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

NCT ID: NCT03458559

Last Updated: 2020-11-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

402 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-16

Study Completion Date

2024-05-16

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Prostate Cancer Metastatic to Bone

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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)
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Radium-223-chloride

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

Group Type ACTIVE_COMPARATOR

Radium-223 chloride

Intervention Type DRUG

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

Rhenium-188-HEDP

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

Group Type EXPERIMENTAL

Rhenium-188-HEDP

Intervention Type DRUG

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

Interventions

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Radium-223 chloride

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

Intervention Type DRUG

Rhenium-188-HEDP

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

Intervention Type DRUG

Other Intervention Names

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Xofigo Radium-223 dichloride Re-188-HEDP 188Rhenium-etidronate

Eligibility Criteria

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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

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Amsterdam UMC, location VUmc

OTHER

Sponsor Role lead

Responsible Party

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A.J.M. van den Eertwegh

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Alfons JM van den Eertwegh, Prof.dr.

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC, location VUmc

Locations

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VU University Medical Center

Amsterdam, , Netherlands

Site Status

Countries

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Netherlands

References

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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.

Reference Type BACKGROUND
PMID: 12885803 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21976530 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26391636 (View on PubMed)

Other Identifiers

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2017.610

Identifier Type: -

Identifier Source: org_study_id