Overview

This trial is active, not recruiting.

Condition prostatic neoplasms
Treatments radium-223 dichloride (xofigo, bay88-8223), matching placebo (normal saline), abiraterone, prednisone/prednisolone
Phase phase 3
Sponsor Bayer
Collaborator Janssen Research & Development, LLC
Start date March 2014
End date December 2017
Trial size 806 participants
Trial identifier NCT02043678, 15396, 2013-003438-33

Summary

To determine if the addition of radium-223 dichloride to standard treatment is able to prolong life and to delay events specific for prostate cancer which has spread to the bone, such as painful fractures or bone pain which needs to be treated with an X-ray machine.

United States Maryland, Massachusetts, and Missouri
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Radium-223 dichloride +abiraterone+prednisone/prednisolone All study subjects will receive treatment with oral abiraterone acetate (1000 mg once daily), oral prednisone/prednisolone (5 mg twice daily), with best supportive care
radium-223 dichloride (xofigo, bay88-8223)
50 kBq/kg body weight, intravenous injection (IV-slow bolus), every 4 weeks for 6 cycles.(nominal change to 55 kBq/kg after implementation of National Institute of Standards and Technology (NIST) update)
abiraterone
All study subjects will receive treatment with oral abiraterone acetate (1000 mg once daily),with best supportive care
prednisone/prednisolone
All study subjects will receive treatment with oral prednisone/prednisolone (5 mg twice daily), with best supportive care
(Placebo Comparator)
Placebo+abiraterone+prednisone/prednisolone All study subjects will receive treatment with oral abiraterone acetate (1000 mg once daily), oral prednisone/prednisolone (5 mg twice daily), with best supportive care
matching placebo (normal saline)
Intravenous injection ( IV-slow bolus), every 4 weeks for 6 cycles
abiraterone
All study subjects will receive treatment with oral abiraterone acetate (1000 mg once daily),with best supportive care
prednisone/prednisolone
All study subjects will receive treatment with oral prednisone/prednisolone (5 mg twice daily), with best supportive care

Primary Outcomes

Measure
Symptomatic skeletal event free survival (SSE-FS).
time frame: At 3 years

Secondary Outcomes

Measure
Overall Survival
time frame: At 3 years for interim and at 6 years for final.
Time to opiate use for cancer pain
time frame: At 3 years
Time to pain progression
time frame: At 3 years
Time to cytotoxic chemotherapy
time frame: At 3 years
Radiological progression free survival (rPFS)
time frame: At 3 years
Number of participants with adverse events as a measure of safety and tolerability.
time frame: Up to 3 years

Eligibility Criteria

Male participants at least 18 years old.

Inclusion Criteria: - Histologically confirmed adenocarcinoma of the prostate - Male subjects of age ≥ 18 years - Prostate cancer progression documented by prostate specific antigen according to the Prostate Cancer Working Group 2 (PCWG2) criteria or radiological progression according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. - Two or more bone metastases on bone scan within 4 weeks prior to randomization with no lung, liver, other visceral and/or brain metastasis. - Asymptomatic or mildly symptomatic prostate cancer. - Subjects who received combined androgen blockade with an anti-androgen must have shown PSA(prostate specific antigen) progression after discontinuing the anti-androgen prior to enrollment. - Medical or surgical castration with testosterone less than 50 ng/dL (1.7nmol/L). - Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 Exclusion Criteria: - Prior cytotoxic chemotherapy for the treatment of CRPC, including taxanes, mitoxantrone and estramustine - Any chronic medical condition requiring a higher dose of corticosteroid than 5 mg prednisone/prednisolone bid. - Pathological finding consistent with small cell carcinoma of the prostate - History of visceral metastasis, or presence of visceral metastasis detected by screening imaging examinations - History of or known brain metastasis. - Malignant lymphadenopathy exceeding 3 cm in short-axis diameter. - Blood transfusion or erythropoietin stimulating agents prior 4 weeks of screening and during the whole screening period before randomization - Imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Subjects with history of spinal cord compression should have completely recovered - Use of opiate analgesics for cancer-related pain, including codeine and dextropropoxyphene, currently or anytime during the 4- week period prior to randomization.

Additional Information

Official title A Phase III Randomized, Double-blind, Placebo-controlled Trial of Radium-223 Dichloride in Combination With Abiraterone Acetate and Prednisone/Prednisolone in the Treatment of Asymptomatic or Mildly Symptomatic Chemotherapy-naïve Subjects With Bone Predominant Metastatic Castration-resistant Prostate Cancer(CRPC)
Description This study is a phase III multinational, multicenter,randomized, double blind, placebo controlled, study with a randomization allocation ratio of 1:1 (radium-223 dichloride plus abiraterone acetate plus prednisone/prednisolone: placebo plus abiraterone acetate plus prednisone/prednisolone).The study period will consist of screening/randomization, treatment, active follow-up with clinic visits, active follow-up without clinic visits, and long-term follow-up phases. In this study, subjects will receive study treatment (radium-223 dichloride or placebo in addition to abiraterone acetate plus prednisone/prednisolone for the first 6 cycles followed by abiraterone acetate plus prednisone/prednisolone thereafter) until an on-study symptomatic skeletal event (SSE) occurs (or other withdrawal criteria are met). Follow-up will continue for up to 7 years or until the subject dies, is lost to followup, or withdraws informed consent and actively objects to collection of further data.This study will be conducted at approximately 150 investigative study centers and approximately 800 subjects will be enrolled.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Bayer.