Comparing a Single-Dose vs. Twice Yearly Zoledronate in Patients With Early Stage Breast Cancer (REaCT-ZOL) (REaCT-ZOL)
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|ClinicalTrials.gov Identifier: NCT03664687|
Recruitment Status : Recruiting
First Posted : September 10, 2018
Last Update Posted : October 3, 2019
|Condition or disease||Intervention/treatment||Phase|
|Early-stage Breast Cancer||Drug: Zoledronate||Phase 4|
Breast cancer patients are at an increased risk of recurrence in bone and bone density loss (osteopenia/osteoporosis) and consequently fragility fractures due to: age, systemic therapy with aromatase inhibitors, and premature induction of menopause by chemotherapy or ovarian ablation. Bone is the most common site of breast cancer recurrence. The use of bone modifying agents, such as Zoledronate may reduce the risk of bone metastases and fragility fractures. Despite the widespread use of adjuvant Zoledronate, it is not known what the optimal number of infusions is to reduce the risk of bone metastases and the risk of fragility fractures. Indeed, the recent CCO and ASCO Practice Guideline, 'Bottom line recommendations' specifically states, "More research is recommended comparing different bone-modifying agents, doses, dosing intervals, and durations." In the metastatic setting, for nearly 2 decades biphosphonates (i.e. Zoledronate) have been given to patients every 3-4 weeks. This dosing interval was selected based on convenience of co-administration with standard anti-cancer agents and not on the long biological effect of these agents on osteoclasts, the cells responsible for excess bone breakdown. Furthermore, in the bone density preservation setting, despite the usual administration of Zoledronate once a year a single dose of Zoledronate was associated with a sustained increase in bone mineral density 5 years later. A recent systematic review in the adjuvant setting, showed that BTA at any particular dose or route of administration showed superiority over the other. In other words, the lowest dose appears to be just as good as the highest dose. This study will compare the single dose of Zoledronate to Zoledronate given every 6 months for 3 years. The primary outcome for this study will be feasibility of conducting this trial. The secondary outcome will assess bone-metastasis risk, fragility rates, quality of life, and cost-effectiveness.
In this study it is hypothesized that a single dose of Zoledronate will be non-inferior to every 6 months in terms of bone-metastasis free survival, time to first bone metastasis and fragility fractures. It is also hypothesized that a single dose of Zoledronate will have less toxicities associated with Zoledronate compared to every 6 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||200 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomised, Multicentre, Pragmatic Trial Comparing a Single-Dose vs. Twice Yearly Zoledronate in Patients With Early Stage Breast Cancer (REaCT-ZOL)|
|Actual Study Start Date :||October 31, 2018|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||December 2023|
Active Comparator: Zoledronate one dose (4 mg)
One 4 mg dose of Zoledronate
Administered intravenously (IV)
Other Name: Zoledronic acid
Active Comparator: Zoledronate 4 mg every 6 months x 3 years
One 4 mg dose of Zoledronate given every 6 months for 3 years
Administered intravenously (IV)
Other Name: Zoledronic acid
- Multiple Site Activation [ Time Frame: 12 months ]Evaluating the feasibility of multiple site activation. Measured by the number of sites activated, as well as how long it takes to get the sites activated once the first site becomes active for accrual.
- Time to Activate Six Sites [ Time Frame: 12 months ]Evaluating the amount of time it takes to get six sites activated for participant accrual.
- Medical Oncologist Active Participation [ Time Frame: Through to end of accrual, average 2 years ]Evaluating the number of medical oncologists at each study site who actively participate in the trial. Active participation includes approaching eligible patients for the study, as well as following up with patients who are taking part in the study.
- Patient Enrollment [ Time Frame: 9 months ]Evaluating the number of patients enrolled across all of the active sites within 9 months of the sixth site being activated. Number of patients enrolled across all of the active sites.
- Bone-Metastasis-Free Survival [ Time Frame: Through to end of study, average of 3 years ]Evaluate bone-metastasis-free Survival (Bone-DFS) defined as the time to first occurrence of bone metastasis (symptomatic or asymptomatic) or death from any cause.
- Time to first bone metastasis [ Time Frame: Through to end of study, average of 3 years ]Evaluate the time to first bone metastasis (symptomatic or asymptomatic, excluding deaths). The time-to-disease will start from the randomization data and ends at occurrence of the event.
- Fragility fractures rates [ Time Frame: Through to end of study, average of 3 years ]Evaluate fragility fracture rates. Fragility fractures rates; defined as fractures which result from a fall from a standing height or less, or that present in the absence of trauma (most common fragility fractures occur at the hip, wrist, spine, humerus or pelvis).
- Direct Estimation of Health Utility Values [ Time Frame: Through to end of study, average of 3 years ]To evaluate patient quality of life using the EQ-5D-5L questionnaire, undertaken at the first Zoledronate treatment and either every year (Arm A) or every 6 months (Arm B) for 3 years. The EuroQol 5 Dimension 5 Level (EQ-5D-5L) questionnaire consists of two sections; the descriptive system and the visual analogue scale. The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and has 5 levels associated with it (no problems, slight problems, moderate problems, severe problems and extreme problems). The scale range of 1-5 is used for the 5 dimensions where 1 is the best outcome and 5 is the worst outcome. The Visual Analogue scale records the respondent's self-rated health on a vertical, visual scale with endpoints labelled 'the best health you can imagine' at the top and 'the worst health you can imagine' at the bottom. This ranges 0-100 with 0 being the worst outcome and 100 being the best outcome.
- Incremental Cost-Effectiveness Ratio [ Time Frame: Through to study completion, an average of 3 years ]A statistic used in cost-effectiveness analysis to summarise the cost-effectiveness of a health care intervention. It is defined by the difference in cost between two possible interventions, divided by the difference in their effect.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03664687
|Contact: Lisa Vandermeer||613-737-7700 ext email@example.com|
|Contact: Carol Stober||613-737-7700 ext firstname.lastname@example.org|
|Ottawa Hospital Research Institute||Recruiting|
|Ottawa, Ontario, Canada, K1H 8M2|
|Principal Investigator: Mark Clemons, MD|
|Principal Investigator:||Mark Clemons, MD||Ottawa Hospital Research Institute|