A Placebo-controlled Phase II Study of Bone-targeted Radium-223 in Symptomatic Hormone-refractory Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00459654
Recruitment Status : Completed
First Posted : April 12, 2007
Last Update Posted : June 25, 2014
Information provided by (Responsible Party):

Brief Summary:
The purpose of this study is to evaluate the effectiveness of the investigational radioisotope Radium-223 in treatment of men with prostate cancer and bone metastases that no longer respond to hormonal treatment.

Condition or disease Intervention/treatment Phase
Prostate Cancer Neoplasm Metastasis Drug: Radium-223 dichloride (BAY88-8223) Drug: Saline Phase 2

Detailed Description:

Primary objective:

To study the biological effectiveness of radium-223 therapy measured as:

  • Time to occurrence of skeletal-related events(SREs)
  • Change in bone-specific alkaline phosphatase (bone-ALP) levels

Secondary objectives:

To study the efficacy of radium-223 therapy in terms of:

  • Frequency of new SREs
  • Proportions of patients with an SRE
  • Proportions of patients with SRE at different time points
  • Changes of biochemical markers of bone turnover
  • Treatment response with regard to pain and analgesic use(termed "Palliative effect" in study protocol)
  • Quality of life assessment
  • Overall survival To study the safety of the repeated radium-223 regimen Total Enrollment:64 Study start: February 2004

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II Randomised, Placebo-controlled, Multicentre Study in Prostate Cancer Patients With Painful Bone Metastases to Evaluate the Efficacy of Repeated Radium-223 Injections
Study Start Date : February 2004
Actual Primary Completion Date : May 2006
Actual Study Completion Date : May 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Radium-223 dichloride (Xofigo, BAY88-8223)
Each subject receives local filed external beam radiotherapy (EBR) and repeated injections of the investigational drug radium-223 (EBR+Radium-223)
Drug: Radium-223 dichloride (BAY88-8223)
Four Radium-223 injections were given at 4-weekly intervals starting after the first fraction of EBR.
Placebo Comparator: Saline
Each subject receives local filed external beam radiotherapy (EBR) and repeated injections of saline (EBR+placebo)
Drug: Saline
Four Saline injections were given at 4-weekly intervals starting after the first fraction of EBR.

Primary Outcome Measures :
  1. Time to occurrence of Skeletal-related Events (SRE) [ Time Frame: Up to 12 Month ]
    SREs are defined as: Increase in pain severity index during the last week; Increase in analgesic consumption; Neurological symptoms secondary to skeletal manifestations of prostate cancer; New pathologic bone fractures (vertebral and non-vertebral); Tumour related orthopaedic surgical intervention; Subsequent external beam radiation to relieve skeletal pain; Use of radioisotopes to relieve new skeletal related symptoms; Use of corticosteroids for skeletal pain, at doses aimed for pain palliation; Use of chemotherapy, bisphosphonates, or hormones, for the treatment of skeletal disease progression

  2. Relative change (%) in bone-ALP levels from baseline to 4 weeks after last injection [ Time Frame: Up to 12 Month ]

Secondary Outcome Measures :
  1. Number of SREs per patient [ Time Frame: Up to 12 Month ]
  2. Changes in the levels of biochemical markers of bone formation [ Time Frame: Up to 12 Month ]
  3. Change in Prostate Specific Antigen (PSA) [ Time Frame: Up to 12 Month ]
  4. Change in pain level [ Time Frame: Up to 12 Month ]
  5. Changes in analgesic use during study period [ Time Frame: Up to 12 Month ]
  6. Changes in Edmonton Symptom Assessment Scale (ESAS) from baseline [ Time Frame: Up to 12 Month ]
  7. Overall survival [ Time Frame: up to 24 months ]
  8. Adverse events [ Time Frame: up to 24 months ]
  9. Clinical laboratory tests including haematology, renal and liver function parameters [ Time Frame: up to 24 months ]

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Ages Eligible for Study:   40 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically/cytologically confirmed adenocarcinoma of the prostate
  • Patient has received or is receiving hormonal treatment (orchiectomy, polyoestradiol phosphate, or gonadotropin-releasing hormone analogue with or without antiandrogen)
  • Metastatic disease with positive bone scan within 2 months before treatment with more than one cancer related lesion or with one painful cancer related lesion in the presence of increasing PSA levels as follows: PSA >5 ng/ml, with increases on at least 2 successive occasions at least 2 weeks apart.
  • Patient is referred to local field radiotherapy (EBR) for metastatic bone pain. The area to be treated (index site) should match the positive bone scan, local radiation area not exceeding 400 cm2
  • ECOG performance status: 0-2
  • Life expectancy: at least 3 months
  • Age more than 40 years
  • Laboratory requirements:

    • Hematology: Neutrophil count ≥1,5 x 109/L Platelet count at least ≥100 x109/L and stable Hemoglobin >100 g/l or 10 g/dL
    • Hepatic function: Bilirubin within normal institutional limits ASAT and ALAT <2,5 times upper limit of normal (ULN)
    • Renal function: Creatinine <1,5 times the ULN (i.e. NCI grade ≤1)
  • Patient is willing and able to comply with the protocol, and agrees to return to the hospital for follow-up visits and examinations
  • Patient has been fully informed about the study and has signed the informed consent form

Exclusion Criteria:

  • Has received an investigational drug in the 4 weeks before or is scheduled to receiving one during the planned treatment period
  • Has received chemo-, immunotherapy or external radiotherapy within weeks before study drug administration
  • Has started treatment with bisphosphonates within 3 months before administration of study drug.
  • Has previously received systemic radiotherapy with strontium, samarium or rhenium
  • Change in hormonal therapy within the last 6 weeks before study drug administration
  • Other currently active (relapse within the last 3 year) malignancy (except nonmelanoma skin cancer) or known brain, liver, lung, visceral and lymphatic metastases dominating the clinical picture of the patient
  • Has received blood transfusion within last month
  • Other serious illness or medical condition as follows:

    • any uncontrolled infection
    • heart insufficiency, grade 3 or 4 as specified in NCI-CTC criteria
    • grade 2 or greater motor or sensory neuropathy
    • Crohn's disease or Ulcerative colitis 9) Known non-pathological bone fracture within the last two months

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00459654

Linköping, Sweden
Sundsvall, Sweden
United Kingdom
Nottingham, United Kingdom
Sponsors and Collaborators

Additional Information:
Responsible Party: Bayer Identifier: NCT00459654     History of Changes
Other Study ID Numbers: 15280
BC1-02 ( Other Identifier: Algeta ASA )
First Posted: April 12, 2007    Key Record Dates
Last Update Posted: June 25, 2014
Last Verified: June 2014

Keywords provided by Bayer:
Recurrent Prostate Cancer
Metastatic Cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Neoplasm Metastasis
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Neoplastic Processes
Pathologic Processes
Radium Ra 223 dichloride
Antineoplastic Agents