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

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ClinicalTrials.gov Identifier: NCT03458559
Recruitment Status : Active, not recruiting
First Posted : March 8, 2018
Last Update Posted : August 29, 2019
Sponsor:
Information provided by (Responsible Party):
A.J.M. van den Eertwegh, VU University Medical Center

Brief 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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Metastatic to Bone Drug: Radium-223 chloride Drug: Rhenium-188-HEDP Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 402 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
Official Title: Repeated Rhenium-188-HEDP Versus Radium-223-chloride in Patients With Metastatic Castration-resistant Prostate Cancer: The RaRe Study
Actual Study Start Date : May 16, 2018
Estimated Primary Completion Date : May 16, 2022
Estimated Study Completion Date : May 16, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

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




Primary Outcome Measures :
  1. 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,


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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

  5. Quality of life [ Time Frame: Assessed through study completion, an average of 1 year ]
    Measured by the EORTC quality of Life Questionnaire C30

  6. Effect on pain [ Time Frame: Assessed through study completion, an average of 1 year ]
    Measured with a visual analogue scale

  7. 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)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03458559


Locations
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Netherlands
VU University Medical Center
Amsterdam, Netherlands, 1081 HV
Sponsors and Collaborators
VU University Medical Center
Investigators
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Principal Investigator: Alfons JM van den Eertwegh, Prof.dr. VU University Medical Center

Publications:
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Responsible Party: A.J.M. van den Eertwegh, Principal Investigator, VU University Medical Center
ClinicalTrials.gov Identifier: NCT03458559     History of Changes
Other Study ID Numbers: 2017.610
First Posted: March 8, 2018    Key Record Dates
Last Update Posted: August 29, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by A.J.M. van den Eertwegh, VU University Medical Center:
Bone metastases
Rhenium-188-HEDP
Radium 223-chloride
Survival
Prostate cancer
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Etidronic Acid
Radium Ra 223 dichloride
Antineoplastic Agents
Bone Density Conservation Agents
Physiological Effects of Drugs