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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00459654
First received: April 11, 2007
Last updated: June 24, 2014
Last verified: June 2014
  Purpose

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 Intervention Phase
Prostate Cancer
Neoplasm Metastasis
Drug: Radium-223 dichloride (BAY88-8223)
Drug: Saline
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Time to occurrence of Skeletal-related Events (SRE) [ Time Frame: Up to 12 Month ] [ Designated as safety issue: No ]
    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

  • Relative change (%) in bone-ALP levels from baseline to 4 weeks after last injection [ Time Frame: Up to 12 Month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of SREs per patient [ Time Frame: Up to 12 Month ] [ Designated as safety issue: No ]
  • Changes in the levels of biochemical markers of bone formation [ Time Frame: Up to 12 Month ] [ Designated as safety issue: No ]
  • Change in Prostate Specific Antigen (PSA) [ Time Frame: Up to 12 Month ] [ Designated as safety issue: No ]
  • Change in pain level [ Time Frame: Up to 12 Month ] [ Designated as safety issue: No ]
  • Changes in analgesic use during study period [ Time Frame: Up to 12 Month ] [ Designated as safety issue: No ]
  • Changes in Edmonton Symptom Assessment Scale (ESAS) from baseline [ Time Frame: Up to 12 Month ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: up to 24 months ] [ Designated as safety issue: Yes ]
  • Adverse events [ Time Frame: up to 24 months ] [ Designated as safety issue: Yes ]
  • Clinical laboratory tests including haematology, renal and liver function parameters [ Time Frame: up to 24 months ] [ Designated as safety issue: Yes ]

Enrollment: 64
Study Start Date: February 2004
Study Completion Date: May 2007
Primary Completion Date: May 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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
  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00459654

Locations
Sweden
Linköping, Sweden
Sundsvall, Sweden
United Kingdom
Nottingham, United Kingdom
Sponsors and Collaborators
Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00459654     History of Changes
Other Study ID Numbers: 15280, BC1-02
Study First Received: April 11, 2007
Last Updated: June 24, 2014
Health Authority: Norway: Norwegian Medicines Agency
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Bayer:
HRPC
Recurrent Prostate Cancer
Metastatic Cancer

Additional relevant MeSH terms:
Neoplasm Metastasis
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Neoplastic Processes
Pathologic Processes
Prostatic Diseases
Urogenital Neoplasms
Succinylcholine
Neuromuscular Agents
Neuromuscular Blocking Agents
Neuromuscular Depolarizing Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014