Glucarpidase for Osteosarcoma

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: OHSU Knight Cancer Institute

Must be taking: Methotrexate

Must not be taking: Glucarpidase

Disqualifiers: Other malignancies, Liver disease, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 10 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether glucarpidase (also known as Voraxaze, carboxypeptidase G2, or Megludase) can reduce the side effects of high-dose methotrexate (HDMTX) in individuals with osteosarcoma, a type of bone cancer. The researchers aim to determine if glucarpidase can lower methotrexate levels in the blood, potentially shortening hospital stays and reducing harmful effects. The trial seeks participants who are newly diagnosed with osteosarcoma and have a treatment plan that includes high doses of methotrexate. As an Early Phase 1 trial, this research focuses on understanding how glucarpidase works in people, offering participants the opportunity to contribute to groundbreaking treatment insights.

Will I have to stop taking my current medications?

The trial requires participants to stop using any medications that significantly interact with methotrexate metabolism or excretion. If you're taking such medications, you may need to discontinue them to participate in the trial.

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

Research has shown that glucarpidase is generally safe, based on case reports and clinical trials. This enzyme lowers high levels of methotrexate, a drug used in cancer treatment. Patients have experienced fewer side effects when glucarpidase manages methotrexate toxicity. Methotrexate commonly causes kidney and liver problems, mouth sores, and blood issues. Glucarpidase reduces the risk of these problems by breaking down methotrexate in the body. Although this treatment is still in early trials for osteosarcoma, current data suggests it is well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for osteosarcoma, which typically involve chemotherapy drugs like methotrexate, glucarpidase offers a unique approach. Glucarpidase is an enzyme designed to rapidly break down and eliminate methotrexate from the body, potentially reducing toxic side effects associated with high-dose methotrexate treatments. Researchers are excited about glucarpidase because it could allow for higher doses of methotrexate to be used more safely, potentially enhancing the overall effectiveness of treatment against osteosarcoma while minimizing harm to patients.

What evidence suggests that glucarpidase might be an effective treatment for reducing toxicity in osteosarcoma patients?

Research has shown that glucarpidase, the treatment under study in this trial, effectively lowers methotrexate levels in the blood. In one study, almost all patients experienced at least an 85% reduction in methotrexate levels after taking glucarpidase. Another study found a reduction of 99% or more in blood methotrexate levels. This suggests that glucarpidase can help mitigate the harmful effects of methotrexate and may shorten hospital stays for patients with osteosarcoma receiving high doses of methotrexate. Early results are promising, indicating that glucarpidase can serve as a non-invasive treatment to counteract methotrexate toxicity. ^{4 5 6 7 8}

Who Is on the Research Team?

Lara Davis, MD

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

This trial is for people with osteosarcoma who haven't had high-dose methotrexate before. They must be in good enough health to handle the treatment, have a certain level of blood cells and organ function, and agree to use birth control. It's not for those with significant liver disease, HIV, or other active cancers (with some exceptions), or women who are pregnant/breastfeeding.

Inclusion Criteria

Platelet count 75,000/mm^3 (or >= 75 x 10^9/L)

Total serum bilirubin =< 2 x ULN

I am 40 or older and considered high-risk.

Exclusion Criteria

Uncontrolled intercurrent illness, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent

Participants with a history of hypersensitivity to Escherichia (E.)coli-derived proteins

I have no other cancers, or they were treated and cured over 2 years ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive high-dose methotrexate (HDMTX) intravenously over 4 hours on day 1 of weeks 4, 5, 9, and 10, followed by glucarpidase administration 24 and 48 hours after each HDMTX infusion

10 weeks

4 visits (in-person) for HDMTX and glucarpidase administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of glucarpidase hypersensitivity and neutralizing antibodies

32 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Glucarpidase

Trial Overview The trial tests glucarpidase's ability to reduce toxicity from high-dose methotrexate in osteosarcoma patients. The goal is to see if it can lower methotrexate levels in the blood, potentially leading to shorter hospital stays and fewer side effects.

How Is the Trial Designed?

Group I: Treatment (glucarpidase) Experimental Treatment 2 Interventions

Patients receive standard of care HDMTX IV over 4 hours on day 1 of weeks 4, 5, 9, and 10. After 24 hours after the start of each HDMTX infusion, patients also receive glucarpidase IV over 5 minutes in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

BTG International Inc.

Collaborator

Trials

43

Recruited

3,100+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Published Research Related to This Trial

A 14-year-old patient with Gaucher disease type III experienced severe allergic reactions to imiglucerase after 9 years of treatment, highlighting that adverse reactions can occur even after long-term use of recombinant enzymes.

Switching to velaglucerase alfa after severe reactions to other treatments resulted in successful management of the patient's condition without premedication, indicating that different recombinant enzymes may have varying safety profiles and efficacy for individual patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzyme Replacement Therapy in a Patient with Gaucher Disease Type III: A Paradigmatic Case Showing Severe Adverse Reactions Started a Long Time After the Beginning of Treatment. Vairo, F., Netto, C., Dorneles, A., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3990659/

Efficacy of Glucarpidase (Carboxypeptidase G2) in Patients ... Regardless of starting methotrexate concentration, nearly all patients experienced a reduction in methotrexate concentration after glucarpidase of at least 85%.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03960177

Glucarpidase After High-Dose Methotrexate in Patients ... This early phase I trial studies how well glucarpidase works in reducing toxicity in patients with osteosarcoma receiving high dose methotrexate treatment.

3. voraxaze.com voraxaze.com/why-voraxaze/efficacy

Voraxaze ® (glucarpidase) EFFICACY Of 476 patients receiving Voraxaze, death occurred in 22% of patients treated after 4 days following HDMTX infusion compared with 10.9% treated within 2 days of ...

4. accpjournals.onlinelibrary.wiley.com accpjournals.onlinelibrary.wiley.com/doi/abs/10.1002/phar.1360

Efficacy of Glucarpidase (Carboxypeptidase G2) in Patients ... Glucarpidase caused a clinically important 99% or greater sustained reduction of serum methotrexate levels and provided noninvasive rescue from methotrexate ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0753332223010831

Glucarpidase (carboxypeptidase G2): Biotechnological ... In a trial with 27 patients, ZD2767P was highly effective when combined with conjugated A5B7 F(ab՜)2-CPG2. ZD2767P exhibited a maximum tolerated dose of 15.5 mg ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3875266/

Glucarpidase (Voraxaze), a Carboxypeptidase Enzyme for ... The drug has demonstrated considerable safety and efficacy through case reports and clinical trials, and it is likely to be incorporated in future protocols for ...

7. voraxaze.com voraxaze.com/resources

Resources The authors report on clinical data and outcomes in pediatric patients who received Voraxaze® (glucarpidase) after treatment with high-dose methotrexate (HDMTX) ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5759822/

Consensus Guideline for Use of Glucarpidase in Patients with ... This guideline provides recommendations to identify the population of patients who would benefit from glucarpidase rescue.