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Phase 3 N=806 Randomized Quadruple-blind Treatment

Radium-223 Dichloride and Abiraterone Acetate Compared to Placebo and Abiraterone Acetate for Men With Cancer of the Prostate When Medical or Surgical Castration Does Not Work and When the Cancer Has Spread to the Bone, Has Not Been Treated With Chemotherapy and is Causing no or Only Mild Symptoms

Prostatic Neoplasms

Enrolled (actual)
806
Serious AEs
48.9%
Results posted
Mar 2019
Primary outcome: Primary: Symptomatic Skeletal Event Free Survival (SSE-FS) — 22.3; 26.0 Months — p=0.2636

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Radium-223 dichloride (Xofigo, BAY88-8223) (Drug); Matching placebo (normal saline) (Drug); Abiraterone (Drug); Prednisone/Prednisolone (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
Male
Sponsor
Bayer
Primary completion
Feb 2018

Outcome Measures

OutcomeResultp-value
PRIMARY
Symptomatic Skeletal Event Free Survival (SSE-FS)
22.3; 26.0 0.2636
SECONDARY
Overall Survival (OS)
30.1; 34.8 0.1194
SECONDARY
Radiological Progression Free Survival (rPFS)
11.2; 12.4 0.1283
SECONDARY
Time to Pain Progression
14.4; 18.7 0.1669
SECONDARY
Time to Cytotoxic Chemotherapy
29.5; 28.5 0.7871
SECONDARY
Time to Opiate Use for Cancer Pain
19.0; 22.6 0.2467
SECONDARY
Number of Participants With Treatment-emergent Adverse Events
382; 387; 265; 273; 92; 91
SECONDARY
Number of Participants With Radium-223/Placebo-related Treatment-emergent Adverse Events Per Maximum Intensity
43; 53; 28; 23; 20; 13
SECONDARY
Number of Participants With Any Treatment-emergent Additional Primary Malignancies
32; 30
SECONDARY
Number of Participants With Treatment-emergent Bone Fractures
110; 51
SECONDARY
Number of Participants With Post-treatment Adverse Events
148; 138; 20; 10; 31; 34
SECONDARY
Number of Participants With Any Study Drug-related Post-treatment Adverse Events Per Maximum Intensity
34; 4; 9; 3; 6; 3
SECONDARY
Number of Participants With Post-treatment Additional Primary Malignancies
7; 7
SECONDARY
Number of Participants With Post-treatment Chemotherapy-related Blood and Lymphatic System Disorders
5; 4; 1; 0; 5; 8
SECONDARY
Number of Participants With Post-treatment Bone Fractures
0; 1; 1; 0; 1; 0

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.

Eligibility Criteria

Inclusion Criteria

  • Histologically confirmed adenocarcinoma of the prostate
  • Male subjects of age ≥ 18 years
  • Prostate cancer progression documented by prostate specific antigen (PSA) 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 progression after discontinuing the anti-androgen prior to enrollment
  • Maintenance of medical castration or surgical castration with testosterone less than 50 ng/dL (1.7nmol/L)
  • Eastern Cooperative Oncology Group performance status (ECOG PS) score 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 twice daily
  • 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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02043678). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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