ABCSG 18 ZA Study details

A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Phase 3 Study to Determine the Treatment Effect of Denosumab in Subjects With Non-Metastatic Breast Cancer Receiving Aromatase Inhibitor Therapy/ Zoledronic Acid (ZA) Substudy

ABCSG 18 ZA was developed as an additional protocol to assess the effects of a single intravenous ZA administration on bone density, fracture incidence, and bone turnover markers (CTX and osteocalcin) in a subset of ABCSG 18 patients after discontinuation of denosumab.

Treatment arms:

single dose of Zoledronic Acid 5 mg IV (Therapy Arm)/ management according to current Standard of Care (Control Arm)

Exploratory objective:

To evaluate the impact of a single intravenous (IV)  ZA administration on bone mineral density (BMD), fracture incidence (clinical and morphometric), and bone turnover markers (C-terminal telopeptide [CTX] and Osteocalcin) in ZA substudy.

Exploratory Endpoints

  • Percent change in lumbar spine, total hip and femoral neck BMD from baseline to months 6, 12, and 18.
  • Percent change in bone turnover marker values (CTX and Osteocalcin) from baseline to months 6, 12, and 18.
  • Fracture incidence (clinical and morphometric) at baseline and then at months 6, 12, and 18 after day 1.

Inclusion Criteria for ZA Substudy

  • Obtain signed and dated written informed consent prior to performing any study-specific procedure
  • Subjects that received OLP denosumab and completed OLP treatment
  • Last OLP denosumab administration no longer than 9 months ago

Exclusion Criteria for ZA Substudy

  • Current or prior ZA administration
  • Subjects who ended treatment with investigational product (IP) prematurely in the double-blind phase and OL phase
  • Known sensitivity or intolerance to any of the products to be administered during the study (eg, ZA, calcium or vitamin D)
  • Known history of any of the following conditions either by subject self report or chart review
    • Paget’s disease (bone), Cushing’s disease, hyperprolactinemia or other active metabolic bone disease
    • Known history of hypocalcemia
    • Major surgery, or significant traumatic injury occurring within 4 weeks prior to randomization
    • Parathyroid glands in neck surgically removed
    • Any sections of intestine removed
    • Known human immunodeficiency virus infection
    • Active infection with hepatitis B or hepatitis C virus
  • Known liver or renal disease as determined by the investigator and indicated by the following criteria:
    • Aspartate aminotransferase ≥ 2.5 x ULN
    • Alanine transaminase ≥ 2.5 x ULN
    • Serum creatinine ≥ 2 x ULN
    • Creatine clearance < 35ml/min
  • Subjects that are pregnant or breastfeeding
    • All subjects with reproductive potential must have a negative pregnancy test within 7 days before randomization
  • Subjects who are osteoporotic in baseline BMD