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

ID: NCT02258464
Status: Active, not recruiting
Phase: Phase 2
Start Date: February 17, 2015
First Submitted: September 30, 2014
Last Updated: February 21, 2018
Results: N/A
Organization: Bayer
Sponsors & Collaborators: Bayer
Location: Austria, Canada, Czechia, Finland, France, Germany, Hong Kong, Ireland, Israel, Korea, Republic of, Netherlands, Norway, Poland, Singapore, Spain, Taiwan, United Kingdom, United States
Conditions: Breast Neoplasms
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Study Description

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 negative (HER2 negative) hormone receptor positive breast cancer with bone metastases treated with hormonal treatment background therapy.

Detailed Description

Condition or disease Intervention/treatment Phase

Breast Neoplasms

Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
Other Names
Drug: Placebo (saline)
Other Names
Other: Background hormonal therapy
Other Names
Phase 2

Tracking Information

First Submitted DateSeptember 30, 2014
Last Update Posted DateFebruary 21, 2018
Actual Start DateFebruary 17, 2015
Anticipated Completion DateAugust 15, 2018
Actual Primary Completion DateAugust 15, 2018
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Symptomatic skeletal event free survival (SSE-FS). [Time Frame: From time of randomization up to 25 months]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • 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 (only in subjects with baseline worst pain score ≤8) [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]

  • Pain Improvement Rate [Time Frame: From time of randomization up to 25 months]

  • To measure new primary malignancies and hematopoietic reserve for tolerability of subsequent chemotherapy [Time Frame: From time of randomization up to 25 months]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleStudy 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 TitleA 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 is 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

Study TypeInterventional
Study PhasePhase 2
Estimated Enrollment
100
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Quadruple
Primary Purpose
Treatment
Conditions
Breast Neoplasms
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
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)

Other Names
Drug: Placebo (saline)

Up to 6 cycles of saline injection

Other Names
Other: Background hormonal therapy

Prescribed by PI and is provided as long as patient can tolerate treatment. It must be prescribed as per local label in country participating.

Other Names
Study Groups/Cohorts
Radium-223 dichloride + hormonal therapy
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) + Hormonal therapy background treatment to be prescribed by Principal Investigator

Placebo + hormonal therapy
Up to 6 cycles of saline injection (placebo) (Randomized) + Hormonal therapy background treatment to be prescribed by Principal Investigator

Study Arms
Placebo Comparator Placebo + hormonal therapy
Up to 6 cycles of saline injection (placebo) (Randomized) + Hormonal therapy background treatment to be prescribed by Principal Investigator
Drug : Placebo (saline)
Up to 6 cycles of saline injection

Placebo Comparator Placebo + hormonal therapy
Up to 6 cycles of saline injection (placebo) (Randomized) + Hormonal therapy background treatment to be prescribed by Principal Investigator
Other : Background hormonal therapy
Prescribed by PI and is provided as long as patient can tolerate treatment. It must be prescribed as per local label in country participating.

Experimental Radium-223 dichloride + hormonal therapy
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) + Hormonal therapy background treatment to be prescribed by Principal Investigator
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)

Experimental Radium-223 dichloride + hormonal therapy
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) + Hormonal therapy background treatment to be prescribed by Principal Investigator
Other : Background hormonal therapy
Prescribed by PI and is provided as long as patient can tolerate treatment. It must be prescribed as per local label in country participating.

Arm Intervention/Treatment
Placebo Comparator Placebo + hormonal therapy
Up to 6 cycles of saline injection (placebo) (Randomized) + Hormonal therapy background treatment to be prescribed by Principal Investigator
Drug : Placebo (saline)
Placebo Comparator Placebo + hormonal therapy
Up to 6 cycles of saline injection (placebo) (Randomized) + Hormonal therapy background treatment to be prescribed by Principal Investigator
Other : Background hormonal therapy
Experimental Radium-223 dichloride + hormonal therapy
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) + Hormonal therapy background treatment to be prescribed by Principal Investigator
Drug : Radium-223 dichloride (Xofigo, BAY88-8223)
Experimental Radium-223 dichloride + hormonal therapy
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) + Hormonal therapy background treatment to be prescribed by Principal Investigator
Other : Background hormonal therapy

Recruitment Information

Recruitment Status:Active, not recruiting
Enrollment100
Completion DateAugust 15, 2018
Eligibility Criteria: 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.
GenderFemale
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Not Available
Listed Location Countries
Austria
Canada
Czechia
Finland
France
Germany
Hong Kong
Ireland
Israel
Korea, Republic of
Netherlands
Norway
Poland
Singapore
Spain
Taiwan
United Kingdom
United States
China
Czech Republic
Denmark
Italy
Sweden
Switzerland

Administrative Information

NCT Number:NCT02258464
Other Study ID Numbers
16298
2014-002113-39
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Bayer
Collaborators
Not Available
Investigators
Study Director
Bayer Study Director
Bayer