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Bone Metastatic Castration-Resistant Prostate CancerEarly Phase 1NCT02204943

Pharmacodynamic Study of Radium-223 in Men With Bone Metastatic Castration-Resistant Prostate Cancer

A Early Phase 1 study testing Biomarker analysis and Administration of radium-223 in people with Bone Metastatic Castration-Resistant Prostate Cancer, run by Duke University 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

This study will examine biomarkers involved in osteomimicry in bone metastases and circulating tumor cells (CTCs) of men with mCRPC before and during therapy with the bone-targeting radiopharmaceutical radium-223. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Biomarker analysis and Administration of radium-223
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
6 May 2015to 31 Jul 2017
Phase
Early Phase 1
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

  • Age ≥ 18 years.
  • Life expectancy of at least 12 weeks (3 months).
  • Subjects must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.
  • Histologically confirmed diagnosis of adenocarcinoma of the prostate. Histologic variants of prostate cancer, including neuroendocrine features are permitted; however, pure small cell carcinoma of the prostate is excluded.
  • Presence of >2 sites of metastatic disease in bone as determined by bone scan or CT, and for men who opt-in for bone biopsy, they must have at least one site amenable to radiographically-guided metastatic biopsy as determined by the study radiologist.
  • Symptomatic castration-resistant bone metastatic disease as determined by the provider.
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  • Prior or concurrent therapy with either abiraterone acetate or enzalutamide.
  • Ongoing ADT using an LHRH agonist (e.g. leuprolide, goserelin) or antagonist (e.g. degarelix) must continue on therapy unless prior bilateral orchiectomy has been performed.
  • Current evidence of disease progression as evidenced by one of the following:
  • 2 consecutive rising PSA levels separated at least 1 week apart above nadir PSA on last systemic therapy. If no nadir, then 2 rising PSA values greater than baseline pretreatment value is required from the most immediate prior therapy, OR
  • CT or bone scan based evidence of disease progression with bone metastasis (new lesions or growth of existing lesions), OR
  • Evidence of symptomatic progression (increased pain in an area with known lesions confirmed on imaging).
  • All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 Grade 2 or less.
  • Men of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least 30 days after the last dose of study drug. The definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate.
  • Acceptable hematology and serum biochemistry screening values:
  • White Blood Cell Count (WBC) ≥ 3,000/mm3
  • Absolute Neutrophil Count (ANC) ≥ 1,500/mm3
  • Platelet (PLT) count ≥ 100,000/mm3
  • Hemoglobin (HGB) ≥ 9.0 g/dl
  • Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
  • Creatinine ≤ 1.5 x ULN
  • Albumin > 2.5 g/dL
  • Willing and able to comply with the protocol, including follow-up visits and examinations

Who cannot join

  • Treatment with cytotoxic chemotherapy within previous 4 weeks, or failure to recover from AEs down to grade 2 or less due to cytotoxic chemotherapy administered more than 4 weeks previous (however, ongoing neuropathy is permitted)
  • Receiving concurrent systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188) for the treatment of bony metastases. Prior therapy with radium-223 is not permitted.
  • Other malignancy treated within the last 3 years (except non melanoma skin cancer or low-grade superficial bladder cancer)
  • Visceral (i.e. liver, lung, etc) metastases (pulmonary nodules ≤1cm are permitted) as assessed by chest, abdominal or pelvic computed tomography (CT) (or other imaging modality)
  • Presence of active untreated CNS parenchymal or epidural spinal metastases
  • Lymphadenopathy exceeding 3 cm in short-axis diameter
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  • 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, such as but not limited to:
  • Any infection ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 Grade 2
  • Cardiac failure New York Heart Association (NYHA) III or IV
  • Crohn's disease or ulcerative colitis
  • Bone marrow dysplasia
  • Fecal incontinence
  • Inability to comply with the protocol and/or not willing or not available for follow-up assessments.
  • Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
  • Concurrent cytotoxic chemotherapy or anticancer therapies other than abiraterone, prednisone or other glucocorticoids, enzalutamide, androgen deprivation therapy, bisphosphonates, and denosumab.
  • Concurrent use of another investigational drug or device therapy (i.e., outside of study treatment) during, or within 2 weeks of treatment initiation.
  • Major surgery within 30 days prior to start of study drug.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Duke University Medical Center

    Durham, North Carolina, 27710

Other trials in United States

About this study

This study will examine biomarkers involved in osteomimicry in bone metastases and circulating tumor cells (CTCs) of men with mCRPC before and during therapy with the bone-targeting radiopharmaceutical radium-223. This study will also examine the bio-distribution of radium-223 in bone and bone metastases of men with mCRPC.

The investigators hypothesize that bone metastases and CTCs in men with mCRPC will commonly express markers of EMT/plasticity and osteomimicry, not just in the normal surrounding osteoblastic stroma but in the epithelial tumor cells themselves and that radium-223 will target both of these compartments including the more mesenchymal/osteoblastic tumor cells and the surrounding osteoblasts in the active bone microenvironment, with a relative sparing of normal bone and bone marrow.

Being tested
Biomarker analysis, Administration of radium-223

What participants receive

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

  • Biomarker analysisDevice

    Pharmacodynamic study of Radium-223 in bone biopsy and circulating tumor cell samples

  • Administration of radium-223Drug

    Subjects will receive radium-223 treatment for their disease as standard of care in this protocol. They will be receiving this treatment regardless of their participation in this protocol.

Study groups in NCT02204943
Study groupRoleWhat they receive
Bone Biopsy and Circulating Tumor Cell SamplesExperimentalNot described
Receives: Device: Biomarker analysis; Drug: Administration of radium-223

What is being measured

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

  1. Proportion of patients who overexpress alkaline phosphatase (ALP) in Circulating Tumor Cells (CTCs) at each time point

    The proportion of patients who over-express ALP in the CTCs, defined as any over-expression, will be estimated using descriptive statistics at each time point. ALP expression will be concurrently examined in the bone metastatic biopsies of men as well, if evaluable tissue is available.

    Measured: Cycle 1 Day 1, Cycle 3 Day 1 and Cycle 6 Day 1 or disease progression

Secondary outcomes (1)

  1. Change in biomarkers of epithelial plasticity and osteomimicry expressed in the bone metastases of men with bone metastatic CRPC

    Summary statistics of other biomarkers involved in epithelial plasticity and osteomimicry in the tumor tissue of men with bone metastatic CRPC including expression of ALP, PSA, CK, O-cadherin, N-cadherin, vimentin, TWIST, SNAIL, beta-catenin, ZEB1, androgen receptor (AR), AR variants (ARv) and γ-H2AX will be completed.

    Measured: At time of optional biopsy, pre- and post-treatment with Radium-223. Post-treatment biopsies will be approximately 10 and 22 weeks after first treatment.

Timeline

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

  1. First posted31 Jul 2014 (estimated)
  2. Study start6 May 2015
  3. Primary completion31 Jul 2017
  4. Study completion31 Jul 2017

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
Early Phase 1
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02204943
Sponsor's protocol ID
Pro00053925
Status last verified
Jun 2018
First submitted
28 Jul 2014
Last updated
8 Jun 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
Yes

Publications

  • Armstrong AJ, Gupta S, Healy P, Kemeny G, Leith B, Zalutsky MR, Spritzer C, Davies C, Rothwell C, Ware K, Somarelli JA, Wood K, Ribar T, Giannakakou P, Zhang J, Gerber D, Anand M, Foo WC, Halabi S, Gregory SG, George DJ. Pharmacodynamic study of radium-223 in men with bone metastatic castration resistant prostate cancer. PLoS One. 2019 May 28;14(5):e0216934. doi: 10.1371/journal.pone.0216934. eCollection 2019.

    PubMed 31136607

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Biomarker analysis and Administration of radium-223 in people with Bone Metastatic Castration-Resistant Prostate Cancer, run by Duke University 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 24 inclusion and 18 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 8 Jun 2018. 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Proportion of patients who overexpress alkaline phosphatase (ALP) in Circulating Tumor Cells (CTCs) at each time point (time frame: Cycle 1 Day 1, Cycle 3 Day 1 and Cycle 6 Day 1 or disease progression). 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 NCT02204943, 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 8 Jun 2018.

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