Zoledronate Dosing for Breast Cancer

(REaCT-ZOL Trial)

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the optimal frequency for administering Zoledronate (also known as Zometa or Zoledronic acid) to treat early-stage breast cancer. It compares a single dose to multiple doses over three years to determine the more effective dosing schedule. Suitable candidates for this trial are those who began specific breast cancer treatments within the last three months and are not using other bone-strengthening drugs. As a Phase 4 trial, this research aims to understand how this FDA-approved and effective treatment can benefit more patients.

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 is the safety track record for Zoledronate?

Research shows that zoledronate is usually well-tolerated by patients with breast cancer. Studies have found that adding zoledronate to treatment can lower the risk of cancer returning and improve survival rates.

Regarding safety, patients have done well with different dosing schedules of zoledronate. For example, one study on patients using zoledronate for bone issues found that varying the dose did not cause new safety problems. Most side effects were mild and manageable.

The FDA has already approved zoledronate for treating other bone-related conditions, indicating it is generally safe. However, like any treatment, some patients might experience side effects. Consulting a doctor can help patients understand their personal risks and benefits. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Zoledronate for breast cancer because it offers a unique approach to treatment. Unlike standard treatments that often focus on directly targeting cancer cells, Zoledronate works by strengthening bones and potentially preventing metastasis to bone, a common issue in breast cancer. This trial is exploring two dosing regimens: a single 4 mg dose and a repeated 4 mg dose every six months for three years. The latter approach could provide sustained benefits in bone health and cancer management over time. This innovative angle has the potential to complement existing therapies, offering a new layer of protection for patients.

What is the effectiveness track record for Zoledronate in treating breast cancer?

Research has shown that zoledronate can help breast cancer patients live longer without the disease returning. Studies indicate that using zoledronate as an additional treatment after the main one can lower the chances of cancer recurrence and reduce the risk of death. In this trial, participants will receive either a single 4 mg dose of zoledronate or a 4 mg dose every 6 months for 3 years. Some studies found that even fewer doses of zoledronate did not significantly affect survival rates, suggesting that different dosing schedules could still be beneficial. Overall, zoledronate effectively treats breast cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Mark Clemons, MD

Principal Investigator

Ottawa Hospital Research Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3210470/

Zoledronic acid in breast cancer: latest findings and ... Current data support the possibility that zoledronic acid might be most effective for improving disease-free survival in the adjuvant breast cancer setting.

2. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2781088

Prognosis of Patients With Early Breast Cancer Receiving ... The frequency of adverse events was higher with 5 years of zoledronate treatment—both all grades and grades 3 or 4 only. Meaning The results of ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959804922017919

Does the number of 6-monthly adjuvant zoledronate ... Receiving fewer than 7 zoledronate infusions had no significant effect on DFS or OS. Adjuvant bisphosphonate de-escalation in breast cancer must be further ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00375427

Safety and Efficacy of Zoledronic Acid in Patients With ... The objective of this study is to assess the clinical benefit of two different dosing schedules of zoledronic acid in patients with metastatic bone lesions ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1105195

Breast-Cancer Adjuvant Therapy with Zoledronic Acid Data suggest that the adjuvant use of bisphosphonates reduces rates of recurrence and death in patients with early-stage breast cancer.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.02647

Use of Adjuvant Bisphosphonates and Other Bone ... Two Phase III studies of adjuvant denosumab did not show a consistent reduction of breast cancer recurrence in any subset of patients with early ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0959804922017919

Does the number of 6-monthly adjuvant zoledronate ... Receiving fewer than 7 zoledronate infusions had no significant effect on DFS or OS. Adjuvant bisphosphonate de-escalation in breast cancer must be further ...