as a single agent for 6 28-day cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Radium Ra 223 DichlorideAlso: Xofigo, AlpharadinRadium 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. | Drug | Radium Ra 223 Dichloride and Enzalutamide |
| EnzalutamideAlso: XtandiEnzalutamide 160 mg administered orally once a day (continuously) for 6 cycles. | Drug | Enzalutamide alone, Radium Ra 223 Dichloride and Enzalutamide |
Primary outcome
Fold Change in Serum N-telopeptides From Baseline
Time frame: 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.
Number of Participants With Adverse Events
Time frame: 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.
6 secondary outcomes
Prostate Specific Antigen (PSA) Progression Free Survival (PFS)
Time frame: Up to 2 years (24 months)
Radiographic Progression Free Survival (PFS)
Time frame: Up to 2 years (24 months)
Bone Alkaline Phosphatase (ALP) Progression Free Survival (PFS)
Time frame: Up to 2 years (24 months)
Count of Prostate Specific Antigen (PSA) Responses
Time frame: Up to 2 years after start of study treatment
Count of Radiographic Responses
Time frame: Up to 2 years after start of study treatment
Overall Survival (OS)
Time frame: Up to 40 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31937614Agarwal N, Nussenzveig R, Hahn AW, Hoffman JM, Morton K, Gupta S, Batten J, Thorley J, Hawks J, Santos VS, Nachaegari G, Wang X, Boucher K, Haaland B, Maughan BL. Prospective Evaluation of Bone Metabolic Markers as Surrogate Markers of Response to Radium-223 Therapy in Metastatic Castration-resistant Prostate Cancer. Clin Cancer Res. 2020 May 1;26(9):2104-2110. doi: 10.1158/1078-0432.CCR-19-2591. Epub 2020 Jan 14.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Radium Ra 223 Dichloride and Enzalutamide in people with Prostate Cancer, run by University of Utah at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fold Change in Serum N-telopeptides From Baseline (time frame: From prior to start of treatment to end of treatment or disease progression (approximately 6 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02199197, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2020; AzTrials last refreshed its copy on 7 Nov 2026.