Standard Dose Versus High Dose and Versus Extended Standard Dose Radium-223 Dichloride in Castration-resistant Prostate Cancer Metastatic to the Bone

NCT ID: NCT02023697

Last Updated: 2019-07-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 391 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-10
• Study Completion Date: 2018-08-09

Brief Summary

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.

Conditions

Prostatic Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Radium-223 dichloride (Standard dose)

One injection to be administered every 4 weeks up to 6 injections. The dose per injection is 50 kBq/kg body weight (55 kBq/kg after implementation of NIST update).

Group Type: EXPERIMENTAL

Radium-223 dichloride (Xofigo, BAY88-8223)

Intervention Type: DRUG

Radium-223 dichloride (High dose)

One injection to be administered every 4 weeks up to 6 injections. The dose per injection is 80 kBq/kg body weight (88 kBq/kg after implementation of NIST update).

Group Type: EXPERIMENTAL

Radium-223 dichloride (Xofigo, BAY88-8223)

Intervention Type: DRUG

Radium-223 dichloride (Extended standard dose)

One injection to be administered every 4 weeks up to 12 injections. The dose per injection is 50 kBq/kg body weight (55 kBq/kg after implementation of NIST update).

Group Type: EXPERIMENTAL

Radium-223 dichloride (Xofigo, BAY88-8223)

Intervention Type: DRUG

Interventions

Radium-223 dichloride (Xofigo, BAY88-8223)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Scottsdale, Arizona, United States

New Haven, Connecticut, United States

Fort Myers, Florida, United States

Bethesda, Maryland, United States

Rockville, Maryland, United States

Ann Arbor, Michigan, United States

Detroit, Michigan, United States

St Louis, Missouri, United States

Omaha, Nebraska, United States

East Setauket, New York, United States

Portland, Oregon, United States

Pittsburgh, Pennsylvania, United States

Adelaide, South Australia, Australia

Melbourne, Victoria, Australia

Box Hill, , Australia

Darlinghurst, , Australia

Westmead, , Australia

Irmandade Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Instituto do Câncer do Estado de São Paulo

São Paulo, São Paulo, Brazil

IBCC - Instituto Brasileiro de Controle do Cancer

São Paulo, São Paulo, Brazil

Hospital Israelita Albert Einstein

São Paulo, São Paulo, Brazil

London, Ontario, Canada

Ottawa, Ontario, Canada

Toronto, Ontario, Canada

Toronto, Ontario, Canada

Montreal, Quebec, Canada

Santiago, , Chile

Chomutov, , Czechia

Prague, , Czechia

Nantes, , France

Vandœuvre-lès-Nancy, , France

Villejuif, , France

Tübingen, Baden-Wurttemberg, Germany

München, Bavaria, Germany

Dresden, Saxony, Germany

Beersheba, , Israel

Haifa, , Israel

Jerusalem, , Israel

Kfar Saba, , Israel

Petah Tikva, , Israel

Ramat Gan, , Israel

Meldola, Emilia-Romagna, Italy

Rome, Lazio, Italy

Turin, Piedmont, Italy

Arezzo, Tuscany, Italy

Busan, Busan Gwang''yeogsi, South Korea

Seoul, Seoul Teugbyeolsi, South Korea

Seoul, , South Korea

Seoul, , South Korea

Seoul, , South Korea

L'Hospitalet de Llobregat, Barcelona, Spain

Palma de Mallorca, Illes Baleares, Spain

Barcelona, , Spain

Madrid, , Spain

Pamplona, , Spain

Gothenburg, , Sweden

Karlstad, , Sweden

Sundsvalls, , Sweden

Umeå, , Sweden

Taipei City, Taipei, Taiwan

Guishan Township, Taoyuan, Taiwan

Kaohsiung City, , Taiwan

Taichung, , Taiwan

Taipei, , Taiwan

Bebington, Merseyside, United Kingdom

Taunton, Somerset, United Kingdom

Northwood, , United Kingdom

Countries

United States; Australia; Brazil; Canada; Chile; Czechia; France; Germany; Israel; Italy; South Korea; Spain; Sweden; Taiwan; United Kingdom

References

Sternberg CN, Saad F, Graff JN, Peer A, Vaishampayan UN, Leung E, Rosenbaum E, Gurney H, Epstein RJ, Davis ID, Wu B, Trandafir L, Wagner VJ, Hussain M. A randomised phase II trial of three dosing regimens of radium-223 in patients with bone metastatic castration-resistant prostate cancer. Ann Oncol. 2020 Feb;31(2):257-265. doi: 10.1016/j.annonc.2019.10.025. Epub 2019 Dec 23.

Reference Type: DERIVED

PMID: 31959342 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.bayer.com/

Click here to find results for studies related to Bayer Healthcare products.

Other Identifiers

2013-003118-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

16507

Identifier Type: -

Identifier Source: org_study_id