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

Primary Purpose

Prostate Cancer Metastatic to Bone

Status

Active

Phase

Phase 3

Locations

Netherlands

Study Type

Interventional

Intervention

Radium-223 chloride

Rhenium-188-HEDP

About this trial

This is an interventional treatment trial for Prostate Cancer Metastatic to Bone focused on measuring Bone metastases, Rhenium-188-HEDP, Radium 223-chloride, Survival, Prostate cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept 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.

Sites / Locations

VU University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Radium-223-chloride

Rhenium-188-HEDP

Arm Description

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

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

Outcomes

Primary Outcome Measures

Overall survival

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 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.

Clinical progression

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

Quality of life

Measured by the EORTC quality of Life Questionnaire C30

Effect on pain

Measured with a visual analogue scale

Incremental Cost Effectiveness Ratio (IVER)

Ratio between the difference in costs and the difference in benefits (quality of life of treatment with rhenium-188-HEDP of radium-223-chloride)

Full Information

NCT ID

NCT03458559

First Posted

February 14, 2018

Last Updated

November 16, 2020

Sponsor

Amsterdam UMC, location VUmc

1. Study Identification

Unique Protocol Identification Number

NCT03458559

Brief Title

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

Acronym

RaRe

Official Title

Repeated Rhenium-188-HEDP Versus Radium-223-chloride in Patients With Metastatic Castration-resistant Prostate Cancer: The RaRe Study

Study Type

Interventional

2. Study Status

Record Verification Date

November 2020

Overall Recruitment Status

Active, not recruiting

Study Start Date

May 16, 2018 (Actual)

Primary Completion Date

May 16, 2022 (Anticipated)

Study Completion Date

May 16, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Amsterdam UMC, location VUmc

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer Metastatic to Bone

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

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)

Allocation

Randomized

Enrollment

402 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Radium-223-chloride

Arm Type

Active Comparator

Arm Description

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

Arm Title

Rhenium-188-HEDP

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Radium-223 chloride

Other Intervention Name(s)

Xofigo, Radium-223 dichloride

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Rhenium-188-HEDP

Other Intervention Name(s)

Re-188-HEDP, 188Rhenium-etidronate

Intervention Description

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

Primary Outcome Measure Information:

Title

Overall survival

Description

Time from randomization until death due to any cause,

Time Frame

Time from randomization until death due to any cause, an average of 18 months

Secondary Outcome Measure Information:

Title

Time to PSA progression

Description

Time from randomization to the date of a minimum of rising PSA levels with an interval of >1week between each determination

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).

Title

Time to total-ALP progression

Description

Time from randomization to the date of earliest objective evidence of 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)

Title

Clinical progression

Description

Time from randomization to the date of first clinical progression.

Time Frame

Time from randomization to the date of first clinical progression, an average of 12 months

Title

Time to first SRE

Description

Time from randomization to the date of first skeletal related events

Time Frame

Time from randomization to the date of first skeletal related events, an average of 12 months

Title

Quality of life

Description

Measured by the EORTC quality of Life Questionnaire C30

Time Frame

Assessed through study completion, an average of 1 year

Title

Effect on pain

Description

Measured with a visual analogue scale

Time Frame

Assessed through study completion, an average of 1 year

Title

Incremental Cost Effectiveness Ratio (IVER)

Description

Ratio between the difference in costs and the difference in benefits (quality of life of treatment with rhenium-188-HEDP of radium-223-chloride)

Time Frame

Assessed through study completion, an average of 1 year

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alfons JM van den Eertwegh, Prof.dr.

Organizational Affiliation

Amsterdam UMC, location VUmc

Official's Role

Principal Investigator

Facility Information:

Facility Name

VU University Medical Center

City

Amsterdam

ZIP/Postal Code

1081 HV

Country

Netherlands

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

12885803

Citation

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.

Results Reference

background

PubMed Identifier

21976530

Citation

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.

Results Reference

background

PubMed Identifier

26391636

Citation

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.

Results Reference

background

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

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