Clinical Trials /

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

NCT02258451

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

  • Breast Neoplasms

Interventions

DrugSynonymsArms
Radium-223 dichloride (Xofigo, BAY88-8223)Radium-223 dichloride + exemestane/everolimus
Placebo (saline)Placebo + exemestane/everolimus
ExemestanePlacebo + exemestane/everolimus
EverolimusPlacebo + 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

NameTypeDescriptionInterventions
Radium-223 dichloride + exemestane/everolimusExperimentalUp 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/everolimusPlacebo ComparatorUp 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

  • Breast Cancer

Last Updated

April 6, 2021