ER11-03: The ODYSSEY TRIAL Phase IV Trial Evaluating the Palliative Benefit of Pamidronate or Zoledronic Acid in Breast Cancer

Sponsor

Ottawa Hospital Research Institute (Other)

Overall Status

Completed

CT.gov ID

NCT01907880

Collaborator

Canadian Breast Cancer Foundation (Other)

Enrollment

Location

Arms

Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Pamidronate Drug: Zoledronic acid Drug: placebo	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

74 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Placebo-controlled, Phase IV Trial Evaluating the Palliative Benefit of Either Continuing Pamidronate or Switching to Second-line Zoledronic Acid in Breast Cancer Patients With High-risk Bone Metastases.

Study Start Date :

Aug 1, 2012

Actual Primary Completion Date :

Jan 1, 2016

Actual Study Completion Date :

Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Drug: Pamidronate 90mg IV once every 4 weeks for 3 cycles Other Names: ADP Sodium Aredia® Drug: placebo
Active Comparator: 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.	Drug: Zoledronic acid 4mg IV every 4 weeks for 3 cycles Other Names: Reclast Zometa Aclasta Drug: placebo

Arm

Intervention/Treatment

Active Comparator: 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.

Drug: Pamidronate

90mg IV once every 4 weeks for 3 cycles

Other Names:

ADP Sodium

Aredia®

Drug: placebo

Active Comparator: 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.

Drug: Zoledronic acid

4mg IV every 4 weeks for 3 cycles

Other Names:

Reclast

Zometa

Aclasta

Drug: placebo

Outcome Measures

Primary Outcome Measures

sCTX values [baseline, 1 week post treatment, week 4, week 8, week 12]
To compare the proportion of high-risk metastatic breast cancer patients with bone metastases that will achieve a decrease in sCTX (surrogate for decrease risk of SREs) in the zoledronic and pamidronate treatment arms.

Secondary Outcome Measures

Palliative response [baseline, week 1, week 4, week 8, week 12.]
To determine the proportion of high-risk metastatic breast cancer patients that will achieve a significant improvement in palliative response (18) (defined as a two unit drop in their worst pain score, based on a brief pain inventory questionnaire for two consecutive measurements at least one month apart) in the zoledronic and pamidronate treatment arms.

Other Outcome Measures

predictor of pain benefit [week 1 and week 12]
To assess whether a drop in sCTX one week post infusion of zoledronic acid is a predictor of pain benefit at week 12. We will test the strength of the association in sCTX drop (any drop from baseline level) at week 1 and palliative response when measured at week 12, using the validated BPI and FACT-BP questionnaires

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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