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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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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
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

Other trials in United States

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 groups in NCT02199197
Study groupRoleWhat they receive
Radium Ra 223 Dichloride and EnzalutamideExperimentalRadium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles.
Receives: Drug: Radium Ra 223 Dichloride; Drug: Enzalutamide
Enzalutamide aloneActive comparatorEnzalutamide 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.

  1. 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)

  2. 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)

  1. 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)

  2. 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)

  3. 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)

  4. 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

  5. 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

  6. 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.

  1. First posted24 Jul 2014 (estimated)
  2. Study start25 Jun 2014
  3. Primary completion19 Apr 2018
  4. Study completion3 Oct 2019

Resources

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)
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
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

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.

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