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Study of Radium-223 Dichloride Versus Placebo and Treatment With Exemestane / Everolimus in Subjects With Bone Predominant HER2 (Human Epidermal Growth Factor Receptor 2) Negative Hormone Receptor Positive Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT02258451
Recruitment Status : Active, not recruiting
First Posted : October 7, 2014
Last Update Posted : April 4, 2019
Sponsor:
Information provided by (Responsible Party):
Bayer

Brief Summary:
The objective of this study is to assess efficacy and safety of radium 223 dichloride in subjects with human epidermal growth factor receptor 2 (HER2) negative hormone receptor positive breast cancer with bone metastases treated with exemestane and everolimus.

Condition or disease Intervention/treatment Phase
Breast Neoplasms Drug: Radium-223 dichloride (Xofigo, BAY88-8223) Drug: Placebo (saline) Drug: Exemestane Drug: Everolimus Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 283 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II Randomized, Double-blind, Placebo-controlled Trial of Radium-223 Dichloride in Combination With Exemestane and Everolimus Versus Placebo in Combination With Exemestane and Everolimus When Administered to Metastatic HER2 Negative Hormone Receptor Positive Breast Cancer Subjects With Bone Metastases
Actual Study Start Date : June 4, 2015
Estimated Primary Completion Date : July 31, 2019
Estimated Study Completion Date : August 30, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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) + All patients will receive exemestane and everolimus
Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
Up to 6 cycles of radium-223 dichloride 50kBq/kg body (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update)

Drug: Exemestane
25 mg once daily with or without food Dosage and administration of exemestane must be in compliance with the local labels in each of the participating countries and in line with standard practice guidelines.

Drug: Everolimus
10 mg tablet once daily after a meal Dosage and administration of everolimus must be in compliance with the local labels in each of the participating countries and in line with standard practice guidelines.

Placebo Comparator: Placebo + exemestane/everolimus
Up to 6 cycles of saline injection (placebo) (randomized) + All patients will receive exemestane and everolimus
Drug: Placebo (saline)
Up to 6 cycles of saline injection

Drug: Exemestane
25 mg once daily with or without food Dosage and administration of exemestane must be in compliance with the local labels in each of the participating countries and in line with standard practice guidelines.

Drug: Everolimus
10 mg tablet once daily after a meal Dosage and administration of everolimus must be in compliance with the local labels in each of the participating countries and in line with standard practice guidelines.




Primary Outcome Measures :
  1. Symptomatic skeletal event free survival (SSE-FS). [ Time Frame: From time of randomization up to 26 months ]

Secondary Outcome Measures :
  1. Overall survival [ Time Frame: From time of randomization up to 26 months ]
  2. Time to opiate use for cancer pain [ Time Frame: From time of randomization up to 26 months ]
  3. Time to pain progression (only in subjects with baseline worst pain score (WPS) ≤8) [ Time Frame: From time of randomization up to 26 months ]
  4. Time to cytotoxic chemotherapy [ Time Frame: From time of randomization up to 26 months ]
  5. Radiological progression-free survival (rPFS) [ Time Frame: From time of randomization up to 26 months ]
  6. Frequency of abnormalities in laboratory examinations [ Time Frame: From time of randomization up to 26 months ]
  7. Pain improvement rate [ Time Frame: From time of randomization up to 26 months ]
  8. To measure new primary malignancies and hematopoietic reserve for tolerability of subsequent chemotherapy [ Time Frame: From time of randomization up to 26 months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women (≥18 years of age) with metastatic breast cancer not amenable to curative treatment by surgery or radiotherapy.
  • 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:

  • Subjects with Inflammatory breast cancer.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02258451


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Locations
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United States, Arizona
Yuma, Arizona, United States, 85364
United States, California
La Jolla, California, United States, 92093
Long Beach, California, United States, 90813
Los Angeles, California, United States, 90033
San Francisco, California, United States, 94117
United States, Connecticut
New Haven, Connecticut, United States, 06510
United States, Florida
Hollywood, Florida, United States, 33021
United States, Kentucky
Ashland, Kentucky, United States, 41101
United States, Maryland
Rockville, Maryland, United States, 20850
United States, Michigan
Ann Arbor, Michigan, United States, 48109
Detroit, Michigan, United States, 48202
Pontiac, Michigan, United States, 48341
United States, Minnesota
Rochester, Minnesota, United States, 55905
United States, Missouri
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Newark, New Jersey, United States, 07103
United States, New York
Jamaica, New York, United States, 11432
Lake Success, New York, United States, 11042
United States, South Dakota
Watertown, South Dakota, United States, 57201
United States, Washington
Spokane, Washington, United States, 99208-1129
Austria
Innsbruck, Austria, 6020
Belgium
Bruxelles - Brussel, Belgium, 1000
Edegem, Belgium, 2650
Kortrijk, Belgium, 8500
Leuven, Belgium, 3000
China, Guangdong
Guangzhou, Guangdong, China, 510060
Guangzhou, Guangdong, China, 510080
China, Jiangsu
Nanjing, Jiangsu, China, 210009
China
Beijing, China, 100050
Beijing, China, 100730
Czechia
Chomutov, Czechia, 430 12
Olomouc, Czechia, 775 20
Ostrava, Czechia, 708 52
Praha 2, Czechia, 12808
France
Angers Cedex, France, 49933
Nantes, France, 44805
Nimes, France, 30029
Saint Cloud, France, 92210
Tours, France, 37044
Germany
Tübingen, Baden-Württemberg, Germany, 72076
Bonn, Nordrhein-Westfalen, Germany, 53105
Essen, Nordrhein-Westfalen, Germany, 45147
Herne, Nordrhein-Westfalen, Germany, 44625
Münster, Nordrhein-Westfalen, Germany, 48149
Mainz, Rheinland-Pfalz, Germany, 55131
Hong Kong
Chai wan, Hong Kong
Kowloon, Hong Kong
New Territories, Hong Kong
Israel
Afula, Israel, 1834111
Beer Sheva, Israel, 8410101
Haifa, Israel, 3109601
Holon, Israel, 5810001
Jerusalem, Israel, 9103102
Jerusalem, Israel, 9112001
Ramat Gan, Israel, 5262000
Tel Aviv, Israel, 64239
Zerifin, Israel, 6093000
Italy
Bologna, Emilia-Romagna, Italy, 40138
Meldola, Emilia-Romagna, Italy, 47014
Modena, Emilia-Romagna, Italy, 41124
Reggio Emilia, Emilia-Romagna, Italy, 42123
Roma, Lazio, Italy, 00144
Roma, Lazio, Italy, 00149
Roma, Lazio, Italy, 00161
Roma, Lazio, Italy, 00189
Genova, Liguria, Italy, 16128
Cremona, Lombardia, Italy, 26100
Milano, Lombardia, Italy, 20132
Milano, Lombardia, Italy, 20141
Bari, Puglia, Italy, 70124
Palermo, Sicilia, Italy, 90146
Pisa, Toscana, Italy, 56126
Padova, Veneto, Italy, 35128
Verona, Veneto, Italy, 37024
Japan
Nagoya, Aichi, Japan, 464-8681
Sapporo, Hokkaido, Japan, 060-8648
Osakasayama, Osaka, Japan, 589-8511
Hidaka, Saitama, Japan, 350-1298
Kita-Adachigun, Saitama, Japan, 362-0806
Koto-ku, Tokyo, Japan, 135-8550
Kagoshima, Japan, 892-0833
Kagoshima, Japan, 892-0838
Osaka, Japan, 540-0006
Korea, Republic of
Suwon-si, Gyeonggido, Korea, Republic of, 442-723
Busan, Korea, Republic of, 49241
Daegu, Korea, Republic of, 41931
Incheon, Korea, Republic of
Seoul, Korea, Republic of, 03080
Seoul, Korea, Republic of, 05505
Norway
Oslo, Norway, 0424
Poland
Bialystok, Poland, 15-027
Gdansk, Poland, 80-952
Gdynia, Poland, 81-519
Poznan, Poland, 61-485
Warszawa, Poland, 02-781
Singapore
Singapore, Singapore, 119074
Singapore, Singapore, 169610
Singapore, Singapore, 258499
Spain
Palma de Mallorca, Illes Baleares, Spain, 07120
Barcelona, Spain, 08025
Barcelona, Spain, 08035
Barcelona, Spain, 08036
Madrid, Spain, 28033
Madrid, Spain, 28041
Madrid, Spain, 28046
Madrid, Spain, 28050
Pamplona, Spain, 31008
Sevilla, Spain, 41013
Sevilla, Spain, 41071
Switzerland
Aarau, Aargau, Switzerland, 5001
Viganello, Ticino, Switzerland, 6962
Taiwan
Kaoshiung, Taiwan, 81346
Taichung, Taiwan, 40705
Taipei, Taiwan
United Kingdom
Truro, Cornwall, United Kingdom, TR1 3LJ
Plymouth, Devon, United Kingdom, PL6 8DH
Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
Taunton, Somerset, United Kingdom, TA1 5DA
Guildford, Surrey, United Kingdom, GU27XX
Coventry, West Midlands, United Kingdom, CV2 2DX
Belfast, United Kingdom, BT9 7AE
Bristol, United Kingdom, BS2 8ED
Cottingham, United Kingdom, HU16 5JQ
Merseyside, United Kingdom, CH63 4JY
Sponsors and Collaborators
Bayer
Investigators
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Study Director: Bayer Study Director Bayer

Additional Information:
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Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02258451     History of Changes
Other Study ID Numbers: 17096
2014-002114-23 ( EudraCT Number )
First Posted: October 7, 2014    Key Record Dates
Last Update Posted: April 4, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bayer:
Breast Cancer

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Hormones
Everolimus
Sirolimus
Exemestane
Radium Ra 223 dichloride
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists