Zoledronic Acid for Chondrosarcoma

Overseen By Mohammed Milhem, MBBS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mohammed Milhem

Must not be taking: Osteoclast inhibitors

Disqualifiers: Impaired cardiac function, Uncontrolled hypertension, Renal disease, others

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

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

Compensation: Varies

Number of Visits: 10

Duration: 6 weeks

17 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this single arm open label phase 1b clinical study is to see what effect zoledronic acid has on tumors in patients with resectable any grade chondrosarcoma prior to surgery.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot use any anti-cancer therapy or radiation therapy while participating.

What evidence supports the effectiveness of the drug Zoledronic Acid for treating chondrosarcoma?

Research shows that Zoledronic Acid can slow down the development and progression of chondrosarcoma in animal models, increase overall survival, and inhibit tumor cell growth. This suggests it might be beneficial as an additional therapy alongside surgery for chondrosarcoma. ^{1 2 3 4 5}

Is Zoledronic Acid safe for humans?

Zoledronic Acid, also known as Zometa or Reclast, is generally considered safe and well-tolerated for long-term use in reducing bone complications in cancer patients, though there are rare reports of severe inflammatory reactions, especially in children. ^{2 6 7 8 9}

How does the drug zoledronic acid differ from other treatments for chondrosarcoma?

Zoledronic acid is unique for chondrosarcoma because it is a bisphosphonate that slows tumor growth and increases survival by inhibiting cell proliferation and promoting cell death, unlike traditional surgical treatments that often lead to severe disability and high recurrence rates. ^{1 2 4 5 10}

Research Team

Mohammed Milhem, MBBS

Principal Investigator

University of Iowa

Eligibility Criteria

This trial is for adults with any grade of resectable chondrosarcoma. Participants must have adequate blood counts, liver and kidney function, and not have used osteoclast inhibitors recently. Pregnant or breastfeeding women are excluded, as well as those with severe medical conditions or needing urgent dental surgery.

Inclusion Criteria

- Neutrophil count of >1500/mm

Written informed consent from subject or the subject's legally authorized representative, obtained prior to participation in the study and any related procedures being performed

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

I have not used osteoclast inhibitors for osteoporosis in the last 6 months.

My heart does not function properly.

I have kidney issues that prevent me from using ZA.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive 1 standard dose of IV zoledronic acid prior to surgery, followed by surgery 21-31 days after the dose, and a second dose 3 weeks post-surgery

6 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety, recurrence, and survival with imaging and assessments as per NCCN guidelines

2 years

Regular visits every 6 months

Long-term follow-up

Participants are monitored for overall survival and recurrence-free survival

5 years

Annual visits

Treatment Details

Interventions

• Zoledronic Acid

Trial Overview The study tests the effects of Zoledronic Acid on tumors in patients with chondrosarcoma before they undergo surgery. It's a phase 1b single-arm open-label trial, meaning all participants receive the same treatment without a comparison group.

Participant Groups

Group I: Zoledronic Acid Experimental Treatment 1 Intervention

1 cycle of Zoledronic Acid (ZA) at 4mg IVP prior to surgery and a second cycle of ZA at 4 mg IVP 3 weeks after surgery

Who Is Running the Clinical Trial?

Mohammed Milhem

Lead Sponsor

Trials

9

Recruited

240+

Varun Monga, MD

Lead Sponsor

Trials

7

Recruited

130+

Rising Tide Foundation

Collaborator

Trials

17

Recruited

6,200+

Findings from Research

In a small cohort of four patients with stage IV osteosarcoma, treatment with zoledronic acid (ZA) resulted in a median progression-free survival of 19 months and a median overall survival of over 56 months, indicating its potential efficacy as a treatment option.

Despite prolonged use of ZA for up to 5 years, the patients experienced no significant toxicities and did not require chemotherapy, suggesting that ZA may be a safe long-term treatment for metastatic osteosarcoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zoledronic acid in metastatic osteosarcoma: encouraging progression free survival in four consecutive patients. Conry, RM., Rodriguez, MG., Pressey, JG.[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]

In a study of 28,385 patients with solid tumors or multiple myeloma, treatment with zoledronic acid (ZOL) significantly reduced the incidence of skeletal complications, including a 24% reduction in fractures and a 45% reduction in spinal cord compression.

Patients who continued ZOL treatment for more than 180 days experienced better outcomes, including a 56% reduction in mortality risk, with the most significant benefits seen in those treated regularly for over 18 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the clinical benefit of long-term (beyond 2 years) treatment of skeletal-related events in advanced cancers with zoledronic acid. Henk, H., Teitelbaum, A., Kaura, S.[2018]

Zoledronic acid is the first bisphosphonate proven effective in treating bone metastases in prostate cancer, highlighting its significance in cancer care.

As a potent inhibitor of osteoclast activity, zoledronic acid offers a safe and straightforward administration method, making it a valuable option for managing bone-related complications in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zometa in the treatment of diseminated prostate cancer. Djokic, M.[2019]

Zoledronic acid is effective in reducing skeletal-related events (SREs) such as fractures and spinal cord compression in patients with metastatic bone disease from advanced prostate cancer or renal cell carcinoma, significantly lowering the overall risk of SREs compared to placebo.

In patients with renal cell carcinoma, zoledronic acid not only reduced SREs but also delayed the progression of bone lesions by 5 months, and it has been shown to be safe and well tolerated for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zoledronic acid is effective in preventing and delaying skeletal events in patients with bone metastases secondary to genitourinary cancers. Saad, F., Lipton, A.[2018]

References

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

Zoledronic acid: a review of its use in patients with advanced cancer. [2018]

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

Zoledronic acid in metastatic osteosarcoma: encouraging progression free survival in four consecutive patients. [2022]

3. 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]

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

Zoledronic acid slows down rat primary chondrosarcoma development, recurrent tumor progression after intralesional curretage and increases overall survival. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Zoledronic acid to prevent and treat cancer metastasis: new prospects for an old drug. [2019]

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

Severe non-infective systemic inflammatory response syndrome, shock, and end-organ dysfunction after zoledronic acid administration in a child. [2018]

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

Evaluation of the clinical benefit of long-term (beyond 2 years) treatment of skeletal-related events in advanced cancers with zoledronic acid. [2018]

8. Serbia pubmed.ncbi.nlm.nih.gov

Zometa in the treatment of diseminated prostate cancer. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Zoledronic acid is effective in preventing and delaying skeletal events in patients with bone metastases secondary to genitourinary cancers. [2018]

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

A case report: zoledronic acid-induced anterior uveitis. [2021]