Zoledronic Acid for Giant Cell Tumor of Bone

Recruiting at 17 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding zoledronic acid (also known as Zometa or Reclast) to bone cement can prevent a type of bone tumor, called a giant cell tumor, from returning after surgery. The researchers aim to determine if using this drug during surgery is more effective at preventing tumor recurrence than surgery alone. Suitable candidates for this trial have a benign giant cell tumor in an arm or leg and have not received certain bone treatments before. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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.

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

Research has shown that zoledronic acid is generally safe for people. This medication is approved for treating conditions like high calcium levels in cancer patients and osteoporosis in postmenopausal women, indicating thorough safety testing.

In studies, some patients experienced side effects such as fever, tiredness, and flu-like symptoms after taking zoledronic acid. However, these side effects are usually mild, and serious side effects are rare. One study found zoledronic acid to be a safe and more affordable option for treating giant cell tumor of bone compared to other treatments.

While no treatment is completely risk-free, existing research suggests that zoledronic acid is a safe choice for patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for giant cell tumor of bone?

Researchers are excited about using zoledronic acid for treating giant cell tumors of bone because it introduces a new approach to managing this condition. Unlike traditional treatments, which primarily involve surgical removal of the tumor and local adjuvants like argon beam coagulation or cryotherapy, zoledronic acid is a bisphosphonate that targets bone resorption. This means it could potentially reduce the tumor's ability to degrade bone, offering a novel mechanism of action that complements surgical intervention. By incorporating zoledronic acid into bone cement, this treatment has the potential to enhance local control of the tumor and improve outcomes for patients.

What evidence suggests that zoledronic acid might be an effective treatment for giant cell tumor of bone?

Research has shown that zoledronic acid might help prevent giant cell tumors of bone (GCTB) from recurring after surgery. In this trial, participants in the bisphosphonate group will receive zoledronic acid added to bone cement during surgery. A review of several studies suggests that zoledronic acid can lower the risk of tumor recurrence. It also appears to reduce the number and strength of GCTB cells. However, researchers are still determining the optimal dose and method for using zoledronic acid. While the results are promising, further studies are needed to confirm its benefits in treating GCTB. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

All India Institute of Medical Sciences

Collaborator

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+

Published Research Related to This Trial

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]

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]

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]

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) 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]

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]

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 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]

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]

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]

Citations

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pmc.ncbi.nlm.nih.gov/articles/PMC6656477/

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Adjuvant treatment with zoledronic acid did not decrease the recurrence rate of giant cell tumor of bone (GCTB) in this study. The efficacy could not be ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S2212137422000318

Denosumab versus zoledronic acid in cases of surgically ...

The present study indicates that denosumab promotes the deposition of new bone more effectively than zoledronic acid. Additionally, the optimal dosage and ...

3.

journals.lww.com

journals.lww.com/co-oncology/fulltext/2020/07000/current_concepts_in_the_treatment_of_giant_cell.14.aspx

Current concepts in the treatment of giant cell tumour of bone

Zoledronic acid demonstrated higher cytotoxic effect on GCTB stromal cells and RCC than on multiple myeloma, and decrease in number of viable cells was seen in ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8403108/

Role of Zoledronic Acid Supplementation in Reducing Post ...

The current meta-analysis suggests that zoledronic acid supplementation reduces tumor recurrence rates in surgically treated GCTB.

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clinicaltrials.gov

clinicaltrials.gov/study/NCT00264420

NCT00264420 | Safety and Efficacy Study of Concomitant ...

Bisphosphonates are used in bone metastases to keep the cancerous lesion under control in the bone and to help prevent calcium level elevations in the blood.

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mayoclinic.org/drugs-supplements/zoledronic-acid-intravenous-route/description/drg-20066951

Zoledronic acid (intravenous route) - Side effects & uses

Zoledronic acid injection is used to treat hypercalcemia (high levels of calcium in the blood) that may occur in patients with some types of cancer.

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clinicaltrials.gov/study/NCT01564121

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The giant cell tumor (GTC) is an aggressive benign bone tumor, growing at the metaphyseal-epiphyseal regions of long bones, especially around ...

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aetna.com

aetna.com/cpb/medical/data/500_599/0524.html

Zoledronic Acid - Medical Clinical Policy Bulletins

Aetna considers zoledronic acid 5mg injection (Reclast or generic) medically necessary for the following indications: Postmenopausal osteoporosis.