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

NCT00459654 | Completed Phase 2

• 2 other identifiers: 15280BC1-02
• Study Type: interventional
• Target: 64
• Locations: 2 countries
• Sites: 3

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.

Conditions

Prostate Cancer; Neoplasm Metastasis

Keywords

HRPC; Recurrent Prostate Cancer; Metastatic Cancer

Outcome Measures

Primary Outcomes (2)

• 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

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

  Up to 12 Month

Secondary Outcomes (9)

• Number of SREs per patient

  Up to 12 Month

• Changes in the levels of biochemical markers of bone formation

  Up to 12 Month

• Change in Prostate Specific Antigen (PSA)

  Up to 12 Month

• Change in pain level

  Up to 12 Month

• Changes in analgesic use during study period

  Up to 12 Month

Study Arms (2)

Radium-223 dichloride (Xofigo, BAY88-8223)

EXPERIMENTAL

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)

Saline

PLACEBO COMPARATOR

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

Drug: Saline

Interventions

Radium-223 dichloride (BAY88-8223) DRUG

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

Radium-223 dichloride (Xofigo, BAY88-8223)

Saline DRUG

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

Saline

Eligibility Criteria

• Age: 40 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (3)

Unknown Facility

Linköping, Sweden

Location

Unknown Facility

Sundsvall, Sweden

Location

Unknown Facility

Nottingham, United Kingdom

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis

Interventions

radium Ra 223 dichloride; Sodium Chloride

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2007
• First Posted: April 12, 2007
• Study Start: February 1, 2004
• Primary Completion: May 1, 2006
• Study Completion: May 1, 2007
• Last Updated: June 25, 2014

Record last verified: 2014-06

Locations

SE (2); GB (1)