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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

Tracking Information
First Submitted Date  ICMJE September 30, 2014
First Posted Date  ICMJE October 7, 2014
Last Update Posted Date April 4, 2019
Actual Study Start Date  ICMJE June 4, 2015
Estimated Primary Completion Date July 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 25, 2016)
Symptomatic skeletal event free survival (SSE-FS). [ Time Frame: From time of randomization up to 26 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 6, 2014)
Symptomatic skeletal event free survival (SSE-FS) [ Time Frame: From time of randomization up to 34 months ]
Change History Complete list of historical versions of study NCT02258451 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 7, 2016)
  • Overall survival [ Time Frame: From time of randomization up to 26 months ]
  • Time to opiate use for cancer pain [ Time Frame: From time of randomization up to 26 months ]
  • Time to pain progression (only in subjects with baseline worst pain score (WPS) ≤8) [ Time Frame: From time of randomization up to 26 months ]
  • Time to cytotoxic chemotherapy [ Time Frame: From time of randomization up to 26 months ]
  • Radiological progression-free survival (rPFS) [ Time Frame: From time of randomization up to 26 months ]
  • Frequency of abnormalities in laboratory examinations [ Time Frame: From time of randomization up to 26 months ]
  • Pain improvement rate [ Time Frame: From time of randomization up to 26 months ]
  • To measure new primary malignancies and hematopoietic reserve for tolerability of subsequent chemotherapy [ Time Frame: From time of randomization up to 26 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 6, 2014)
  • Overall survival [ Time Frame: From time of randomization up to 34 months ]
  • Time to opiate use for cancer pain [ Time Frame: From time of randomization up to 34 months ]
  • Time to pain progression [ Time Frame: From time of randomization up to 34 months ]
  • Time to cytotoxic chemotherapy [ Time Frame: From time of randomization up to 34 months ]
  • Radiological progression-free survival (rPFS) [ Time Frame: From time of randomization up to 34 months ]
  • Frequency of abnormalities in laboratory examinations [ Time Frame: From time of randomization up to 34 months ]
  • Frequency of abnormalities in Adverse Events [ Time Frame: From time of randomization up to 34 months ]
  • Frequency of abnormalities in new primary malignancies [ Time Frame: From time of randomization up to 34 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 Treatment With Exemestane / Everolimus 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 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
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.
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
  • 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.
Study Arms  ICMJE
  • 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
    Interventions:
    • Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
    • Drug: Exemestane
    • Drug: Everolimus
  • Placebo Comparator: Placebo + exemestane/everolimus
    Up to 6 cycles of saline injection (placebo) (randomized) + All patients will receive exemestane and everolimus
    Interventions:
    • Drug: Placebo (saline)
    • Drug: Exemestane
    • Drug: Everolimus
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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 4, 2018)
283
Original Estimated Enrollment  ICMJE
 (submitted: October 6, 2014)
310
Estimated Study Completion Date  ICMJE August 30, 2019
Estimated Primary Completion Date July 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
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,   Belgium,   China,   Czechia,   France,   Germany,   Hong Kong,   Israel,   Italy,   Japan,   Korea, Republic of,   Norway,   Poland,   Singapore,   Spain,   Switzerland,   Taiwan,   United Kingdom,   United States
Removed Location Countries Canada,   Czech Republic,   Netherlands
 
Administrative Information
NCT Number  ICMJE NCT02258451
Other Study ID Numbers  ICMJE 17096
2014-002114-23 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
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 April 2019

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