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
Condition: Breast Neoplasms
MeSH terms: Breast Neoplasms
Intervention: Radium-223 dichloride (Xofigo, BAY88-8223); Placebo (saline); Background hormonal therapy
Intervention description: 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); 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.
Intervention MeSH terms: Radium Ra 223 dichloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 99.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast Cancer

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
    

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.