Study of Radium-223 Dichloride in Combination With Exemestane and Everolimus Versus Placebo in Combination With Exemestane and Everolimus in Subjects With Bone Predominant HER2 Negative Hormone Receptor Positive Metastatic Breast Cancer
Condition: Breast Neoplasms
MeSH terms: Breast Neoplasms
Intervention: Radium-223 dichloride (Xofigo, BAY88-8223); Placebo (saline); Exemestane; Everolimus
Intervention description: Up to 6 cycles of radium-223 dichloride 50kBq/kg body (55 kBq/kg after implementation of NIST update); Up to 6 cycles of saline injection; One 25 mg tablet once daily after a meal.; The recommended dose of everolimus administered in the study is 10 mg once daily with or without food.
Starting dose, dose modifications, and administration of exemestane and everolimus must be in compliance with the local labels in each of the participating countries and/or in line with local standard of practice.
Intervention MeSH terms: Everolimus; Exemestane; 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: 283.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast Cancer

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

      After implementation of CSP Amendment 10, only a limited number of subjects will remain in
      this study, in order to reduce the burden to study subjects, collection of data will be
      reduced and will focus mainly on acute safety, SSE, and OS. Once subjects are rolled over,
      the long-term safety will be collected and assessed entirely in the separate extended safety
      follow-up study.
    

Eligibility criteria:

        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.