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

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Study of Radium-223 Dichloride Versus <span class="go-doc-concept go-doc-intervention">Placebo</span> and Treatment With <span class="go-doc-concept go-doc-intervention">Exemestane</span> / <span class="go-doc-concept go-doc-intervention">Everolimus</span> in Subjects With Bone Predominant <span class="go-doc-concept go-doc-biomarker">HER2</span> (Human Epidermal Growth Factor Receptor 2) Negative Hormone Receptor Positive Metastatic <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

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

    NCT ID: NCT02258451

    ORG ID: 17096

    NCI ID: 2014-002114-23

    Trial Conditions

    Breast Neoplasms

    Trial Interventions

    Drug Synonyms Arms
    Radium-223 dichloride (Xofigo, BAY88-8223) Radium-223 dichloride + exemestane/everolimus
    Placebo (saline) Placebo + exemestane/everolimus
    Exemestane Radium-223 dichloride + exemestane/everolimus, Placebo + exemestane/everolimus
    Everolimus Radium-223 dichloride + exemestane/everolimus, Placebo + exemestane/everolimus

    Trial 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.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Radium-223 dichloride + exemestane/everolimus Experimental Up to 6 cycles of radium-223 dichloride 50kBq/kg body weight (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 are eligible
    pre-menopausal subjects with ovarian radiation or concomitant treatment with an LH-RF
    agonist/antagonist must have a plasma/serum estradiol assay of <20 pg/mL at screening
    within 7 days prior to randomization. Negative pregnancy test is also required at
    screening. Agreement to use adequate method of contraception as recommended by their
    treating physician.

    - 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: external beam radiotherapy (EBRT) for 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.

    - Asymptomatic or mildly symptomatic breast cancer.

    - Adequate hematological, liver and kidney function

    Exclusion Criteria:

    - Subjects with any of the following cancers:

    - Inflammatory breast cancer

    - Bilateral breast cancer or a history of 2 distinct breast cancers.

    - 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.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Symptomatic skeletal event free survival (SSE-FS)

    Secondary Outcome Measures

    Overall survival

    Time to opiate use for cancer pain

    Time to pain progression

    Time to cytotoxic chemotherapy

    Radiological progression-free survival (rPFS)

    Frequency of abnormalities in laboratory examinations

    Frequency of abnormalities in Adverse Events

    Frequency of abnormalities in new primary malignancies

    Trial Keywords

    Breast Cancer