Zoledronic Acid for Giant Cell Tumor of Bone

Recruiting at 15 trial locations

Overseen By Allison Gruender, RN

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: St. Louis University

Must not be taking: Bisphosphonates, Denosumab

Disqualifiers: Recurrent GCT, Non-extremity location, others

Stay on Your Current Meds You can continue your current medications while participating

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 3

120 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a special bone cement with a drug to see if it can help prevent giant cell tumors of bone from coming back after surgery. The cement is applied during surgery to kill any remaining tumor cells and make the bone stronger. The drug is known for its ability to inhibit bone resorption and has shown antitumor activity in various cancers.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had previous systemic bisphosphonate or denosumab therapy.

What data supports the effectiveness of the drug Zoledronic Acid for treating Giant Cell Tumor of Bone?

Research shows that using Zoledronic Acid, especially with artificial bone, can help control giant cell tumors of bone by causing tumor cell death and reducing recurrence. In one study, patients treated with Zoledronic Acid and artificial bone showed significant tumor necrosis, while another study found that intravenous Zoledronic Acid helped prevent tumor recurrence and reduced the need for major surgery. ^{1 2 3 4 5}

Is Zoledronic Acid safe for humans?

Zoledronic Acid, also known as Zometa or Reclast, is generally safe and well-tolerated in humans. Common side effects include flu-like symptoms, fatigue, and bone pain, but it has been used safely in various conditions like bone metastases and hypercalcemia of malignancy. ^{3 6 7 8 9}

How does the drug zoledronic acid differ from other treatments for giant cell tumor of bone?

Zoledronic acid is unique because it is a bisphosphonate that inhibits bone resorption, which can help reduce the recurrence of giant cell tumors of bone. Unlike standard surgical treatments, it can be administered intravenously or locally, sometimes with artificial bone, to enhance its effectiveness in controlling the tumor. ^{1 3 4 10 11}

Eligibility Criteria

This trial is for adults with a primary benign giant cell tumor of bone located in an arm or leg, who haven't had bisphosphonate or denosumab therapy before. The tumor must be treatable by removing it and reconstructing the area. It's not for children, pregnant individuals, those with recurring tumors, extensive tumors unsuitable for this treatment approach, or non-extremity tumors.

Inclusion Criteria

My cancer is in an arm or leg.

I have not taken bisphosphonates or denosumab before.

My lesion can be treated by removing it while keeping one solid piece of bone intact.

Exclusion Criteria

My bone cancer has come back.

My cancer is not located in my arms or legs.

My lesion cannot be treated by direct injection due to its size or impact on bones or joints.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Treatment

Participants undergo surgical procedure with or without bisphosphonate treatment

Immediate postoperative period

1 visit (in-person)

Follow-up

Participants are monitored for recurrence, wound healing, and complications

2 years

Visits at 2 weeks, 6 weeks, and every 3 months

Treatment Details

Interventions

• Zoledronic Acid

Trial Overview The study tests if applying Zoledronic Acid directly to the site where a giant cell bone tumor was removed can prevent it from returning. This local treatment is compared to just surgically removing the tumor without any additional medication.

Participant Groups

Group I: Bisphosphonate group Experimental Treatment 1 Intervention

In Arm 2, the bisphosphonate group, 4 mg of zoledronic acid (Zometa) will be added to each bag of bone cement.

Group II: Control group Active Control 1 Intervention

The surgical procedure for all patients will include extensive curettage of the lesion to remove macroscopic tumor, high-speed burring of the residual cavity, adjuvant treatment to the residual cavity, followed by packing of the cavity with either polymethylmethacrylate (PMMA) bone cement (Simplex P; Stryker, Mahwah, New Jersey) alone or bone cement with subchondral allograft bone graft. The choice of cavity reconstruction will be at the discretion of the treating surgeon. Traditional local adjuvants (argon beam coagulation, phenol, ethanol, or cryotherapy) will be used depending on surgeon preference. In addition to the above standard treatment, the patients will be randomized into one of two study arms. In Arm 1, the control group, no additional local therapy will be utilized.

Who Is Running the Clinical Trial?

St. Louis University

Lead Sponsor

Trials

197

Recruited

41,400+

Orthopaedic Research and Education Foundation

Collaborator

Trials

2

Recruited

160+

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

University of California

Collaborator

Trials

46

Recruited

208,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

All India Institute of Medical Science

Collaborator

Trials

1

Recruited

120+

American Academy of Orthopaedic Surgeons

Collaborator

Trials

2

Recruited

430+

McGill University Health Centre/Research Institute of the McGill University Health Centre

Collaborator

Trials

476

Recruited

170,000+

University of Oklahoma

Collaborator

Trials

484

Recruited

95,900+

Findings from Research

Local administration of zoledronic acid, combined with artificial bone, showed promising results in controlling giant cell tumors of bone, with significant tumor necrosis rates in four out of five patients treated.

The study indicates that effective treatment with zoledronic acid requires a bone matrix, as one patient without artificial bone experienced no tumor necrosis and had a local recurrence, highlighting the importance of treatment conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local administration of zoledronic acid for giant cell tumor of bone. Nishisho, T., Hanaoka, N., Miyagi, R., et al.[2018]

The case study demonstrates that intravenous zoledronate, administered at 4 mg every 4 weeks for seven courses, effectively treated a giant cell tumor at the sacrum, leading to no pain, neurological deficits, or local recurrence after two years.

Using zoledronate as a treatment option can significantly reduce the need for major surgical interventions, thereby lowering the associated morbidity in patients with giant cell tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of intravenous bisphosphonate in treatment of giant cell tumor: a case report and review of the literature. Arpornchayanon, O., Leerapun, T.[2022]

In a study of 100 patients with giant cell tumors (GCT) of the proximal tibia, those treated with zoledronic acid (ZA) showed reduced giant cell presence and lower recurrence rates compared to the control group.

The treatment with ZA also led to beneficial histopathological changes, such as increased calcification and fibrosis, indicating its effectiveness in managing GCT, although there was no significant difference in functional outcomes between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Local and Intravenous Zoledronic Acid on Histopathology and Recurrence Rate after Extended Curettage in Giant Cell Tumors of Proximal Tibia: A Prospective Study. Arfee, S., Malik, AT., Nehru, A., et al.[2022]

Intravenous zoledronic acid significantly reduced pain levels in patients with giant cell tumor of bone, as indicated by a decrease in the Visual Analog Scale (VAS) score from 5.33 to 1.8, and increased mineralization around the tumor site.

The treatment also led to a substantial increase in the mean apoptotic index in the bisphosphonate group compared to the control group, suggesting that zoledronic acid effectively induces tumor cell death without significant side effects, making it a beneficial adjuvant therapy before surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of intravenous zoledronic acid in management of giant cell tumor of bone- A prospective, randomized, clinical, radiological and electron microscopic analysis. Dubey, S., Rastogi, S., Sampath, V., et al.[2022]

In a phase II clinical trial involving 24 patients, the use of zoledronic acid (ZOL) after intra-lesional curettage for giant cell tumours (GCT) resulted in a local recurrence rate of 15%, indicating a potential benefit in reducing recurrences, although it did not completely prevent them.

Eighteen out of 20 patients experienced mild side effects from ZOL, but no serious adverse effects were reported, suggesting that the treatment is generally well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant treatment with zoledronic acid after extensive curettage for giant cell tumours of bone. Gouin, F., Rochwerger, AR., Di Marco, A., et al.[2018]

Zoledronic acid is effective in reducing skeletal-related events (SREs) in patients with multiple myeloma and bone metastases, showing a significant delay in the onset of complications compared to pamidronic acid, particularly in breast cancer patients with osteolytic lesions.

The drug is well tolerated and has a similar safety profile to pamidronic acid, with common side effects including flu-like symptoms and fatigue, making it a suitable option for routine use in managing bone complications in advanced malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zoledronic acid: a review of its use in the management of bone metastases and hypercalcaemia of malignancy. Wellington, K., Goa, KL.[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]

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 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]

In a study of 37 patients with giant cell tumors (GCT) of the bone, the use of zoledronic acid before surgical treatment led to significant changes in histopathology, including reduced numbers of giant cells and altered stromal cell morphology, which facilitated easier surgical curettage.

The recurrence rate of GCT was lower in patients who received zoledronic acid (1 out of 18) compared to those who did not (4 out of 19), suggesting that zoledronic acid may effectively reduce the likelihood of tumor recurrence after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Intravenous Zoledronic Acid on Histopathology and Recurrence after Extended Curettage in Giant Cell Tumors of Bone: A Comparative Prospective Study. Kundu, ZS., Sen, R., Dhiman, A., et al.[2022]

Zoledronic acid can be effectively released from acrylic bone cement, with the highest release occurring within the first 24 hours, making it a promising local treatment for tumors like giant cell tumor and multiple myeloma.

In vitro tests showed that zoledronic acid significantly inhibits the growth of tumor cells from giant cell tumors, multiple myeloma, and renal cell carcinoma in a dose-dependent manner, indicating its potential as an effective therapeutic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytotoxic effect of zoledronic acid-loaded bone cement on giant cell tumor, multiple myeloma, and renal cell carcinoma cell lines. Zwolak, P., Manivel, JC., Jasinski, P., et al.[2022]

References

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

Local administration of zoledronic acid for giant cell tumor of bone. [2018]

2. Thailand pubmed.ncbi.nlm.nih.gov

Effectiveness of intravenous bisphosphonate in treatment of giant cell tumor: a case report and review of the literature. [2022]

3. India pubmed.ncbi.nlm.nih.gov

Comparison of Local and Intravenous Zoledronic Acid on Histopathology and Recurrence Rate after Extended Curettage in Giant Cell Tumors of Proximal Tibia: A Prospective Study. [2022]

4. India pubmed.ncbi.nlm.nih.gov

Role of intravenous zoledronic acid in management of giant cell tumor of bone- A prospective, randomized, clinical, radiological and electron microscopic analysis. [2022]

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

Adjuvant treatment with zoledronic acid after extensive curettage for giant cell tumours of bone. [2018]

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

Zoledronic acid: a review of its use in the management of bone metastases and hypercalcaemia of malignancy. [2022]

7. 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]

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

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

9. 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]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of Intravenous Zoledronic Acid on Histopathology and Recurrence after Extended Curettage in Giant Cell Tumors of Bone: A Comparative Prospective Study. [2022]

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

Cytotoxic effect of zoledronic acid-loaded bone cement on giant cell tumor, multiple myeloma, and renal cell carcinoma cell lines. [2022]