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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

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ClinicalTrials.gov Identifier: NCT02258464
Recruitment Status : Terminated (Due to lower than expected recruitment since the start of study)
First Posted : October 7, 2014
Results First Posted : August 10, 2020
Last Update Posted : August 10, 2020
Sponsor:
Information provided by (Responsible Party):
Bayer

Tracking Information
First Submitted Date  ICMJE September 30, 2014
First Posted Date  ICMJE October 7, 2014
Results First Submitted Date  ICMJE July 1, 2020
Results First Posted Date  ICMJE August 10, 2020
Last Update Posted Date August 10, 2020
Actual Study Start Date  ICMJE March 2, 2015
Actual Primary Completion Date August 13, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 29, 2020)
Symptomatic Skeletal Event Free Survival (SSE-FS) [ Time Frame: Up to approximately 51 months ]
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
Original Primary Outcome Measures  ICMJE
 (submitted: October 6, 2014)
Symptomatic skeletal event free survival (SSE-FS) [ Time Frame: From time of randomization up to 25 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 29, 2020)
  • Overall Survival [ Time Frame: Up to approximately 51 months ]
    Time from randomization to death from any cause
  • Time to Opiate Use for Cancer Pain [ Time Frame: Up to approximately 51 months ]
    Interval from the date of randomization to the date of opiate use
  • Time to Pain Progression [ Time Frame: Up to approximately 51 months ]
    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
  • Pain Improvement Rate [ Time Frame: Up to approximately 51 months ]
    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
  • Time to Cytotoxic Chemotherapy [ Time Frame: Up to approximately 51 months ]
    Time from the date of randomization to the date of the first cytotoxic chemotherapy
  • Radiological Progression-free Survival (rPFS) [ Time Frame: Up to approximately 51 months ]
    Time from the date of randomization to the date of first radiological progression or death (if death occurs before progression)
  • Number of Participants With Treatment-emergent Adverse Events [ Time Frame: Up to approximately 7 months ]
    Any event arising or worsening after the start of study drug administration until 30 days after the last study medication intake
  • 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 ]
    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
Original Secondary Outcome Measures  ICMJE
 (submitted: October 6, 2014)
  • Overall Survival [ Time Frame: From time of randomization up to 25 months ]
  • Time to Opiate Use for Cancer Pain [ Time Frame: From time of randomization up to 25 months ]
  • Time to pain progression [ Time Frame: From time of randomization up to 25 months ]
  • Time to Cytotoxic Chemotherapy [ Time Frame: From time of randomization up to 25 months ]
  • Radiological Progression-free Survival (rPFS) [ Time Frame: From time of randomization up to 25 months ]
  • Frequency of abnormalities in laboratory examinations [ Time Frame: From time of randomization up to 25 months ]
  • Frequency of abnormalities in Adverse Events [ Time Frame: From time of randomization up to 25 months ]
  • Frequency of abnormalities in new primary malignancies [ Time Frame: From time of randomization up to 25 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
Brief Summary 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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Breast Neoplasms
Intervention  ICMJE
  • 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: Placebo (saline)
    Up to 6 cycles of saline injection
  • Other: Background hormonal therapy
    Prescribed by PI and was provided as long as patient can tolerate treatment. It must be prescribed as per local label in country participating.
Study Arms  ICMJE
  • 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
    Interventions:
    • Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
    • Other: Background hormonal therapy
  • 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
    Interventions:
    • Drug: Placebo (saline)
    • Other: Background hormonal therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 4, 2019)
99
Original Estimated Enrollment  ICMJE
 (submitted: October 6, 2014)
227
Actual Study Completion Date  ICMJE August 13, 2019
Actual Primary Completion Date August 13, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Canada,   Czechia,   Denmark,   Finland,   France,   Germany,   Hong Kong,   Ireland,   Israel,   Korea, Republic of,   Netherlands,   Norway,   Poland,   Singapore,   Spain,   Switzerland,   Taiwan,   United Kingdom,   United States
Removed Location Countries China,   Czech Republic,   Italy,   Sweden
 
Administrative Information
NCT Number  ICMJE NCT02258464
Other Study ID Numbers  ICMJE 16298
2014-002113-39 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bayer
Study Sponsor  ICMJE Bayer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bayer Study Director Bayer
PRS Account Bayer
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP