Description:
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.
Title
- Brief Title: 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: 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
Clinical Trial IDs
- ORG STUDY ID:
17096
- SECONDARY ID:
2014-002114-23
- NCT ID:
NCT02258451
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Radium-223 dichloride (Xofigo, BAY88-8223) | | Radium-223 dichloride + exemestane/everolimus |
Placebo (saline) | | Placebo + exemestane/everolimus |
Exemestane | | Placebo + exemestane/everolimus |
Everolimus | | Placebo + exemestane/everolimus |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Radium-223 dichloride + exemestane/everolimus | Experimental | 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 | - Radium-223 dichloride (Xofigo, BAY88-8223)
- Exemestane
- Everolimus
|
Placebo + exemestane/everolimus | Placebo Comparator | Up to 6 cycles of saline injection (placebo) (randomized) + All patients will receive exemestane and everolimus | - Placebo (saline)
- Exemestane
- Everolimus
|
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Female |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Symptomatic skeletal event free survival (SSE-FS). |
Time Frame: | From time of randomization up to 61 months |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Overall survival |
Time Frame: | From time of randomization up to 61 months |
Safety Issue: | |
Description: | |
Measure: | Time to opiate use for cancer pain |
Time Frame: | From time of randomization up to 61 months |
Safety Issue: | |
Description: | |
Measure: | Time to pain progression (only in subjects with baseline worst pain score (WPS) ≤8) |
Time Frame: | From time of randomization up to 61 months |
Safety Issue: | |
Description: | |
Measure: | Time to cytotoxic chemotherapy |
Time Frame: | From time of randomization up to 61 months |
Safety Issue: | |
Description: | |
Measure: | Radiological progression-free survival (rPFS) |
Time Frame: | From time of randomization up to 61 months |
Safety Issue: | |
Description: | |
Measure: | Frequency of abnormalities in laboratory examinations |
Time Frame: | From time of randomization up to 61 months |
Safety Issue: | |
Description: | |
Measure: | Pain improvement rate |
Time Frame: | From time of randomization up to 61 months |
Safety Issue: | |
Description: | |
Measure: | To measure new primary malignancies and hematopoietic reserve for tolerability of subsequent chemotherapy |
Time Frame: | From time of randomization up to 61 months |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Bayer |
Trial Keywords
Last Updated
August 17, 2021