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

NCT ID: NCT01907880

Last Updated: 2017-07-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2016-01-31

Brief Summary

Metastatic breast cancer patients with bone involvement who are at high-risk of subsequent skeletal related event (SRE), defined as radiotherapy or surgery to the bone, pathological fracture, spinal cord compression, or hypercalcemia (as reflected through: elevated sCTX or bone pain or a prior SRE despite receiving standard bisphosphonate therapy) should experience a decrease in the surrogate marker, sCTX, at week 12 if switched to zoledronic acid compared with those patients who continue on intravenous pamidronate (i.e. current standard of care). The investigators propose that a drop in sCTX will correlate with improved pain, quality of life and a reduced incidence of further SREs.

Detailed Description

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Pamidronate and placebo

Patients will receive two infusions simultaneously, at each study visit, one of Pamidronate 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.

Group Type: ACTIVE_COMPARATOR

Pamidronate

Intervention Type: DRUG

90mg IV once every 4 weeks for 3 cycles

placebo

Intervention Type: DRUG

Zoledronic acid and placebo

Patients will receive two infusions simultaneously, at each study visit, one of Zoledronic acid 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.

Group Type: ACTIVE_COMPARATOR

Zoledronic acid

Intervention Type: DRUG

4mg IV every 4 weeks for 3 cycles

placebo

Intervention Type: DRUG

Interventions

Pamidronate

90mg IV once every 4 weeks for 3 cycles

Intervention Type: DRUG

Zoledronic acid

4mg IV every 4 weeks for 3 cycles

Intervention Type: DRUG

placebo

Intervention Type: DRUG

Other Intervention Names

ADP Sodium; Aredia®; Reclast; Zometa; Aclasta

Eligibility Criteria

Inclusion Criteria

1. Metastatic breast cancer to the bone with radiologically confirmed bone metastases

2. 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)

3. On pamidronate therapy for at least 3 months

4. ECOG ≤ 2 and life expectancy > 3 months

5. Serum creatinine ≤ 2.0 × ULN (zoledronic acid or pamidronate to be renal dosed as per institution standard)

6. 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

7. Ability to take calcium and Vitamin D as per Health Canada recommended daily doses for the duration of the study

8. Ability to provide informed consent and complete study evaluations.

Exclusion Criteria

1. 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

2. Acute hypercalcemia (>3.5 mmol/L)

3. Hypersensitivity to any bisphosphonate

4. 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.

5. Renal dysfunction (≥ 2x creatinine of the upper limit of normal )

6. Pregnancy or lactation

7. Patients with dental abscesses or patients potentially requiring tooth extraction while on study

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Canadian Breast Cancer Foundation

OTHER

Sponsor Role: collaborator

Ottawa Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Clemons, Dr.

Role: PRINCIPAL_INVESTIGATOR

The Ottawa Hospital

Locations

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Countries

Canada

Other Identifiers

2011349-01H

Identifier Type: -

Identifier Source: org_study_id