Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Comparing a Single-Dose vs. Twice Yearly Zoledronate in Patients With Early Stage Breast Cancer (REaCT-ZOL) (REaCT-ZOL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03664687
Recruitment Status : Recruiting
First Posted : September 10, 2018
Last Update Posted : November 29, 2018
Sponsor:
Information provided by (Responsible Party):
Ottawa Hospital Research Institute

Brief Summary:
REaCT ZOL will compare one 4 mg dose of Zoledronate vs. one 4 mg dose of Zoledronate given every 6 months for 3 years.

Condition or disease Intervention/treatment Phase
Early-stage Breast Cancer Drug: Zoledronate Phase 4

Detailed Description:

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Active Comparator: Zoledronate one dose (4 mg)
One 4 mg dose of Zoledronate
Drug: 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
Drug: Zoledronate
Administered intravenously (IV)
Other Name: Zoledronic acid




Primary Outcome Measures :
  1. 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.

  2. Time to Activate Six Sites [ Time Frame: 12 months ]
    Evaluating the amount of time it takes to get six sites activated for participant accrual.

  3. 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.

  4. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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).

  4. 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.

  5. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Commencing zoledronate within 3 months of starting neoadjuvant or adjuvant endocrine therapy or within 3 months of completion of neoadjuvant or adjuvant chemotherapy for early stage breast cancer
  • Patients receiving any intravenous or oral biphosphonates, or subcutaneous denosumab for the treatment of osteoporosis must discontinue treatment prior to baseline evaluation
  • ECOG performance status equal or less than 2 and life expectancy of more than 12 months
  • Serum creatinine greater than 30 ml/min and corrected serum calcium equal or greater than 2 mmol/l within 4 weeks before first zoledronate infusion
  • Age equal or greater than 18 years
  • Able to provide written consent

Exclusion Criteria:

  • Metastatic disease
  • History of osteonecrosis of the jaw
  • Known hypersensitivity to trial drug or hypersensitivity to any other component of the trial drug (e.g. fructose)
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the trial protocol
  • Pregnancy or risk of pregnancy (this includes participants that are not willing to practice active contraception for the duration of the study)* *Women/men of child bearing potential must have agreed to use two effective contraceptive methods while on study. A women is considered to be of 'childbearing potential' if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods. 'effective contraception' also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as complete hysterectomy, bilateral oophorectomy or bilateral tubal ligation, or vasectomy/vasectomized partner. However, if at any point a previously celibate participant chooses to become heterosexually active during the period for use of contraceptive measures outlined in the protocol, she is responsible for beginning contraceptive measures. Examples of effective methods of contraception: Male condom plus spermicide; Cap plus spermicide; Diaphragm plus spermicide; intrauterine device (Copper T, Progesterone T; Levonorgestrel-releasing intrauterine system (i.e. Mirena); hormonal methods (implants, hormonal shot or injection, combined pill, minipill, patch).

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Lisa Vandermeer 613-737-7700 ext 73039 lvandermeer@toh.ca
Contact: Carol Stober 613-737-77226 cstober@toh.ca

Locations
Layout table for location information
Canada, Ontario
Ottawa Hospital Research Institute Recruiting
Ottawa, Ontario, Canada, K1H 8M2
Principal Investigator: Mark Clemons, MD         
Sponsors and Collaborators
Ottawa Hospital Research Institute
Investigators
Layout table for investigator information
Principal Investigator: Mark Clemons, MD Ottawa Hospital Research Institute

Layout table for additonal information
Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT03664687     History of Changes
Other Study ID Numbers: OTT 18-01
First Posted: September 10, 2018    Key Record Dates
Last Update Posted: November 29, 2018
Last Verified: November 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ottawa Hospital Research Institute:
Adjuvant Zoledronate

Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Zoledronic Acid
Bone Density Conservation Agents
Physiological Effects of Drugs