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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE February 14, 2018
First Posted Date  ICMJE March 8, 2018
Last Update Posted Date August 29, 2019
Actual Study Start Date  ICMJE May 16, 2018
Estimated Primary Completion Date May 16, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 7, 2018)
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,
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03458559 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 7, 2018)
  • 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 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.
  • 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 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
  • Quality of life [ Time Frame: Assessed through study completion, an average of 1 year ]
    Measured by the EORTC quality of Life Questionnaire C30
  • Effect on pain [ Time Frame: Assessed through study completion, an average of 1 year ]
    Measured with a visual analogue scale
  • 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)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Rhenium-188-HEDP vs. Radium-223-chloride in Patients With Advanced Prostate Cancer Refractory to Hormonal Therapy
Official Title  ICMJE Repeated Rhenium-188-HEDP Versus Radium-223-chloride in Patients With Metastatic Castration-resistant Prostate Cancer: The RaRe Study
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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
Condition  ICMJE Prostate Cancer Metastatic to Bone
Intervention  ICMJE
  • Drug: Radium-223 chloride
    Intravenously 50 kBq/kg every 4 weeks. Total: 6 administrations
    Other Names:
    • Xofigo
    • Radium-223 dichloride
  • Drug: Rhenium-188-HEDP
    Intravenously 40 MBq/kg every 8 weeks. Total: 3 administrations
    Other Names:
    • Re-188-HEDP
    • 188Rhenium-etidronate
Study Arms  ICMJE
  • Active Comparator: Radium-223-chloride
    Radium-223-chloride 50kBg/kg, every 4 weeks intravenously, for a total of 6 administrations.
    Intervention: Drug: Radium-223 chloride
  • Experimental: Rhenium-188-HEDP
    Rhenium-188-HEDP 40MBq/kg, every 8 weeks intravenously, for a total of 3 administrations.
    Intervention: Drug: Rhenium-188-HEDP
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: March 7, 2018)
402
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 16, 2024
Estimated Primary Completion Date May 16, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03458559
Other Study ID Numbers  ICMJE 2017.610
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party A.J.M. van den Eertwegh, VU University Medical Center
Study Sponsor  ICMJE VU University Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Alfons JM van den Eertwegh, Prof.dr. VU University Medical Center
PRS Account VU University Medical Center
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP