The ODYSSEY TRIAL Phase IV Trial Evaluating the Palliative Benefit of Pamidronate or Zoledronic Acid in Breast Cancer

This study will be a prospective, randomized, double-blind, placebo controlled, Phase IV study of pamidronate vs. zoledronic acid in women with breast cancer and bone metastases. Patients who are at high-risk of subsequent SREs will be screened for entry into this study. High-risk will be defined as fulfilling one or more of the following criteria: elevated sCTX (>400ng/L) and/or bone pain and/or a prior SRE and/or progression of bone disease (by imaging) despite at least 3 months of pamidronate therapy. Patients who meet the eligibility criteria, will be randomized to receive 3 cycles of intravenous zoledronic acid (4mg intravenously over 15 minutes) or to continue their standard dose of pamidronate. Both treatments will be given at 4 week intervals. Patients will be stratified according to whether or not they have had a SRE prior to study entry, progressive bone disease or bone pain. In order for the study to be double-blind, patients will receive two infusions simultaneously, at each study visit, one of the active drug and another of the placebo. After completing 3 cycles of study treatment, patients will resume their monthly intravenous pamidronate infusions as per current standard of care.

Inclusion criteria

• Metastatic breast cancer to the bone with radiologically confirmed bone metastases
• High-risk of subsequent SRE as reflected through either: elevated serum CTX (> 400ng/L) and/or bone pain (using BPI) and/or prior SRE while on bisphosphonate therapy and/or progressive bone metastasis (by imaging)
• On pamidronate therapy for at least 3 months
• ECOG ≤ 2 and life expectancy > 3 months
• Serum creatinine ≤ 2.0 × ULN (zoledronic acid or pamidronate to be renal dosed as per institution standard)
• No changes in systemic treatment in the 4 weeks prior to study entry or anticipated changes in the 4 weeks after entering the study. Markers of bone formation can be affected by a change in systemic therapies
• Ability to take calcium and Vitamin D as per Health Canada recommended daily doses for the duration of the study
• Ability to provide informed consent and complete study evaluations.

Exclusion criteria

• Patients with acute symptomatic pathological fractures or acute spinal cord compression until such time as the appropriate management (surgery and/or radiotherapy) has been completed
• Acute hypercalcemia (>3.5 mmol/L)
• Hypersensitivity to any bisphosphonate
• Patients with rapidly progressive non-bone metastases for whom delaying a change in systemic anti-cancer treatment for the 1 month biochemical marker evaluation period could have a detrimental impact on patient outcome.
• Renal dysfunction (≥ 2x creatinine of the upper limit of normal )
• Pregnancy or lactation
• Patients with dental abscesses or patients potentially requiring tooth extraction while on study