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

Primary Purpose

Prostate Cancer, Neoplasm Metastasis

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Radium-223 dichloride (BAY88-8223)

Saline

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring HRPC, Recurrent Prostate Cancer, Metastatic Cancer

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Radium-223 dichloride (Xofigo, BAY88-8223)

Saline

Arm Description

Each subject receives local filed external beam radiotherapy (EBR) and repeated injections of the investigational drug radium-223 (EBR+Radium-223)

Each subject receives local filed external beam radiotherapy (EBR) and repeated injections of saline (EBR+placebo)

Outcomes

Primary Outcome Measures

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

Relative change (%) in bone-ALP levels from baseline to 4 weeks after last injection

Secondary Outcome Measures

Number of SREs per patient

Changes in the levels of biochemical markers of bone formation

Change in Prostate Specific Antigen (PSA)

Change in pain level

Changes in analgesic use during study period

Changes in Edmonton Symptom Assessment Scale (ESAS) from baseline

Overall survival

Adverse events

Clinical laboratory tests including haematology, renal and liver function parameters

Full Information

NCT ID

NCT00459654

First Posted

April 11, 2007

Last Updated

June 24, 2014

Sponsor

Bayer

1. Study Identification

Unique Protocol Identification Number

NCT00459654

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

June 2014

Overall Recruitment Status

Completed

Study Start Date

February 2004 (undefined)

Primary Completion Date

May 2006 (Actual)

Study Completion Date

May 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bayer

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer, Neoplasm Metastasis

Keywords

HRPC, Recurrent Prostate Cancer, Metastatic Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

64 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Radium-223 dichloride (Xofigo, BAY88-8223)

Arm Type

Experimental

Arm Description

Each subject receives local filed external beam radiotherapy (EBR) and repeated injections of the investigational drug radium-223 (EBR+Radium-223)

Arm Title

Saline

Arm Type

Placebo Comparator

Arm Description

Each subject receives local filed external beam radiotherapy (EBR) and repeated injections of saline (EBR+placebo)

Intervention Type

Drug

Intervention Name(s)

Radium-223 dichloride (BAY88-8223)

Intervention Description

Four Radium-223 injections were given at 4-weekly intervals starting after the first fraction of EBR.

Intervention Type

Drug

Intervention Name(s)

Saline

Intervention Description

Four Saline injections were given at 4-weekly intervals starting after the first fraction of EBR.

Primary Outcome Measure Information:

Title

Time to occurrence of Skeletal-related Events (SRE)

Description

Time Frame

Up to 12 Month

Title

Relative change (%) in bone-ALP levels from baseline to 4 weeks after last injection

Time Frame

Up to 12 Month

Secondary Outcome Measure Information:

Title

Number of SREs per patient

Time Frame

Up to 12 Month

Title

Changes in the levels of biochemical markers of bone formation

Time Frame

Up to 12 Month

Title

Change in Prostate Specific Antigen (PSA)

Time Frame

Up to 12 Month

Title

Change in pain level

Time Frame

Up to 12 Month

Title

Changes in analgesic use during study period

Time Frame

Up to 12 Month

Title

Changes in Edmonton Symptom Assessment Scale (ESAS) from baseline

Time Frame

Up to 12 Month

Title

Overall survival

Time Frame

up to 24 months

Title

Adverse events

Time Frame

up to 24 months

Title

Clinical laboratory tests including haematology, renal and liver function parameters

Time Frame

up to 24 months

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility 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

Facility Information:

City

Linköping

Country

Sweden

City

Sundsvall

Country

Sweden

City

Nottingham

Country

United Kingdom

12. IPD Sharing Statement

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

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