- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02258464
Study of Radium-223 Dichloride Versus Placebo and Hormonal Treatment as Background Therapy in Subjects With Bone Predominant HER2 (Human Epidermal Growth Factor Receptor 2) Negative Hormone Receptor Positive Metastatic Breast Cancer
July 29, 2020 updated by: Bayer
A Phase II Randomized, Double-blind, Placebo-controlled Trial of Radium-223 Dichloride Versus Placebo When Administered to Metastatic HER2 Negative Hormone Receptor Positive Breast Cancer Subjects With Bone Metastases Treated With Hormonal Treatment Background Therapy
The objective of this study was to assess efficacy and safety of radium-223 dichloride in subjects with human epidermal growth factor receptor 2 negative (HER2 negative) hormone receptor positive breast cancer with bone metastases treated with hormonal treatment background therapy
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
99
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Innsbruck, Austria, 6020
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Oberösterreich
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Linz, Oberösterreich, Austria, 4020
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Manitoba
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Winnipeg, Manitoba, Canada, R3E 0V9
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Ontario
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London, Ontario, Canada, N6A 4L6
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Newmarket, Ontario, Canada, L3Y 2P9
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Toronto, Ontario, Canada, M5G 2M9
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Ostrava, Czechia, 708 52
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Praha 2, Czechia, 12808
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Copenhagen, Denmark, 2100
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Herlev, Denmark, 2730
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Helsinki, Finland, 00290
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Tampere, Finland, FIN-33520
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Angers Cedex, France, 49055
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Saint Cloud, France, 92210
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Baden-Württemberg
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Tübingen, Baden-Württemberg, Germany, 72076
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Nordrhein-Westfalen
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Bonn, Nordrhein-Westfalen, Germany, 53105
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Essen, Nordrhein-Westfalen, Germany, 45147
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Kowloon, Hong Kong
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Cork, Ireland
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Dublin, Ireland, 7
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Afula, Israel, 1834111
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Haifa, Israel, 3109601
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Jerusalem, Israel, 9112001
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Jerusalem, Israel, 9103102
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Kfar Saba, Israel, 4428164
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Ramat Gan, Israel, 5262000
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Tel Aviv, Israel, 64239
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Zerifin, Israel, 7030000
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Busan, Korea, Republic of, 49241
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Daegu, Korea, Republic of, 42601
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Incheon, Korea, Republic of
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Seoul, Korea, Republic of, 03080
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Seoul, Korea, Republic of, 120-752
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Seoul, Korea, Republic of, 05505
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Nieuwegein, Netherlands, 3435 CM
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Zwolle, Netherlands, 8025 AB
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Oslo, Norway, 0424
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Bialystok, Poland, 15-027
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Gdynia, Poland, 81-519
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Warszawa, Poland, 02-781
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Singapore, Singapore, 119074
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A Coruña, Spain, 15009
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Barcelona, Spain, 08036
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Barcelona, Spain, 08025
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Madrid, Spain, 28040
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Madrid, Spain, 28041
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Madrid, Spain, 28033
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Málaga, Spain, 29010
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Sevilla, Spain, 41071
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Zaragoza, Spain, 50009
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Barcelona
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L'Hospitalet de Llobregat, Barcelona, Spain, 08907
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Aargau
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Aarau, Aargau, Switzerland, 5001
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Taipei, Taiwan, 11217
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Cottingham, United Kingdom, HU16 5JQ
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Merseyside, United Kingdom, CH63 4JY
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Sheffield, United Kingdom, S10 2SJ
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Devon
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Plymouth, Devon, United Kingdom, PL6 8DH
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Middlesex
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Northwood, Middlesex, United Kingdom, HA6 2RN
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Nottinghamshire
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Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
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Somerset
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Taunton, Somerset, United Kingdom, TA1 5DA
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California
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Bakersfield, California, United States, 93309
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La Jolla, California, United States, 92093
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Colorado
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Aurora, Colorado, United States, 80045
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Connecticut
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New Haven, Connecticut, United States, 06520
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Iowa
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Cedar Rapids, Iowa, United States, 52403
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Maryland
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Annapolis, Maryland, United States, 21401
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Michigan
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Ann Arbor, Michigan, United States, 48109
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Pontiac, Michigan, United States, 48341
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Missouri
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Saint Louis, Missouri, United States, 63110
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15213-3180
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Texas
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Houston, Texas, United States, 77230
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
Inclusion Criteria:
- Documentation of histological or cytological confirmation of estrogen receptor positive (ER+) and HER2 negative adenocarcinoma of the breast must be available.
- Women (≥18 years of age) with metastatic breast cancer not amenable to curative treatment by surgery or radiotherapy.
- Documentation of menopausal status: post menopausal or premenopausal subjects are eligible.
- Subjects with bone dominant disease with at least 2 skeletal metastases identified at baseline by bone scintigraphy and confirmed by CT/magnetic resonance imaging (MRI). Presence of metastases in soft tissue (skin, subcutaneous, muscle, fat, lymph nodes)and/or visceral metastases is allowed.
- Measurable or non-measurable disease (but radiologically evaluable) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
- Subjects must have received at least one line of hormonal therapy in the metastatic setting
- Subjects who are eligible for further standard of care endocrine treatment.
- Subjects enrolled in the current study must start treatment with the single hormone agent either within 15 days prior to randomization or after randomization (before or simultaneously to the first injection of Ra-223/placebo).
- Subjects must have experienced no more than two skeletal-related events (SREs) prior to study entry defined as: Need for external beam radiotherapy (EBRT) tor bone, 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 bisphosphonate and denosumab. and are required to have been on such therapy for at least 1 month before start of study treatment.
- Adequate hematological, liver and kidney function.
Exclusion Criteria:
- Subjects with Inflammatory breast cancer.
- 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.
- 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.
- Known presence of osteonecrosis of jaw.
- Patients with immediately life-threatening visceral disease, for whom chemotherapy is the preferred treatment option.
- Lymphangitic carcinomatosis.
- Patients with ascites requiring paracentesis within 2 weeks prior to study entry (signature of informed consent) and during the screening period.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Radium 223 dichloride
Participants treated with a single hormonal agent as background therapy received 50 kBq/kg body weight (55 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) of Radium 223 dichloride intravenously for a maximum of 6 cycles at intervals of 4 weeks
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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)
Prescribed by PI and was provided as long as patient can tolerate treatment.
It must be prescribed as per local label in country participating.
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Placebo Comparator: Placebo
Participants treated with a single hormonal agent as background therapy received isotonic saline (0.9% sodium chloride solution for injection) intravenously for a maximum of 6 cycles at intervals of 4 weeks
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Up to 6 cycles of saline injection
Prescribed by PI and was provided as long as patient can tolerate treatment.
It must be prescribed as per local label in country participating.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Symptomatic Skeletal Event Free Survival (SSE-FS)
Time Frame: Up to approximately 51 months
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Time from date of randomization to occurrence of one of the following, whichever happened earlier: 1) an on study SSE, which was defined as 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; or 2) death from any cause
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Up to approximately 51 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Overall Survival
Time Frame: Up to approximately 51 months
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Time from randomization to death from any cause
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Up to approximately 51 months
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Time to Opiate Use for Cancer Pain
Time Frame: Up to approximately 51 months
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Interval from the date of randomization to the date of opiate use
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Up to approximately 51 months
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Time to Pain Progression
Time Frame: Up to approximately 51 months
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Time from randomization to the first date a participants (only in participants with baseline WPS ≤8) experiences pain progression based on worst pain score (WPS) ranging from 0 to 10 and analgesic use.
Pain progression is defined as an increase of 2 or more points in the "Worst pain in 24 hours" score from baseline observed at 2 consecutive evaluations ≥4 weeks apart or an increase in pain management (IPM) with respect to baseline, whichever occurs first
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Up to approximately 51 months
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Pain Improvement Rate
Time Frame: Up to approximately 51 months
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The percentage of participants (baseline WPS>=2) with confirmed pain improvement at any time point.
Confirmed pain improvement is defined as a 2 point decrease in worst pain score (WPS) from baseline over 2 consecutive assessment periods conducted at least 4 weeks apart
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Up to approximately 51 months
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Time to Cytotoxic Chemotherapy
Time Frame: Up to approximately 51 months
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Time from the date of randomization to the date of the first cytotoxic chemotherapy
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Up to approximately 51 months
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Radiological Progression-free Survival (rPFS)
Time Frame: Up to approximately 51 months
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Time from the date of randomization to the date of first radiological progression or death (if death occurs before progression)
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Up to approximately 51 months
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Number of Participants With Treatment-emergent Adverse Events
Time Frame: Up to approximately 7 months
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Any event arising or worsening after the start of study drug administration until 30 days after the last study medication intake
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Up to approximately 7 months
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Number of Participants With Post-treatment Adverse Events Including Additional Malignancies and Chemotherapy Related Adverse Events
Time Frame: From 30 days after the last dose of study treatment until the end of study, assessed up to approximately 44 months
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AEs related to the study drug, all occurrences of additional malignancies, febrile neutropenia and hemorrhage in subjects receiving chemotherapy, bone fractures and bone associated events (regardless of severity and relationship to study drug), and some symptoms needed for the characterization of an symptomatic skeletal event
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From 30 days after the last dose of study treatment until the end of study, assessed up to approximately 44 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 2, 2015
Primary Completion (Actual)
August 13, 2019
Study Completion (Actual)
August 13, 2019
Study Registration Dates
First Submitted
September 30, 2014
First Submitted That Met QC Criteria
October 6, 2014
First Posted (Estimate)
October 7, 2014
Study Record Updates
Last Update Posted (Actual)
August 10, 2020
Last Update Submitted That Met QC Criteria
July 29, 2020
Last Verified
July 1, 2020
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 16298
- 2014-002113-39 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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