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Prostate Cancer Metastatic to BonePhase 3RaReNCT03458559

Rhenium-188-HEDP vs. Radium-223-chloride in Patients With Advanced Prostate Cancer Refractory to Hormonal Therapy

A Phase 3 study testing Radium-223 chloride and Rhenium-188-HEDP in people with Prostate Cancer Metastatic to Bone, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Radium-223 chloride is an alpha-emitting radiopharmaceutical with proven survival benefit in patients with castration-resistant prostate cancer metastatic to bone. Beta-emitting radiopharmaceuticals have proven efficacy for palliating malignant bone pain. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer Metastatic to Bone
What is being tested?
Radium-223 chloride and Rhenium-188-HEDP
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
402 participants
Where
1 siteNetherlands
Study dates
16 May 2018to 16 May 2024
Phase
Phase 3
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

  • Male, 18 years or older
  • Histologically confirmed prostate cancer
  • Bone metastases (≥ 6 lesions) showing pathological uptake at bone scintigraphy.
  • WHO performance status of ≤2
  • Life expectancy of at least 6 months
  • Castration-resistant disease: serum testosterone level of ≤ 1.7 nmol per liter (≤50 ng per deciliter) after bilateral orchiectomy or during maintenance treatment consisting of androgen-ablation therapy with a luteinizing hormone-releasing hormone agonist. During study treatment the maintenance androgen-deprivation therapy must be continued.
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  • Baseline PSA ≥5 ng/ml with evidence of progressively increasing PSA values
  • Symptomatic disease with either regular use of analgesic medication or treatment with external-beam radiotherapy for cancer-related bone pain within the previous 12 weeks.
  • Progression on or after treatment with docetaxel, or inability to receive docetaxel.
  • Adequate renal function (serum creatinine level ≤1.5 x ULN)
  • Adequate hematological function defined as absolute neutrophil count ≥ 1.5x10^9/L and platelet count ≥100x 10^9/L)
  • Written informed consent

Who cannot join

  • Treatment with chemotherapy within the previous 4 weeks
  • Continuation of treatment with abiraterone or enzalutamide
  • Previous hemibody external radiotherapy
  • Systemic radiotherapy with radioisotopes within the previous 24 weeks
  • Malignant lymphadenopathy ≥3cm in the short-axis diameter
  • Presence of visceral metastases
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  • Imminent of established spinal cord compression
  • Active uncontrolled bacterial, viral or fungal infection
  • History of another malignancy within the last five years except adequately treated basal cell carcinoma of the skin
  • Organ allografts requiring immunosuppressive therapy.
  • Any serious uncontrolled concommitant disease
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule: those conditions should be discussed with the patient before registration in the trial.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • VU University Medical Center

    Amsterdam, 1081 HV

Other trials in Netherlands

About this study

Official title: Repeated Rhenium-188-HEDP Versus Radium-223-chloride in Patients With Metastatic Castration-resistant Prostate Cancer: The RaRe Study

Radium-223 chloride is an alpha-emitting radiopharmaceutical with proven survival benefit in patients with castration-resistant prostate cancer metastatic to bone. Beta-emitting radiopharmaceuticals have proven efficacy for palliating malignant bone pain. Nowadays, rhenium-188-HEDP is used in clinical practice for pain relief and palliative care. Several studies suggest that also rhenium-188-HEDP has the potential to improve overall survival. The purpose of this study is to investigate if treatment with rhenium-188-HEDP results in improvement of overall survival compared to treatment with radium-223-chloride.

Read the detailed description

The main objective of this trial is to compare rhenium-188-HEDP (a beta-emitting radiopharmaceutical) with radium-223-chloride (an alfa-emitting radiopharmaceutical), in patients with castration-resistant prostate cancer metastatic to bone, with overall survival as primary endpoint.

For radium-223-chloride, an overall survival benefit has been proven in a large randomized phase III trial. Although such a trial has never been performed for rhenium-188-HEDP, some trials in literature suggest a survival benefit for rhenium as well.

Rhenium has some advantages compared to radium. Firstly, it is easily available as it can be produced in the hospital. Secondly, the costs of rhenium are significantly lower compared to radium. Lastly, rhenium seems to have a favorable pain response. However, no randomized trials have been performed to confirm this.

Being tested
Radium-223 chloride, Rhenium-188-HEDP
Keywords
Bone metastases, Rhenium-188-HEDP, Radium 223-chloride, Survival, Prostate cancer
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-223 chlorideDrug

    Also called Xofigo, Radium-223 dichloride

    Intravenously 50 kBq/kg every 4 weeks. Total: 6 administrations

  • Rhenium-188-HEDPDrug

    Also called Re-188-HEDP, 188Rhenium-etidronate

    Intravenously 40 MBq/kg every 8 weeks. Total: 3 administrations

Study groups in NCT03458559
Study groupRoleWhat they receive
Radium-223-chlorideActive comparatorRadium-223-chloride 50kBg/kg, every 4 weeks intravenously, for a total of 6 administrations.
Receives: Drug: Radium-223 chloride
Rhenium-188-HEDPExperimentalRhenium-188-HEDP 40MBq/kg, every 8 weeks intravenously, for a total of 3 administrations.
Receives: Drug: Rhenium-188-HEDP

What is being measured

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

  1. Overall survival

    Time from randomization until death due to any cause,

    Measured: Time from randomization until death due to any cause, an average of 18 months

Secondary outcomes (7)

  1. Time to PSA progression

    Time from randomization to the date of a minimum of rising PSA levels with an interval of >1week between each determination

    Measured: Time from randomization to the date of a minimum of rising PSA levels, an average of 8 months (PSA measured at baseline and every 4 weeks).

  2. Time to total-ALP progression

    Time from randomization to the date of earliest objective evidence of ALP progression.

    Measured: Time from randomization to the date of earliest objective evidence of ALP progression, an average of 8 months (ALP measure at baseline and every 4 weeks)

  3. Clinical progression

    Time from randomization to the date of first clinical progression.

    Measured: Time from randomization to the date of first clinical progression, an average of 12 months

  4. Time to first SRE

    Time from randomization to the date of first skeletal related events

    Measured: Time from randomization to the date of first skeletal related events, an average of 12 months

  5. Quality of life

    Measured by the EORTC quality of Life Questionnaire C30

    Measured: Assessed through study completion, an average of 1 year

  6. Effect on pain

    Measured with a visual analogue scale

    Measured: Assessed through study completion, an average of 1 year

  7. Incremental Cost Effectiveness Ratio (IVER)

    Ratio between the difference in costs and the difference in benefits (quality of life of treatment with rhenium-188-HEDP of radium-223-chloride)

    Measured: Assessed through study completion, an average of 1 year

Timeline

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

  1. First posted8 Mar 2018
  2. Study start16 May 2018
  3. Primary completion16 May 2022 (estimated)
  4. Study completion16 May 2024 (estimated)

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Patients will be randomized between * radium-223-chloride intravenously, for a total of 6 administrations (every 4weeks) * rhenium-188-HEDP intravenously for a total of 3 administratrions (every 8 weeks)
Masking
None (open label)
Enrolment
402 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03458559
Sponsor's protocol ID
2017.610
Acronym
RaRe
Status last verified
Nov 2020
First submitted
14 Feb 2018
Last updated
17 Nov 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Palmedo H, Manka-Waluch A, Albers P, Schmidt-Wolf IG, Reinhardt M, Ezziddin S, Joe A, Roedel R, Fimmers R, Knapp FF Jr, Guhlke S, Biersack HJ. Repeated bone-targeted therapy for hormone-refractory prostate carcinoma: tandomized phase II trial with the new, high-energy radiopharmaceutical rhenium-188 hydroxyethylidenediphosphonate. J Clin Oncol. 2003 Aug 1;21(15):2869-75. doi: 10.1200/JCO.2003.12.060.

    PubMed 12885803

  • Biersack HJ, Palmedo H, Andris A, Rogenhofer S, Knapp FF, Guhlke S, Ezziddin S, Bucerius J, von Mallek D. Palliation and survival after repeated (188)Re-HEDP therapy of hormone-refractory bone metastases of prostate cancer: a retrospective analysis. J Nucl Med. 2011 Nov;52(11):1721-6. doi: 10.2967/jnumed.111.093674. Epub 2011 Oct 5.

    PubMed 21976530

  • Jong JM, Oprea-Lager DE, Hooft L, de Klerk JM, Bloemendal HJ, Verheul HM, Hoekstra OS, van den Eertwegh AJ. Radiopharmaceuticals for Palliation of Bone Pain in Patients with Castration-resistant Prostate Cancer Metastatic to Bone: A Systematic Review. Eur Urol. 2016 Sep;70(3):416-26. doi: 10.1016/j.eururo.2015.09.005. Epub 2015 Sep 19.

    PubMed 26391636

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Radium-223 chloride and Rhenium-188-HEDP in people with Prostate Cancer Metastatic to Bone, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.

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 12 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 17 Nov 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 Netherlands. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

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?

Overall survival (time frame: Time from randomization until death due to any cause, an average of 18 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 NCT03458559, which also lists 3 linked publications.

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 17 Nov 2020.

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