Study to Determine Treatment Effects of Denosumab in Patients With Breast Cancer Receiving Aromatase Inhibitor Therapy
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to determine whether denosumab compared to placebo, will reduce
      the rate of first clinical fracture in women with non-metastatic breast cancer receiving
      (non-steroidal) aromatase inhibitor therapy.
    

Detailed description: 
      Participants will remain on treatment until the required number of events (where an event is
      defined as first clinical fracture) is reached and all participants have had the opportunity
      to receive a minimum of at least 2 doses of study drug, whichever occurs later. The primary
      analysis data cut-off date (PADCD) is defined as the time at which the required number of
      events is reached and all participants have had the opportunity to receive at least 2 doses
      of study drug. When the PADCD is reached, all participants will discontinue study drug.

      Following the study PADCD, participants will be followed every 12 months starting from their
      last study visit until a maximum of 66 months after PADCD.

      After approval of Amendment 4, willing and eligible participants randomized to placebo during
      the double-blind phase may participate in an open-label phase (OLP) and receive denosumab 60
      mg Q6M for up to 36 months (maximum of 7 doses).

      After approval of Amendment 6 in 2019 a zoledronic acid (ZA) substudy was added to the
      protocol. Willing and eligible participants who participated in the OLP of the study and
      completed open-label denosumab may opt in to this ZA substudy and either receive a single
      dose of ZA (Therapy Arm), or be managed according to the current standard of care for this
      patient population (Control Arm).
    

Intervention name(s): Placebo; Denosumab; Non-steroidal aromatase inhibitor therapy; Zoledronic Acid; Standard of Care
Intervention type(s): Drug; Biological; Drug; Drug; Other
Intervention description(s): Administered as a subcutaneous injection; An approved non-steroidal aromatase inhibitor therapy (eg, anastrazole) in the adjuvant setting; 5 mg zoledronic acid administered at a constant infusion rate; Standard of care (SoC) as recommended by the treating physician, depending on individual factors such as bone density, lifestyle recommendations by the Investigator such as diet, physical activities and sun exposure, as well as local treatment standards.
Other intervention name(s): Administered as a subcutaneous injection; Prolia®; Reclast; Zometa
Intervention MeSH terms: Zoledronic Acid; Denosumab; Aromatase Inhibitors
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: confirmed adenocarcinoma; non-metastatic breast cancer; estrogen receptor positive; progesterone receptor positive; non-steroidal aromatase; aromatase inhibitor therapy; postmenopausal woman; adjuvant chemotherapy; neoadjuvant chemotherapy