Glucarpidase for Osteosarcoma

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

12 Participants Needed

Trial Summary

What is the purpose of this trial?

This early phase I trial studies how well glucarpidase works in reducing toxicity in patients with osteosarcoma receiving high dose methotrexate treatment. Glucarpidase may reduce the levels of methotrexate in patients' blood and lead to shorter hospitalizations and a reduction in toxicities.

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.

What data supports the effectiveness of the drug Glucarpidase for treating osteosarcoma?

The research primarily discusses the use of Glucarpidase for treating methotrexate toxicity, which is a different condition. There is no direct evidence provided for its effectiveness in treating osteosarcoma. ^{1 2 3 4 5}

How does the drug glucarpidase differ from other treatments for osteosarcoma?

Glucarpidase is unique because it is an enzyme that rapidly breaks down methotrexate, a common chemotherapy drug, into non-toxic components, helping to prevent kidney damage from high methotrexate levels. This is particularly useful in emergency situations where methotrexate clearance is delayed, unlike other treatments that do not specifically target methotrexate toxicity. ^{6 7 8 9 10}

Research Team

Lara Davis, MD

Principal Investigator

OHSU Knight Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

Length of stay, mortality, and readmissions among Medicare cancer patients treated with glucarpidase and conventional care: a retrospective study. [2023]

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

Glucarpidase (voraxaze), a carboxypeptidase enzyme for methotrexate toxicity. [2021]

3. United States 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. [2021]

4. France pubmed.ncbi.nlm.nih.gov

[Renal toxicity of high-dose methotrexate]. [2018]

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

Long-term clinical outcomes in type 1 Gaucher disease following 10 years of imiglucerase treatment. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Glucarpidase following high-dose methotrexate: update on development. [2022]

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

Delayed Methotrexate Clearance Despite Carboxypeptidase-G2 (Glucarpidase) Administration in 2 Patients With Toxic Methotrexate Levels. [2022]

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

Glucarpidase to combat toxic levels of methotrexate in patients. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Glucarpidase rescue in a patient with high-dose methotrexate-induced nephrotoxicity. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Routine use of low-dose glucarpidase following high-dose methotrexate in adult patients with CNS lymphoma: an open-label, multi-center phase I study. [2022]