check_circleStudy Completed

Prostatic Neoplasms

Standard dose versus high dose and versus extended standard dose radium-223 dichloride in castration-resistant prostate cancer metastatic to the bone

Trial purpose

This study will assess different doses and regimens of radium-223 dichloride on the incidence of symptomatic skeletal events. Eligible subjects must have castration resistant prostate cancer with 2 or more skeletal metastases documented within 8 weeks of randomization. Subjects will be randomized to one of 3 treatment arms in a 1:1:1 fashion: a standard regimen of radium-223 dichloride of 50 kBq/kg (55 kBq/kg after implementation of NIST update) injections every month for 6 months, a high dose regimen of 80 kBq/kg (88 kBq/kg after implementation of NIST update)injections every month for 6 months or an extended duration regimen of 50 kBq/kg (55 kBq/kg after implementation of NIST update) injections every month for 12 months. Following the treatment phase, subjects will be followed up every 12 weeks for a minimum of 2 years, at which point they will enter a long term follow-up period during which they are seen every 6 months for up to 7 years after the last dose of radium dichloride. Symptomatic skeletal event and safety endpoints will be assessed at each clinic visit. Pain and analgesic use data will be collected every 4 weeks through Week 48. Additionally, radiological assessments including MRI/CT of the abdomen and pelvis and chest CT, as well as technetium-99 bone scans will be performed at Weeks 8, 16, and 24 and continue every 12 weeks thereafter until disease progression is documented in either the bone or in soft tissue. Radiological imaging will be evaluated by blinded central review.

Key Participants Requirements

Sex

Male

Age

18 - N/A
  • - Histologically or cytologically confirmed adenocarcinoma of the prostate
    - Castration-resistant disease defined as:
     -- Serum testosterone level: ≤ 50 ng/dL (1.7 nmol/L)
     -- Bilateral orchiectomy or maintenance on androgen ablation therapy with luteinizing-hormone-releasing hormone (LHRH) agonist or antagonist, or polyestradiol phosphate
     -- Serum PSA (Prostate specific antigen) progression defined as 2 subsequent increases in PSA over a previous reference value (a minimum of 2 ng/mL [μg/L]) OR
     -- Radiographic evidence of disease progression in bone (according to Prostate Cancer Clinical Trials Working Group 2 [PCWG2] criteria) with or without PSA progression
    - Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 2. In case of ECOG PS 2, the PS has to be due to metastatic prostate cancer to the bone.
    - Two or more skeletal metastases (≥ 2 hot spots) on bone scintigraphy within 8 weeks of randomization
  • - History of visceral metastasis, or visceral metastases
    - Lymphadenopathy with lymph nodes exceeding 3 cm in short axis diameter
    - Central nervous system (CNS) metastases
    - Treatment with cytotoxic chemotherapy for prostate cancer within the previous 4 weeks prior to randomization, or planned treatment with cytotoxic chemotherapy agents for prostate cancer during the treatment period or follow-up
    - Chronic conditions associated with non-malignant abnormal bone growth (e.g. confirmed Paget's disease of bone)
    - Prior treatment with radium-223 dichloride
    - Prior systemic radiotherapy and hemibody external radiotherapy

Trial summary

Enrollment Goal
391
Trial Dates
March 2014 - August 2018
Phase
Phase 2
Could I Receive a placebo
No
Products
Xofigo (Radium-223 dichloride, BAY88-8223)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
München, 81675, Germany
Withdrawn
Ulm, 89081, Germany
Completed
Tübingen, 72076, Germany
Completed
Dresden, 01307, Germany
Withdrawn
Belfast, BT9 7AB, United Kingdom
Completed
Scottsdale, 85260, United States
Completed
Rockville, 20850, United States
Withdrawn
Seattle, 98109, United States
Completed
Bethesda, 20889, United States
Completed
St. Louis, 63110, United States
Completed
Detroit, 48201, United States
Completed
Pittsburgh, 15215, United States
Completed
Roma, 00152, Italy
Withdrawn
Reggio Emilia, 42123, Italy
Withdrawn
Pisa, 56126, Italy
Withdrawn
Genova, 16128, Italy
Withdrawn
Milano, 20162, Italy
Completed
Göteborg, 413 45, Sweden
Completed
Sundsvalls, 851 86, Sweden
Completed
Umeå, 901 85, Sweden
Completed
Beer Sheva, 8410101, Israel
Completed
Petah Tikva, 4941492, Israel
Completed
Jerusalem, 9112001, Israel
Completed
Haifa, 3109601, Israel
Completed
Kfar Saba, 4428164, Israel
Completed
Ramat Gan, 5262000, Israel
Completed
Adelaide, 5000, Australia
Completed
Melbourne, 3052, Australia
Completed
Darlinghurst, 2010, Australia
Completed
BOX HILL, 3128, Australia
Terminated
Irmandade Santa Casa de Misericordia de Porto AlegrePorto Alegre, 90470 340, Brazil
Terminated
Hospital Israelita Albert EinsteinSão Paulo, 05651-901, Brazil
Terminated
Hospital de Clínicas de Porto AlegrePorto Alegre, Brazil
Terminated
Instituto do Câncer do Estado de São PauloSão Paulo, 01246-000, Brazil
Withdrawn
HUS, 00029, Finland
Withdrawn
Seinäjoki, 60220, Finland
Withdrawn
Erlangen, 91054, Germany
Completed
Bebington, CH63 4JY, United Kingdom
Completed
Meldola, 47014, Italy
Withdrawn
Bari, 70124, Italy
Withdrawn
Padova, 35128, Italy
Withdrawn
Cordoba, 14004, Spain
Completed
Barcelona, 08025, Spain
Completed
Palma de Mallorca, 07120, Spain
Completed
Madrid, 28041, Spain
Completed
Pamplona, 31008, Spain
Completed
Hospitalet de Llobregat, 08907, Spain
Completed
Westmead, 2145, Australia
Completed
Seoul, 06273, Korea, Republic Of
Completed
Seoul, 06591, Korea, Republic Of
Completed
Seoul, 120-752, Korea, Republic Of
Completed
Seoul, 05505, Korea, Republic Of
Withdrawn
Manchester, M20 4BX, United Kingdom
Withdrawn
Usti nad Labem, 401 13, Czech Republic
Completed
Chomutov, 430 12, Czech Republic
Completed
Praha 5, 150 06, Czech Republic
Withdrawn
Praha 2, 128 08, Czech Republic
Completed
Ann Arbor, 48109-0330, United States
Withdrawn
Gliwice, 44-101, Poland
Withdrawn
Krakow, 31-501, Poland
Completed
Torino, 10043, Italy
Completed
Toronto, M4N 3M5, Canada
Completed
Santiago, 7500921, Chile
Completed
Busan, 49241, Korea, Republic Of
Completed
Taipei City, 112, Taiwan
Completed
Guishan Township, 333, Taiwan
Completed
Kaohsiung, 81362, Taiwan
Completed
Northwood, HA6 2RN, United Kingdom
Completed
Taunton, TA1 5DA, United Kingdom
Completed
Karlstad, 652 30, Sweden
Completed
Ottawa, K1H 8L6, Canada
Completed
Toronto, M5G 2M9, Canada
Completed
Taipei, 100, Taiwan
Completed
Taichung, 40705, Taiwan
Completed
Montreal, H2L 4M1, Canada
Withdrawn
New Hyde Park, 11040-1496, United States
Completed
Fort Myers, 33907, United States
Completed
Omaha, 68130, United States
Completed
New Haven, 06520, United States
Withdrawn
PARIS CEDEX 15, 75908, France
Completed
VILLEJUIF CEDEX, 94805, France
Completed
NANTES, 44805, France
Withdrawn
POITIERS, 86021, France
Withdrawn
SAINT-CLOUD, 92210, France
Completed
Portland, 97239, United States
Completed
East Setauket, 11733, United States
Completed
Vandoeuvre les Nancy, 54500, France
Completed
Arezzo, 52100, Italy
Terminated
IBCC - Instituto Brasileiro de Controle do CancerSão Paulo, 03102 002, Brazil
Withdrawn
Barcelona, 08035, Spain
Withdrawn
Seattle, 98101, United States
Completed
London, N6A 4L6, Canada

Primary Outcome

  • Symptomatic skeletal event-free survival
    date_rangeTime Frame:
    From randomization up to a maximum of 8 years, assessed every month during treatment and every 12 weeks during active follow-up
    enhanced_encryption
    Safety Issue:
    No

Secondary Outcome

  • Overall Survival
    date_rangeTime Frame:
    From randomization up to a maximum of 8 years, assessed every month during treatment and every 12 weeks during active follow-up and every 6 months in long term follow-up
    enhanced_encryption
    Safety Issue:
    No
  • Time to first symptomatic skeletal event
    date_rangeTime Frame:
    From randomization up to a maximum of 8 years, assessed every month during treatment and every 12 weeks during active follow-up
    enhanced_encryption
    Safety Issue:
    No
  • Radiological progression free survival
    date_rangeTime Frame:
    From randomization up to a maximum of 3 years, assessed at Weeks 8, 16, and 24 and continue every 12 weeks thereafter until disease progression is documented in either the bone or in soft tissue
    enhanced_encryption
    Safety Issue:
    No
  • Time to radiological progression
    date_rangeTime Frame:
    From randomization up to a maximum of 3 years, assessed at Weeks 8, 16, and 24 and continue every 12 weeks thereafter until disease progression is documented in either the bone or in soft tissue
    enhanced_encryption
    Safety Issue:
    No
  • Pain improvement rate, defined as the number of subjects with pain improvement divided by the total number of subjects evaluable for pain improvement
    Assessed by Worst Pain Score (WPS) on the Brief Pain Inventory Short Form (BPI-SF)
    date_rangeTime Frame:
    Up to 48 weeks
    enhanced_encryption
    Safety Issue:
    No
  • Time to pain progression
    Assessed by Worst Pain Score (WPS) on the Brief Pain Inventory Short Form (BPI-SF)
    date_rangeTime Frame:
    Up to 48 weeks
    enhanced_encryption
    Safety Issue:
    No
  • Number of participants with treatment-emergent adverse events or serious adverse events as a measure of safety and tolerability
    Includes acute and long-term safety, myelo suppression and additional primary malignancies
    date_rangeTime Frame:
    From randomization up to 8 years
    enhanced_encryption
    Safety Issue:
    Yes
  • Change in 24-hour analgesic use
    date_rangeTime Frame:
    Up to 48 weeks
    enhanced_encryption
    Safety Issue:
    No

Trial design

A three arm randomized, open-label Phase II study of radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) versus 80 kBq/kg (88 kBq/kg after implementation of NIST update), and versus 50 kBq/kg (55 kBq/kg after implementation of NIST update) in an extended dosing schedule in subjects with castration-resistant prostate cancer metastatic to the bone
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Randomized
Blinding
Open Label
Assignment
Parallel Assignment
Trial Arms
3