What is the mechanism of action of this treatment?

Bisphosphonates, commonly used in the treatment of Giant Cell Tumor (GCT), work by inhibiting osteoclast-mediated bone resorption. This mechanism is crucial for GCT patients because these tumors are characterized by aggressive bone destruction due to the activity of osteoclast-like giant cells. By inhibiting these cells, bisphosphonates can help reduce bone resorption, potentially decreasing the recurrence rate of the tumor and preserving bone integrity. This can lead to better surgical outcomes and lower the risk of tumor recurrence, which is vital for the long-term management of GCT.

What side effects are associated with this type of intervention?

The most common side effects of bisphosphonate treatments, which are being studied for local delivery in Giant Cell Tumor of bone, include osteonecrosis of the jaw, hypocalcemia, renal insufficiency, acute phase responses (flu-like symptoms), ocular toxicities, musculoskeletal pain, and atrial fibrillation. These side effects are consistent with those observed in broader applications of bisphosphonates in cancer patients and other conditions involving bone resorption.

What prior FDA approvals exist?

The FDA has approved denosumab, a RANK ligand inhibitor, for the treatment of Giant Cell Tumor of bone. Denosumab works by inhibiting osteoclast-mediated bone resorption, similar to bisphosphonates. This approval provides a non-surgical option for patients with GCT, particularly those who are not candidates for surgery or have recurrent tumors. Bisphosphonates, while not specifically approved for GCT, are being studied for their potential to reduce recurrence rates when used as a surgical adjuvant.

What other types of research exist?

Promising alternatives to local delivery of bisphosphonate for giant cell tumor patients include denosumab, a monoclonal antibody that inhibits RANKL, thereby preventing osteoclast formation and activity. Denosumab has shown efficacy in reducing tumor size and preventing recurrence. Additionally, targeted therapies and immunotherapies are being explored, though they are still in early stages of research.

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Zoledronic Acid for Giant Cell Tumor of Bone

Phase 3

Recruiting

Research Sponsored by St. Louis University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Lesion located in an extremity

No previous systemic bisphosphonate or denosumab therapy

Must not have

Recurrent GCT of bone

Previous systemic bisphosphonate or denosumab therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up follow-ups will consist of clinical visits. the clinical visits will be at 2 weeks postoperatively, 6 weeks postoperatively, and then every three months for the first two years after surgery.

Awards & highlights

Pivotal Trial

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While specific side effects are not listed here, bisphosphonates like Zoledronic Acid may generally cause flu-like symptoms, pain at the injection site, nausea, and occasionally affect kidney function or cause jawbone problems.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer is in an arm or leg.

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I have not taken bisphosphonates or denosumab before.

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I have a non-cancerous tumor in my bone.

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

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My bone cancer has come back.

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I have been treated with bisphosphonates or denosumab before.

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

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I am not pregnant and do not plan to become pregnant during the trial. I do not have children participating in this trial.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ follow-ups will consist of clinical visits. the clinical visits will be at 2 weeks postoperatively, 6 weeks postoperatively, and then every three months for the first two years after surgery.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~follow-ups will consist of clinical visits. the clinical visits will be at 2 weeks postoperatively, 6 weeks postoperatively, and then every three months for the first two years after surgery.

This trial's timeline: 3 weeks for screening, Varies for treatment, and follow-ups will consist of clinical visits. the clinical visits will be at 2 weeks postoperatively, 6 weeks postoperatively, and then every three months for the first two years after surgery. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

The endpoint for patient participation will be local recurrence

Secondary study objectives

MSTS Score

Potential bisphosphonate complications related to systemic administration

Surgical site infection

+1 more

Side effects data

From 2020 Phase 4 trial • 61 Patients • NCT03087851

90%

Infection (unspecified) + Musculoskeletal symptoms

40%

Flu-like symptoms after ZOL treatment

10%

Fracture

Cancer

100%

80%

60%

40%

20%

Study treatment Arm

9-months Group

Observation Group

6-month Group

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Bisphosphonate groupExperimental Treatment1 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 groupActive Control1 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Zoledronic acid

FDA approved

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Bisphosphonates, commonly used in the treatment of Giant Cell Tumor (GCT), work by inhibiting osteoclast-mediated bone resorption. This mechanism is crucial for GCT patients because these tumors are characterized by aggressive bone destruction due to the activity of osteoclast-like giant cells. By inhibiting these cells, bisphosphonates can help reduce bone resorption, potentially decreasing the recurrence rate of the tumor and preserving bone integrity. This can lead to better surgical outcomes and lower the risk of tumor recurrence, which is vital for the long-term management of GCT.