Study of Radium-223 Dichloride in Combination With Exemestane and Everolimus Versus Placebo in Combination With Exemestane and Everolimus in Subjects With Bone Predominant HER2 Negative Hormone Receptor Positive Metastatic Breast Cancer
NCT ID: NCT02258451
Last Updated: 2023-11-24
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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COMPLETED
PHASE2
283 participants
INTERVENTIONAL
2015-06-04
2022-10-28
Brief Summary
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After implementation of CSP Amendment 10, only a limited number of subjects will remain in this study, in order to reduce the burden to study subjects, collection of data will be reduced and will focus mainly on acute safety, SSE, and OS. Once subjects are rolled over, the long-term safety will be collected and assessed entirely in the separate extended safety follow-up study.
Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Radium-223 dichloride + exemestane/everolimus
Up to 6 cycles of radium-223 dichloride 50kBq/kg body weight (55 kBq/kg after implementation of National Institute of Standards and Technology \[NIST\] update) (randomized). Participants will also receive exemestane, 25-mg tablet once daily (after a meal), and everolimus, 10 mg once daily (with or without food), and supportive care as per the local or institutional standard of practice.
Radium-223 dichloride (Xofigo, BAY88-8223)
Up to 6 cycles of radium-223 dichloride 50kBq/kg body (55 kBq/kg after implementation of NIST update)
Exemestane
One 25 mg tablet once daily after a meal.
Everolimus
The recommended dose of everolimus administered in the study is 10 mg once daily with or without food.
Starting dose, dose modifications, and administration of exemestane and everolimus must be in compliance with the local labels in each of the participating countries and/or in line with local standard of practice.
Placebo + exemestane/everolimus
Up to 6 cycles of saline injection (placebo) (randomized). Participants will also receive exemestane, 25-mg tablet once daily (after a meal), and everolimus, 10 mg once daily (with or without food), and supportive care as per the local or institutional standard of practice.
Placebo (saline)
Up to 6 cycles of saline injection
Exemestane
One 25 mg tablet once daily after a meal.
Everolimus
The recommended dose of everolimus administered in the study is 10 mg once daily with or without food.
Starting dose, dose modifications, and administration of exemestane and everolimus must be in compliance with the local labels in each of the participating countries and/or in line with local standard of practice.
Interventions
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Radium-223 dichloride (Xofigo, BAY88-8223)
Up to 6 cycles of radium-223 dichloride 50kBq/kg body (55 kBq/kg after implementation of NIST update)
Placebo (saline)
Up to 6 cycles of saline injection
Exemestane
One 25 mg tablet once daily after a meal.
Everolimus
The recommended dose of everolimus administered in the study is 10 mg once daily with or without food.
Starting dose, dose modifications, and administration of exemestane and everolimus must be in compliance with the local labels in each of the participating countries and/or in line with local standard of practice.
Eligibility Criteria
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Inclusion Criteria
* Documentation of histological or cytological confirmation of estrogen receptor positive (ER+) and HER2 negative adenocarcinoma of the breast must be available.
* Documentation of menopausal status: postmenopausal subjects or pre-menopausal subjects with ovarian radiation or concomitant therapy with a luteinizing hormone-releasing hormone (LH-RH) agonist/antagonist are eligible.
* Subjects with bone dominant disease with at least 2 skeletal metastases identified at baseline by bone scintigraphy and confirmed by computed tomography (CT)/magnetic resonance imaging (MRI).
* Subjects must have received at least one line of hormonal therapy in the metastatic setting.
* Subjects who are eligible as per the Investigator's assessment and according to the local label for treatment with exemestane and everolimus as a second line or greater of hormone therapy in a metastatic setting.
* Subjects must have experienced recurrent/progressive disease following treatment with a non-steroidal aromatase inhibitor (letrozole or anastrozole) in an adjuvant or metastatic setting
* Subjects must have experienced no more than two skeletal-related events (SREs) prior to study entry defined as: need for external beam radiotherapy (EBRT) to bone pain, pathological bone fracture (excluding major trauma), spinal cord compression and/or orthopedic surgical procedure. Subjects with no prior SREs are not permitted.
* Subjects must be on therapy with bisphosphonates or denosumab for at least 1 month before start of study treatment.
* Adequate hematological, liver and kidney function.
Exclusion Criteria
* Patients with immediately life-threatening visceral disease for whom chemotherapy is preferred treatment option.
* Subjects who have either received chemotherapy for metastatic disease or are considered by the treating investigator to be appropriate candidates for chemotherapy as current treatment for metastatic breast cancer are excluded. Chemotherapy administered for adjuvant/neo adjuvant disease is acceptable provided it was administered at least 1 year prior to study entry.
* Subjects who received prior treatment or are already receiving everolimus treatment prior to study entry are not eligible.
* Subjects with known or history of brain metastases or leptomeningeal disease: subjects with neurological symptoms must undergo a contrast CT scan or MRI of the brain within 28 days prior to randomization to exclude active brain metastasis. Imaging of the central nervous system (CNS) is otherwise not required.
18 Years
FEMALE
No
Sponsors
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Bayer
INDUSTRY
Responsible Party
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Principal Investigators
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Bayer Study Director
Role: STUDY_DIRECTOR
Bayer
Locations
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La Jolla, California, United States
Los Angeles, California, United States
New Haven, Connecticut, United States
Hollywood, Florida, United States
Ashland, Kentucky, United States
Rockville, Maryland, United States
Ann Arbor, Michigan, United States
Detroit, Michigan, United States
Pontiac, Michigan, United States
Rochester, Minnesota, United States
St Louis, Missouri, United States
Newark, New Jersey, United States
Jamaica, New York, United States
Watertown, South Dakota, United States
Spokane, Washington, United States
Innsbruck, , Austria
Brussels, , Belgium
Edegem, , Belgium
Kortrijk, , Belgium
Leuven, , Belgium
Angers, , France
Nantes, , France
Nîmes, , France
Saint-Cloud, , France
Tours, , France
Herne, North Rhine-Westphalia, Germany
Chai Wan, , Hong Kong
Hong Kong, , Hong Kong
Kowloon, , Hong Kong
Afula, , Israel
Beersheba, , Israel
Haifa, , Israel
Holon, , Israel
Jerusalem, , Israel
Jerusalem, , Israel
Ramat Gan, , Israel
Tel Aviv, , Israel
Zrifin, , Israel
Bari, Apulia, Italy
Bologna, Emilia-Romagna, Italy
Forlì Cesena, Emilia-Romagna, Italy
Modena, Emilia-Romagna, Italy
Rome, Lazio, Italy
Rome, Lazio, Italy
Genoa, Liguria, Italy
Cremona, Lombardy, Italy
Milan, Lombardy, Italy
Pisa, Tuscany, Italy
Nagoya, Aichi-ken, Japan
Sapporo, Hokkaido, Japan
Sayama, Osaka, Japan
Hidaka, Saitama, Japan
Kita-Adachigun, Saitama, Japan
Koto-ku, Tokyo, Japan
Kagoshima, , Japan
Osaka, , Japan
Oslo, , Norway
Bialystok, , Poland
Gdansk, , Poland
Gdynia, , Poland
Poznan, , Poland
Warsaw, , Poland
Singapore, , Singapore
Singapore, , Singapore
Singapore, , Singapore
Suwon, Gyeonggido, South Korea
Seoul, Seoul Teugbyeolsi, South Korea
Busan, , South Korea
Daegu, , South Korea
Incheon, , South Korea
Seoul, , South Korea
Palma de Mallorca, Illes Baleares, Spain
Barcelona, , Spain
Barcelona, , Spain
Barcelona, , Spain
Madrid, , Spain
Madrid, , Spain
Madrid, , Spain
Madrid, , Spain
Pamplona, , Spain
Seville, , Spain
Seville, , Spain
Aarau, Canton of Aargau, Switzerland
Kaohsiung City, , Taiwan
Taichung, , Taiwan
Taipei, , Taiwan
Taipei, , Taiwan
Truro, Cornwall, United Kingdom
Plymouth, Devon, United Kingdom
Nottingham, Nottinghamshire, United Kingdom
Taunton, Somerset, United Kingdom
Bristol, , United Kingdom
Countries
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References
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Rugo HS, Van Poznak CH, Neven P, Danielewicz I, Lee SC, Campone M, Chik JYK, Vega Alonso E, Naume B, Brain E, Siegel JM, Li R, Uema D, Wagner VJ, Coleman RE. Radium-223 in women with hormone receptor-positive bone-metastatic breast cancer receiving endocrine therapy: pooled analysis of two international, phase 2, randomized, double-blind, placebo-controlled trials. Breast Cancer Res Treat. 2024 Apr;204(2):249-259. doi: 10.1007/s10549-023-07147-z. Epub 2023 Dec 20.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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Click here to find information about studies related to Bayer Healthcare products conducted in Europe
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Other Identifiers
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2014-002114-23
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
17096
Identifier Type: -
Identifier Source: org_study_id