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

November 16, 2020 updated by: A.J.M. van den Eertwegh, Amsterdam UMC, location VUmc

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

402

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Amsterdam, Netherlands, 1081 HV
        • VU University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Radium-223-chloride
Radium-223-chloride 50kBg/kg, every 4 weeks intravenously, for a total of 6 administrations.
Drug: Radium-223 chloride
Intravenously 50 kBq/kg every 4 weeks. Total: 6 administrations
Other Names:
  • Xofigo
  • Radium-223 dichloride
Experimental: Rhenium-188-HEDP
Rhenium-188-HEDP 40MBq/kg, every 8 weeks intravenously, for a total of 3 administrations.
Drug: Rhenium-188-HEDP
Intravenously 40 MBq/kg every 8 weeks. Total: 3 administrations
Other Names:
  • Re-188-HEDP
  • 188Rhenium-etidronate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Time from randomization until death due to any cause, an average of 18 months
Time from randomization until death due to any cause,
Time from randomization until death due to any cause, an average of 18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to PSA progression
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).
Time from randomization to the date of a minimum of rising PSA levels with an interval of >1week between each determination
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).
Time to total-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)
Time from randomization to the date of earliest objective evidence of ALP progression.
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)
Clinical progression
Time Frame: Time from randomization to the date of first clinical progression, an average of 12 months
Time from randomization to the date of first clinical progression.
Time from randomization to the date of first clinical progression, an average of 12 months
Time to first SRE
Time Frame: Time from randomization to the date of first skeletal related events, an average of 12 months
Time from randomization to the date of first skeletal related events
Time from randomization to the date of first skeletal related events, an average of 12 months
Quality of life
Time Frame: Assessed through study completion, an average of 1 year
Measured by the EORTC quality of Life Questionnaire C30
Assessed through study completion, an average of 1 year
Effect on pain
Time Frame: Assessed through study completion, an average of 1 year
Measured with a visual analogue scale
Assessed through study completion, an average of 1 year
Incremental Cost Effectiveness Ratio (IVER)
Time Frame: Assessed through study completion, an average of 1 year
Ratio between the difference in costs and the difference in benefits (quality of life of treatment with rhenium-188-HEDP of radium-223-chloride)
Assessed through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amsterdam UMC, location VUmc

Investigators

  • Principal Investigator: Alfons JM van den Eertwegh, Prof.dr., Amsterdam UMC, location VUmc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 16, 2018

Primary Completion (Anticipated)

May 16, 2022

Study Completion (Anticipated)

May 16, 2024

Study Registration Dates

First Submitted

February 14, 2018

First Submitted That Met QC Criteria

March 7, 2018

First Posted (Actual)

March 8, 2018

Study Record Updates

Last Update Posted (Actual)

November 17, 2020

Last Update Submitted That Met QC Criteria

November 16, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017.610

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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