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

Bayer

Status and phase: Completed; Phase 2

Conditions: Breast Neoplasms

Treatments: Drug: Everolimus; Drug: Exemestane; Drug: Radium-223 dichloride (Xofigo, BAY88-8223); Drug: Placebo (saline)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02258451

17096

2014-002114-23 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 283 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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283 participants in 2 patient groups, including a placebo group

Radium-223 dichloride + exemestane/everolimus

Experimental group

Description:

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). Participants will also receive exemestane, 25-mg tablet once daily (after a meal), and everolimus, 10 mg once daily (with or without food), and supportive care as per the local or institutional standard of practice.

Treatment:

Drug: Exemestane

Drug: Radium-223 dichloride (Xofigo, BAY88-8223)

Drug: Everolimus

Placebo + exemestane/everolimus

Placebo Comparator group

Description:

Up to 6 cycles of saline injection (placebo) (randomized). Participants will also receive exemestane, 25-mg tablet once daily (after a meal), and everolimus, 10 mg once daily (with or without food), and supportive care as per the local or institutional standard of practice.

Treatment:

Drug: Exemestane

Drug: Everolimus

Drug: Placebo (saline)