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

NCT03458559 | Unknown Phase 3 DMC

• 1 other identifier: 2017.610
• Study Type: interventional
• Target: 402
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer Metastatic to Bone

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Time from randomization until death due to any cause,

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

Secondary Outcomes (7)

• 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 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)

• Clinical progression

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

• Time to first SRE

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

• Quality of life

  Assessed through study completion, an average of 1 year

Study Arms (2)

Radium-223-chloride

ACTIVE COMPARATOR

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

Drug: Radium-223 chloride

Rhenium-188-HEDP

EXPERIMENTAL

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

Drug: Rhenium-188-HEDP

Interventions

Radium-223 chloride DRUG

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

Also known as: Xofigo, Radium-223 dichloride

Radium-223-chloride

Rhenium-188-HEDP DRUG

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

Also known as: Re-188-HEDP, 188Rhenium-etidronate

Rhenium-188-HEDP

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (1)

VU University Medical Center

Amsterdam, 1081 HV, Netherlands

Location

Related Publications (3)

• 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.

  PMID: 12885803 BACKGROUND

• 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.

  PMID: 21976530 BACKGROUND

• 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.

  PMID: 26391636 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

radium Ra 223 dichloride; rhenium-186 HEDP

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Alfons JM van den Eertwegh, Prof.dr.

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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)

Study Record Dates

• First Submitted: February 14, 2018
• First Posted: March 8, 2018
• Study Start: May 16, 2018
• Primary Completion: May 16, 2022
• Study Completion: May 16, 2024
• Last Updated: November 17, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)