Zoledronate Dosing for Breast Cancer

(REaCT-ZOL Trial)

Recruiting at 5 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Ottawa Hospital Research Institute

Must not be taking: Biphosphonates, Denosumab

Disqualifiers: Metastatic disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 3 years

211 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

If you are taking any medications for osteoporosis, like intravenous or oral bisphosphonates or subcutaneous denosumab, you will need to stop them before starting the trial.

What data supports the effectiveness of the drug Zoledronate for breast cancer?

Research shows that Zoledronate, when added to chemotherapy, can improve survival in postmenopausal breast cancer patients and reduce complications from bone metastases. It also helps prevent bone loss and may reduce the risk of cancer returning. ^{1 2 3 4 5}

Is zoledronic acid safe for use in humans?

Zoledronic acid, also known as Zometa, has been tested in various clinical trials and is generally well tolerated in humans. Some common side effects include reactions similar to flu symptoms, and there is a risk of kidney problems with high doses. Overall, it has been used safely in patients with bone diseases and cancer-related bone issues. ^{6 7 8 9 10}

How is the drug Zoledronate unique in treating breast cancer?

Zoledronate is unique because it is a highly potent bisphosphonate that not only helps manage bone complications in breast cancer patients with bone metastases but also shows potential in preventing bone loss and reducing disease recurrence. It can be administered less frequently than other treatments, such as pamidronate, and may have additional antitumor effects. ^{3 4 5 9 11}

What is the purpose of this trial?

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

Research Team

Mark Clemons, MD

Principal Investigator

Ottawa Hospital Research Institute

Eligibility Criteria

This trial is for adults over 18 with early stage breast cancer, starting treatment or within 3 months post-chemotherapy. Participants need functioning kidneys, normal calcium levels, and a life expectancy over a year. They must not be pregnant or at risk of pregnancy without using two effective contraceptives unless surgically sterile.

Inclusion Criteria

My kidney function is good and my calcium levels are normal.

I started or will start zoledronate close to my hormone or chemotherapy treatment for early breast cancer.

I am not currently taking any medications for osteoporosis.

Exclusion Criteria

My cancer has spread to other parts of my body.

I have had osteonecrosis of the jaw.

Any mental, family, social, or location-related issue that might make it hard for you to follow the trial's plan.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a single 4 mg dose of Zoledronate or a 4 mg dose every 6 months for 3 years

3 years

Every 6 months (in-person)

Follow-up

Participants are monitored for bone-metastasis-free survival, fragility fracture rates, and quality of life

3 years

Treatment Details

Interventions

• Zoledronate

Trial Overview The REaCT-ZOL study is testing the effectiveness of Zoledronate given as a single dose versus every six months for three years in patients with early stage breast cancer to see which dosing schedule works better.

Participant Groups

Group I: Zoledronate one dose (4 mg) Active Control 1 Intervention

One 4 mg dose of Zoledronate

Group II: Zoledronate 4 mg every 6 months x 3 years Active Control 1 Intervention

One 4 mg dose of Zoledronate given every 6 months for 3 years

Zoledronate is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Zometa for:

• Bone metastases from solid tumours
• Multiple myeloma
• Paget's disease of bone
• Osteoporosis in postmenopausal women

Approved in United States as Zometa for:

• Multiple myeloma and bone metastases from solid tumors
• Paget's disease of bone
• Osteoporosis in postmenopausal women

Approved in Canada as Zometa for:

• Multiple myeloma and bone metastases from solid tumors
• Paget's disease of bone
• Osteoporosis in postmenopausal women

Approved in Japan as Zometa for:

• Multiple myeloma and bone metastases from solid tumors
• Paget's disease of bone
• Osteoporosis in postmenopausal women

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

Findings from Research

In a study of 9,874 lung cancer patients with bone metastases, treatment with Zometa (zoledronic acid) significantly reduced fracture risk by 40% compared to those not receiving intravenous bisphosphonates, with even short-term use (31-90 days) showing a 47% reduction in fracture risk.

Patients treated with Zometa also experienced lower mortality rates, with a mean of 38.6 deaths per 100 person-years compared to 46.8 for those not treated with Zometa, indicating that longer treatment duration leads to better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective evaluation of the clinical benefit of long-term continuous use of zoledronic acid in patients with lung cancer and bone metastases. Henk, HJ., Kaura, S., Teitelbaum, A.[2019]

In a study of 120 women with locally advanced breast cancer, adding zoledronic acid (ZOL) to neoadjuvant chemotherapy did not improve overall clinical outcomes, such as time to recurrence or survival rates, compared to chemotherapy alone.

However, younger ER+/HER2- patients treated with ZOL experienced significantly worse time to recurrence and trends towards poorer survival outcomes, indicating that ZOL may not be safe for this specific group and highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcome of (neo)adjuvant zoledronic acid therapy in locally advanced breast cancer. Jallouk, AP., Paravastu, S., Weilbaecher, K., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Effects of neoadjuvant chemotherapy with or without zoledronic acid on pathological response: A meta-analysis of randomised trials. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Retrospective evaluation of the clinical benefit of long-term continuous use of zoledronic acid in patients with lung cancer and bone metastases. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Zoledronic acid: a review of its use in breast cancer. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Long-term outcome of (neo)adjuvant zoledronic acid therapy in locally advanced breast cancer. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Dosing of zoledronic acid throughout the treatment continuum in breast cancer. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Zoledronic acid (Zometa) use in bone disease. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Retrospective database analysis of the effect of zoledronic acid on skeletal-related events and mortality in women with breast cancer and bone metastasis in a managed care plan. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of 12-weekly versus 4-weekly zoledronic acid for prolonged treatment of patients with bone metastases from breast cancer (ZOOM): a phase 3, open-label, randomised, non-inferiority trial. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Zoledronic acid in cancer patients with bone metastases: results of Phase I and II trials. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

The role of zoledronic acid in cancer: clinical studies in the treatment and prevention of bone metastases. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion. [2022]