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Status unknownNCT03458559RaReUpdated Nov 17, 2020

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

A Phase 3 interventional study of Radium-223 chloride and Rhenium-188-HEDP in Prostate Cancer Metastatic to Bone, sponsored by Amsterdam UMC, location VUmc. Status unknown at 1 site in Netherlands. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-11-17.

Sponsored by Amsterdam UMC, location VUmc · Phase 3, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Nov 2020), so the status shown — last known as Active, not recruiting — may be out of date.
Phase
Phase 3
Study type
Interventional
Enrollment
402
Allocation
Randomized
Ages
18 Years and older
Sex
Male
01

Study 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. 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.

02

Conditions studied

  • Prostate Cancer Metastatic to Bone

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Keywords

  • Bone metastases
  • Rhenium-188-HEDP
  • Radium 223-chloride
  • Survival
  • Prostate cancer
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Male
Accepts healthy volunteers
No

Inclusion criteria

  • 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.
  • 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

Exclusion criteria

Exclusion Criteria:

  • 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
  • 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.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
402 participants (estimated)

Study arms

  • Active comparator
    Radium-223-chloride

    Radium-223-chloride 50kBg/kg, every 4 weeks intravenously, for a total of 6 administrations.

    Drug: Radium-223 chloride

  • Experimental
    Rhenium-188-HEDP

    Rhenium-188-HEDP 40MBq/kg, every 8 weeks intravenously, for a total of 3 administrations.

    Drug: Rhenium-188-HEDP

Interventions

  • DrugRadium-223 chloride

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

    Also known as: Xofigo, Radium-223 dichloride

  • DrugRhenium-188-HEDP

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

    Also known as: Re-188-HEDP, 188Rhenium-etidronate

05

What researchers measure

Primary outcomes

  1. Overall survival

    Time from randomization until death due to any cause,

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

Secondary outcomes

  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

    Time frame: 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.

    Time frame: 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.

    Time frame: 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

    Time frame: 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

    Time frame: Assessed through study completion, an average of 1 year

  6. Effect on pain

    Measured with a visual analogue scale

    Time frame: 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)

    Time frame: Assessed through study completion, an average of 1 year

06

Study locations

1 site
  • VU University Medical Center
    Amsterdam, 1081 HV, Netherlands
07

References and documents

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 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03458559
Lead sponsor
Amsterdam UMC, location VUmc
Responsible party
A.J.M. van den Eertwegh (Principal Investigator, Amsterdam UMC, location VUmc) — Principal investigator
First posted
Mar 8, 2018
Start date
May 16, 2018
Primary completion
May 16, 2022 (estimated)
Completion
May 16, 2024 (estimated)
Last update
Nov 17, 2020

Study contacts

Alfons JM van den Eertwegh, Prof.dr.
principal investigator · Amsterdam UMC, location VUmc

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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