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Castration-resistant Prostate CancerPhase 2DICENCT03869762

Denosumab in Combination With Enzalutamide in Progressive Metastatic Castrate-resistant Prostate Cancer and Bone Metastases.

A Phase 2 study testing Xgeva and Xtandi in people with Castration-resistant Prostate Cancer and Metastatic Cancer, run by Cancer Trials Ireland at 7 sites in Ireland.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

Open-label phase II multi-centre single arm study of Denosumab in combination with enzalutamide in progressive metastatic castrate-resistant prostate cancer. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Xgeva and Xtandi
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
7 sitesIreland
Study dates
9 Jan 2019to 12 Jan 2019
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Written informed consent obtained prior to any study-related procedures.
  • Age ≥ 18 years and male.
  • ECOG performance status ≤ 2.
  • Histologically/cytologically confirmed adenocarcinoma of the prostate, and without neuroendocrine differentiation or small cell histology.
  • Documented metastatic disease with at least 1 bone metastasis on bone scan and confirmed, if necessary, by CT scan or MRI, if results of the bone scans are ambiguous. Patients with or without visceral involvement / lymph nodes (documented by RECIST 1.1) are allowed.
  • Patients must have documented Progressive disease (PD) either by radiographic or PSA criteria as defined in a) and b) below:
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  • For the Radiographic PD assessment, 2 sets of scans using the same imaging modality (ie CT/MRI or bone scan) and taken at separate time points are required to document radiographic disease progression during or following the patient's most recent anti-neoplastic therapy, (note: the 1st bone scan can be from before most recent therapy but the 2nd scan must show disease progression during or after the most recent therapy).
  • For patients with bone disease, progression will be assessed following recommendations by the Prostate Cancer Working Group (PCWG3) (Appendix I): appearance of 2 or more new lesions on bone scan, confirmed, if necessary, by other imaging modalities (such as CT scan or MRI), if results of the bone scans are ambiguous).
  • For patients with soft tissue lesions progression will be assessed using RECIST 1.1 criteria, (see Appendix C). Patients may have measurable or non-measurable disease according to RECIST criteria version 1.1 (see Appendix C)
  • PSA progression as per PCWG3 (Appendix I) is defined as an increase in PSA, as determined by 2 separate measurements taken at least 1 week apart and confirmed by a third. If the third measurement is not greater than the second measurement, then a fourth measurement must be taken and must be greater than the second measurement for the patient to be eligible for the study. Furthermore, the confirmatory PSA measurement (i.e. the third or, if applicable, fourth PSA measurement) must be defined. If a patient has received prior anti-androgen therapy (e.g. bicalutamide), PSA progression must be evident and documented after discontinuation of anti-androgen therapy, (note: The 1st PSA reading taken to document disease progression when the patient presents can be while the patient is on Casodex or other ADT).
  • Prior surgical castration or concurrent use of an agent for medical castration (e.g. GnRH analogue) with testosterone at screening less than 1.73 nmol /l (50ng/dL).
  • Screening PSA ≥ 2 ng/mL.
  • Patients must agree to:
  • abstain from intercourse or
  • if the patient engages in sexual intercourse with a woman of childbearing potential, a condom and a highly effective birth control must be used (i.e. hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion or a vasectomy that has received medical assessment of the surgical success) during treatment and for 5 months after treatment.
  • Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 28 days prior to registration.
  • Life expectancy of 12 months or more based on general health and prostate cancer disease status as judged by the investigator.
  • Able to swallow study drug as whole tablet.
  • Adequate haematological, hepatic, and renal function.
  • Haemoglobin ≥ 10g/dL.
  • Neutrophils (ANC/AGC) ≥ 1500/mm³ (1.5 x 109/L).
  • Platelets ≥ (100 x 109/L).
  • Total bilirubin ≤ 1.5mg/dL (25.65 μmol/L) with the exception of Gilberts syndrome.
  • Both Alanine aminotransferase (ALT (SGPT)) and Aspartate aminotransferase (AST (SGOT) ≤ 3 x ULN with or without liver Metastasis.
  • Calculated creatinine clearance (CrCl) ≥ 30mL/min according to the Cockcroft and Gault formula (Appendix D).
  • Serum corrected Calcium within normal range and > 2 mmol/L
  • Continuous daily use of oral prednisone, oral dexamethasone, or other systemic corticosteroids is allowed prior to study entry but must be discontinued a minimum of 2 weeks prior to start of study treatment.

Who cannot join

  • Patients should not be receiving any other investigational agents for the treatment of prostate cancer or other diseases (within 30 days prior to registration).
  • Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis).
  • Have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment).
  • Prior therapy with orteronel, ketoconazole, aminoglutethimide, abiraterone or enzalutamide, denosumab or radium 223.
  • All anti-androgen therapy (including bicalutamide) is excluded within 6 weeks prior to first dose of study drug. Any other therapies for prostate cancer, other than GnRH analogue therapy, such as progesterone, medroxyprogesterone, progestins (megesterol), or 5-alpha reductase inhibitors (eg, finasteride or dutasteride), must be discontinued 2 weeks before the first dose of study drug. No prior bisphosphonates/Rank ligand inhibitors are allowed except when administered for bone density preservation in association with androgen deprivation therapy.
  • Prior chemotherapy for prostate cancer, with the exception of:
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  • neoadjuvant/ adjuvant therapy as part of initial primary treatment for local disease that was completed 2 or more years prior to screening.
  • Patients who received prior docetaxol for castrate sensitive metastatic prostate cancer commencing with 120 days of ADT initation where total dose received did not exceed 450mg/m2
  • Diagnosis of or treatment for another systemic malignancy within 2 years before the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
  • History of myocardial infarction, unstable symptomatic ischemic heart disease/ unstable angina, uncontrolled on-going arrhythmias of Grade >2 (National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5), pulmonary embolism, or any other cardiac condition (e.g. pericardial effusion restrictive cardiomyopathy) within 6 months prior to first dose of study drug. Patients with long QT, QTcF >470ms or uncontrolled hypertension are excluded.
  • New York Heart Association Class III or IV heart failure (see Appendix F).
  • History of seizure, underlying brain injury with loss of consciousness, stroke, transient ischaemic attack (TIA), cerebral vascular accident, primary brain tumours or brain metastases, brain arteriovenous malformation, alcoholism, or the use of concomitant medications that may lower the seizure threshold.
  • Known human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C, life-threatening illness unrelated to cancer, or any ongoing serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with participation in this study. Patients will be tested for hepatitis B or C or HIV infection during screening if they are considered by the investigator to be at higher risk for these infections and have not been previously tested, or if testing is required by the independent ethics committee or institutional review board.
  • Prohibited medications, including drugs that are known to lower the seizure threshold or prolong QT interval are not permitted see section 7.4.2.
  • Patients with prior history of ONJ or osteomyelitis of the jaw, an active dental or jaw condition requiring oral surgery, non-healed dental/oral surgery, or any planned invasive dental procedure are excluded as confirmed by dental examination.
  • Patients with rare hereditary problems of fructose intolerance.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Ireland7 sites

  • Cork University Hospital

    Cork, Munster

  • Adelaide and Meath incorporating National Children's Hopsital

    Dublin, Leinster

  • St. Vincent's Hospital

    Dublin, Leinster

  • Galway University Hospital

    Galway, Connacht

  • University Hospital Limerick

    Limerick, Munster

  • Sligo University Hospital

    Sligo, Connacht

  • University Hospital Waterford

    Waterford, Munster

Other trials in Ireland

About this study

Official title: A Phase II Study of Denosumab in Combination With Enzalutamide in Progressive Metastatic Castrate-resistant Prostate Cancer and Bone Metastases.

Open-label phase II multi-centre single arm study of Denosumab in combination with enzalutamide in progressive metastatic castrate-resistant prostate cancer.

Read the detailed description

This is an open-label phase II multi-centre single arm study of Denosumab in combination with enzalutamide in progressive metastatic castrate-resistant prostate cancer.

Being tested
Xgeva, Xtandi
Keywords
Castration-resistant, Progressive, Metastatic, Prostate Cancer, Bone Metastases
Medical subject headings
Neoplasm Metastasis, Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • XgevaDrug

    Also called Denosumab

    Denosumab is a human monoclonal antibody (IgG2) that targets and binds with high affinity and specificity to RANKL, preventing the RANKL/RANK interaction from occurring and resulting in reduced osteoclast numbers and function, thereby decreasing bone resorption and cancer induced bone destruction.

  • XtandiDrug

    Also called Enzalutamide

    Enzalutamide is a potent androgen receptor signalling inhibitor that blocks several steps in the androgen receptor signalling pathway. Enzalutamide competitively inhibits binding of androgens to androgen receptors, inhibits nuclear translocation of activated receptors and inhibits the association of the activated androgen receptor with DNA even in the setting of androgen receptor overexpression and in prostate cancer cells resistant to anti-androgens.

    Enzalutamide treatment decreases the growth of prostate cancer cells and can induce cancer cell death and tumour regression.

Study groups in NCT03869762
Study groupRoleWhat they receive
Denosumab & EnzalutamideExperimental120mg subcutaneous injection on Day 1 of every four week cycle, for a maximum of 24 cycles, or until clinical disease progression, unacceptable toxicity, consent withdrawal or withdrawal for any other reason. 160mg PO daily; (4 x 40 mg capsules) until confirmed clinical disease progression, unacceptable toxicity, consent withdrawal or withdrawal for any other reason)
Receives: Drug: Xgeva; Drug: Xtandi

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Radiographic progression free survival (rPFS)

    Measured according to PCWG3 and RECIST 1.1 criteria. Result will be compared to historical rPFS in Enzalutamide be compared to historical rPFS in Enzalutamide

    Measured: 12 months

Secondary outcomes (4)

  1. Overall survival

    Result will be compared to historical OS in Enzalutamide Enzalutamide

    Measured: 24 months

  2. PSA progression free survival

    Measured according to the PCWG3 criteria

    Measured: 24 months

  3. Time to first skeletal-related event

    Event will be calculated from the date of registration to the date of first skeletal-related event

    Measured: 24 months

  4. Pain assessment

    Brief Pain Inventory - Short Form

    Measured: 24 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Mar 2019
  2. Study start9 Jan 2019
  3. Primary completion12 Jan 2019
  4. Study completion12 Jan 2019

Why it stopped: Insufficient accrual

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03869762
Sponsor's protocol ID
CTRIAL-IE 17-17
Acronym
DICE
Status last verified
Apr 2026
First submitted
8 Mar 2019
Last updated
13 Apr 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Xgeva and Xtandi in people with Castration-resistant Prostate Cancer and Metastatic Cancer, run by Cancer Trials Ireland at 7 sites in Ireland.

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 27 inclusion and 16 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: stopped early, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Ireland. 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?

The study was stopped early (reason given: Insufficient accrual). Results are not available in the source record.

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?

Radiographic progression free survival (rPFS) (time frame: 12 months). 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 NCT03869762.

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 13 Apr 2026.

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