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

Sponsor

Amsterdam UMC, location VUmc (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03458559

Collaborator

(none)

402

Enrollment

Location

Arms

Anticipated Duration (Months)

5.6

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

Anticipated 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)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

Anticipated Primary Completion Date :

May 16, 2022

Anticipated Study Completion Date :

May 16, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Overall survival [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

Time to PSA progression [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 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 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 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 [Assessed through study completion, an average of 1 year]
Measured by the EORTC quality of Life Questionnaire C30
Effect on pain [Assessed through study completion, an average of 1 year]
Measured with a visual analogue scale
Incremental Cost Effectiveness Ratio (IVER) [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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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.