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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how zoledronic acid (also known as Zometa or Reclast) affects tumors in patients with chondrosarcoma, a type of bone cancer, before surgery. The aim is to determine if this treatment can shrink the tumors. Participants will receive zoledronic acid through an IV before and after surgery. The trial seeks participants diagnosed with chondrosarcoma who have not previously taken zoledronic acid. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

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.

Is there any evidence suggesting that zoledronic acid is likely to be safe for humans?

Research has shown that zoledronic acid is generally well-tolerated. One study found it safe and effective for relieving pain in patients with metastatic chondrosarcoma, a type of bone cancer. Another study reported no major side effects, although a small number of patients (4.8%) discontinued treatment due to side effects.

Further research indicates that zoledronic acid can be safely combined with other cancer treatments, such as chemotherapy, without exceeding safe dose limits. This suggests that zoledronic acid is a promising option for managing chondrosarcoma, with generally manageable side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for chondrosarcoma, which often involve surgery and chemotherapy, Zoledronic Acid offers a distinctive approach by targeting bone metabolism. Researchers are excited about this treatment because it uses Zoledronic Acid, a bisphosphonate that works by inhibiting the activity of osteoclasts, the cells responsible for bone breakdown. This mechanism is different from traditional therapies and could potentially reduce tumor growth and improve surgical outcomes. Additionally, the administration of Zoledronic Acid both before and after surgery may enhance its effectiveness, offering a new hope for patients with this challenging condition.

What evidence suggests that zoledronic acid might be an effective treatment for chondrosarcoma?

Research has shown that zoledronic acid, which participants in this trial will receive, may help treat bone-related conditions. Some studies suggest it can reduce pain from bone tumors like chondrosarcoma, even if the tumors do not shrink. In animal studies, this treatment slowed tumor growth and reduced the spread of cancer to the lungs. For patients with bone cancer that has spread from other types of cancer, zoledronic acid lowered the risk of fractures by 40%. While not yet proven for chondrosarcoma, these findings suggest it might help manage the disease. ^{1 3 4 5 6}

Who Is on the Research Team?

Mohammed Milhem, MBBS

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

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

- Serum sodium ≥ LLN

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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/PMC2631458/

Zoledronic acid in metastatic chondrosarcoma and advanced ... Control of pain associated with bone tumors such as chondrosarcoma and chondroma may significantly improve from use of zoledronic acid, independently from tumor ...

2. withpower.com withpower.com/trial/phase-1-chondrosarcoma-6-2017-0ca55

Zoledronic Acid for Chondrosarcoma · Info for Participants 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 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0959804913002219

Feasibility and dose discovery analysis of zoledronic acid ... ZA has been shown to inhibit primary tumour growth, reduce lung metastases and prolong survival in animal models of osteosarcoma.15, 16, 17, 18 Bisphosphonates ...

4. aacrjournals.org aacrjournals.org/clincancerres/article/9/7/2394/203561/Approval-Summary-for-Zoledronic-Acid-for-Treatment

Approval Summary for Zoledronic Acid for Treatment of ... Results from the 1648 randomized patients demonstrated that 4 mg of Zol are effective in decreasing the skeletal morbidity of myeloma and of breast cancer ...

5. researchgate.net researchgate.net/publication/23788213_Zoledronic_acid_in_metastatic_chondrosarcoma_and_advanced_sacrum_chordoma_Two_case_reports

(PDF) Zoledronic acid in metastatic chondrosarcoma and ... In the first case, zoledronic acid was able to maintain pain control despite disease progression following chemotherapy, in the other case, ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17472506/

Zoledronic acid treatment at home: safety data from an ... No acute major side effects were observed during the treatment, and the treatment had to be interrupted for side effects in 2 patients (4.8%). One patient had ...