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

NCT02023697 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 165072013-003118-42
• Study Type: interventional
• Target: 391
• Locations: 15 countries
• Sites: 68

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

Outcome Measures

Primary Outcomes (6)

• Number of Participants With an Event Defining SSE Free Survival - High Dose vs. Standard Dose

  Symptomatic skeletal event (SSE) free survival is based on the following events: the use of external beam radiotherapy (EBRT) to relieve skeletal symptoms; the occurrence of new symptomatic pathological bone fractures (vertebral or nonvertebral); the occurrence of spinal cord compression; a tumor related orthopedic surgical intervention, and death. In this evaluation - comparison 1, SSE-FS following randomization is defined in ITT participants as the time from randomization to an SSE or death, whichever occurs first.

  From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization)

• Symptomatic Skeletal Event-Free Survival - High Dose vs. Standard Dose

  In this evaluation - comparison 1, SSE-FS following randomization is defined in ITT participants as the time from randomization to an SSE or death, whichever occurs first.

  From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization)

• Number of Participants With an Event Defining SSE Free Survival - Extended Dose vs. Standard Dose

  Symptomatic skeletal event (SSE) free survival is based on the following events: the use of external beam radiotherapy (EBRT) to relieve skeletal symptoms; the occurrence of new symptomatic pathological bone fractures (vertebral or nonvertebral); the occurrence of spinal cord compression; a tumor related orthopedic surgical intervention, and death. In this evaluation - Comparison 2, SSE-FS from 6th dose is defined in W24 participants as the time from Week 24 baseline (the 6th dose date) to an SSE or death, whichever occurs first.

  From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization)

• Symptomatic Skeletal Event-Free Survival - Extended Dose vs. Standard Dose

  In this evaluation - Comparison 2, SSE-FS from 6th dose is defined in W24 participants as the time from Week 24 baseline (the 6th dose date) to an SSE or death, whichever occurs first.

  From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization)

• Number of Participants With an Event Defining SSE Free Survival - Three Dose Groups As Randomized

  Symptomatic skeletal event (SSE) free survival is based on the following events: the use of external beam radiotherapy (EBRT) to relieve skeletal symptoms; the occurrence of new symptomatic pathological bone fractures (vertebral or nonvertebral); the occurrence of spinal cord compression; a tumor related orthopedic surgical intervention, and death.

  From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization)

• Symptomatic Skeletal Event Free Survival - Three Dose Groups As Randomized

  Symptomatic skeletal event (SSE) is defined as follows: The use of external beam radiotherapy (EBRT) to relieve skeletal symptoms; The occurrence of new symptomatic pathological bone fractures (vertebral or nonvertebral); The occurrence of spinal cord compression; A tumor related orthopedic surgical intervention.

  From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization)

Secondary Outcomes (33)

• Number of Participants With an Overall Survival Event - High Dose vs. Standard Dose

  From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization)

• Overall Survival - High Dose vs. Standard Dose

  From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization)

• Number of Participants With an Overall Survival Event - Extended Dose vs. Standard Dose

  From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization)

• Overall Survival - Extended Dose vs. Standard Dose

  From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization)

• Number of Participants With an Overall Survival - Three Dose Groups As Randomized

  From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization)

Other Outcomes (1)

• Number of Participants With Change in Analgesic Use From Baseline to Worst Status Post-Baseline

  From randomization to 135 SSE-FS events have been observed in comparison 1 or 75 SSE-FS events observed in comparison 2, whichever occurred last (approximately 36 months from first patient randomization)

Study Arms (3)

Radium-223 dichloride (Standard dose)

EXPERIMENTAL

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).

Drug: Radium-223 dichloride (Xofigo, BAY88-8223)

Radium-223 dichloride (High dose)

EXPERIMENTAL

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).

Drug: Radium-223 dichloride (Xofigo, BAY88-8223)

Radium-223 dichloride (Extended standard dose)

EXPERIMENTAL

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).

Drug: Radium-223 dichloride (Xofigo, BAY88-8223)

Interventions

Radium-223 dichloride (Xofigo, BAY88-8223) DRUG

Radium-223 dichloride (Extended standard dose); Radium-223 dichloride (High dose); Radium-223 dichloride (Standard dose)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (68)

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Scottsdale, Arizona, 85260, United States

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New Haven, Connecticut, 06520, United States

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Fort Myers, Florida, 33907, United States

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Bethesda, Maryland, 20889, United States

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Rockville, Maryland, 20850, United States

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Ann Arbor, Michigan, 48109-0330, United States

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Detroit, Michigan, 48201, United States

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St Louis, Missouri, 63110, United States

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Omaha, Nebraska, 68130, United States

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East Setauket, New York, 11733, United States

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Portland, Oregon, 97239, United States

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Pittsburgh, Pennsylvania, 15215, United States

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Adelaide, South Australia, 5000, Australia

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Melbourne, Victoria, 3052, Australia

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Box Hill, 3128, Australia

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Darlinghurst, 2010, Australia

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Westmead, 2145, Australia

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Irmandade Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90470 340, Brazil

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Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

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Instituto do Câncer do Estado de São Paulo

São Paulo, São Paulo, 01246-000, Brazil

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IBCC - Instituto Brasileiro de Controle do Cancer

São Paulo, São Paulo, 03102 002, Brazil

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Hospital Israelita Albert Einstein

São Paulo, São Paulo, 05651-901, Brazil

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London, Ontario, N6A 4L6, Canada

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Ottawa, Ontario, K1H 8L6, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Montreal, Quebec, H2L 4M1, Canada

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Santiago, 7500921, Chile

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Chomutov, 430 12, Czechia

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Prague, 150 06, Czechia

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Nantes, 44805, France

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Vandœuvre-lès-Nancy, 54500, France

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Villejuif, 94805, France

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Tübingen, Baden-Wurttemberg, 72076, Germany

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München, Bavaria, 81675, Germany

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Dresden, Saxony, 01307, Germany

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Beersheba, 8410101, Israel

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Haifa, 3109601, Israel

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Jerusalem, 9112001, Israel

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Kfar Saba, 4428164, Israel

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Petah Tikva, 4941492, Israel

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Ramat Gan, 5262000, Israel

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Meldola, Emilia-Romagna, 47014, Italy

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Rome, Lazio, 00152, Italy

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Turin, Piedmont, 10043, Italy

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Arezzo, Tuscany, 52100, Italy

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Busan, Busan Gwang''yeogsi, 49241, South Korea

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Seoul, Seoul Teugbyeolsi, 06273, South Korea

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Seoul, 05505, South Korea

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Seoul, 06591, South Korea

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Seoul, 120-752, South Korea

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L'Hospitalet de Llobregat, Barcelona, 08907, Spain

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Palma de Mallorca, Illes Baleares, 07120, Spain

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Barcelona, 08025, Spain

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Madrid, 28041, Spain

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Pamplona, 31008, Spain

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Gothenburg, 413 45, Sweden

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Karlstad, 652 30, Sweden

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Sundsvalls, 851 86, Sweden

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Umeå, 901 85, Sweden

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Taipei City, Taipei, 112, Taiwan

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Guishan Township, Taoyuan, 333, Taiwan

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Kaohsiung City, 81362, Taiwan

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Taichung, 40705, Taiwan

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Taipei, 100, Taiwan

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Bebington, Merseyside, CH63 4JY, United Kingdom

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Taunton, Somerset, TA1 5DA, United Kingdom

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Northwood, HA6 2RN, United Kingdom

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Related Publications (1)

• 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.

  PMID: 31959342 DERIVED

Related Links

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

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

radium Ra 223 dichloride

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer AG

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2013
• First Posted: December 30, 2013
• Study Start: March 10, 2014
• Primary Completion: March 1, 2017
• Study Completion: August 9, 2018
• Last Updated: July 12, 2019
• Results First Posted: July 12, 2018

Record last verified: 2019-06

Locations

CA (5); CZ (2); IT (4); CL (1); KR (5); FR (3); BR (5); DE (3); ES (5); TW (5); SE (4); GB (3); AU (5); US (12); IL (6)