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

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00459654
• Other study ID #: 15280
• Secondary ID: BC1-02
• Status: Completed
• Phase: Phase 2
• First received: April 11, 2007
• Last updated: June 24, 2014
• Start date: February 2004
• Est. completion date: May 2007

Study information

• Verified date: June 2014
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Norway: Norwegian Medicines AgencySweden: Medical Products AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: May 2007
• Est. primary completion date: May 2006
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasm Metastasis
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Radium-223 dichloride (BAY88-8223)
Four Radium-223 injections were given at 4-weekly intervals starting after the first fraction of EBR.
• Saline
Four Saline injections were given at 4-weekly intervals starting after the first fraction of EBR.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to occurrence of Skeletal-related Events (SRE)	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	Up to 12 Month	No
Primary	Relative change (%) in bone-ALP levels from baseline to 4 weeks after last injection		Up to 12 Month	No
Secondary	Number of SREs per patient		Up to 12 Month	No
Secondary	Changes in the levels of biochemical markers of bone formation		Up to 12 Month	No
Secondary	Change in Prostate Specific Antigen (PSA)		Up to 12 Month	No
Secondary	Change in pain level		Up to 12 Month	No
Secondary	Changes in analgesic use during study period		Up to 12 Month	No
Secondary	Changes in Edmonton Symptom Assessment Scale (ESAS) from baseline		Up to 12 Month	No
Secondary	Overall survival		up to 24 months	Yes
Secondary	Adverse events		up to 24 months	Yes
Secondary	Clinical laboratory tests including haematology, renal and liver function parameters		up to 24 months	Yes

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