Tocilizumab for Craniopharyngioma

Overseen By Shandi Watts

Age: < 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Colorado, Denver

Disqualifiers: Pregnant, Active infection, Heart failure, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 27

9 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests if tocilizumab, an anti-inflammatory drug, can reach and affect brain tumors in patients with craniopharyngioma. If successful, patients will receive the drug regularly over several months to see if it helps control their tumors.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is tocilizumab generally safe for humans?

Tocilizumab, also known as Actemra or RoActemra, has been studied for various conditions and is generally considered safe, though it can cause side effects like infections, decreased white blood cells, and elevated liver enzymes. In clinical trials, common side effects included decreased neutrophils (a type of white blood cell), infections, and increased liver enzymes, but these were generally manageable. ^{1 2 3 4 5}

How does the drug tocilizumab differ from other treatments for craniopharyngioma?

Tocilizumab is unique because it is a monoclonal antibody that targets the interleukin-6 receptor, which is involved in immune system regulation and inflammation. This mechanism is different from traditional treatments for craniopharyngioma, which typically involve surgery or radiation. ^{1 2 6 7 8}

Who Is on the Research Team?

Margaret E. Macy

Principal Investigator

Children's Hospital Colorado

Are You a Good Fit for This Trial?

This trial is for children and young adults (2 to <21 years old) with a type of brain tumor called craniopharyngioma. It's open to those with new, recurrent, or progressive tumors that haven't been fully removed by surgery or have come back after treatment. Participants need functioning major organs and acceptable blood counts, must not be pregnant or breastfeeding, and should agree to use birth control.

Inclusion Criteria

My kidney function, based on my age and gender, meets the required levels.

My kidney function is normal.

Subjects of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study.

Exclusion Criteria

Pregnant or breastfeeding

I have an irregular heartbeat.

psychiatric illness/social situations that would limit compliance with study requirements are not eligible.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 0

Patients receive one dose of tocilizumab before SOC surgery to assess drug penetration in the tumor

1 day

1 visit (in-person)

Feasibility Phase

Patients receive tocilizumab every two weeks for up to 13 cycles (approximately 1 year)

1 year

26 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Tocilizumab

Trial Overview The study tests Tocilizumab in two phases: Phase 0 checks if the drug reaches the tumor when given before standard surgery. If successful, Phase 1 gives Tocilizumab every two weeks for up to a year to see how well it works as a treatment. Patients can move from Phase 0 to Phase 1 and will be monitored for five years.

How Is the Trial Designed?

Group I: Tocilizumab Administration: Phase 0 Experimental Treatment 1 Intervention

In Phase 0, patients will receive one dose of tocilizumab prior to surgery.

Group II: Tocilizumab Administration: Feasibility Phase Experimental Treatment 1 Intervention

During the Feasibility Phase, patients will receive tocilizumab every 2 weeks for up to 13 cycles (approximately 1 year). Patients will be followed for up to 5 years.

Tocilizumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

Approved in United States as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

Approved in Canada as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

Approved in Japan as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Tocilizumab is a humanized monoclonal antibody that targets the interleukin-6 receptor, showing efficacy in treating conditions like Castleman disease and various types of arthritis, with approval in Japan and the European Union for these uses.

The drug is currently under review by the US FDA for moderate-to-severe rheumatoid arthritis and has potential applications for other IL-6 related disorders, such as Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab. Venkiteshwaran, A.[2021]

Tocilizumab is an effective treatment for systemic and polyarticular juvenile idiopathic arthritis (JIA) in children aged 2 years and older, showing significant improvement in patient responses compared to placebo in two phase III trials involving patients aged 2-17 years.

The drug was generally well tolerated, with infections being the most common adverse events; however, there was an approximately 11% annual risk of serious infections, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab: a review of its use in the treatment of juvenile idiopathic arthritis. Frampton, JE.[2021]

The biosimilar BAT1806 demonstrated bioequivalence to the reference products RoActemra-EU and Actemra-US in a study involving 129 healthy Chinese men, with pharmacokinetic parameters falling within the predefined bioequivalence limits.

Both BAT1806 and the reference products showed similar safety profiles, with low intersubject variability and comparable rates of treatment-related adverse events, primarily affecting blood cell counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Clinical Study Comparing the Tolerance, Immunogenicity, and Pharmacokinetics of Proposed Biosimilar BAT1806 and Reference Tocilizumab in Healthy Chinese Men. Zhang, H., Wang, H., Wei, H., et al.[2021]

CT-P47, a biosimilar to tocilizumab, showed pharmacokinetic equivalence to the reference drug EU-tocilizumab in a study involving 289 healthy adults, indicating similar absorption and concentration levels in the body after administration.

The study found that CT-P47 was well tolerated, with comparable safety and immunogenicity profiles to EU-tocilizumab, suggesting it could be a safe alternative for patients requiring tocilizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of candidate tocilizumab biosimilar CT-P47 versus reference tocilizumab: a randomized, double-blind, single-dose phase I study. Yu, KS., Kim, B., Shin, D., et al.[2023]

The proposed biosimilar HS628 demonstrated pharmacokinetic similarity to the reference drug tocilizumab (Actemra®) in a study involving 80 healthy Chinese male subjects, with key parameters falling within the predefined bioequivalence range of 80%-125%.

HS628 showed a similar safety profile to tocilizumab, with no significant differences in treatment-emergent adverse events, indicating that it may be a safe alternative for patients requiring this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study comparing the pharmacokinetics and safety of HS628 (tocilizumab biosimilar) and reference tocilizumab in healthy male subjects. Qian, H., Cheng, J., Gui, Y., et al.[2023]

Tocilizumab (TCZ), a monoclonal antibody used for rheumatological diseases, has been linked to the development of recurrent aphthous mouth ulcers in two patients, marking the first report of this side effect.

The ulcers resolved after stopping TCZ and recurred upon re-administration, indicating a direct causal relationship; however, TCZ's mechanism of action, which inhibits a pro-inflammatory cytokine, makes this side effect unexpected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Persistent aphthous mouth ulcers associated with tocilizumab: two cases]. Samimi, M., Lauferon, F., Hüttenberger, B., et al.[2016]

Tocilizumab is an effective treatment for adults with moderate to severe rheumatoid arthritis (RA), showing beneficial effects on disease symptoms and quality of life, based on several large clinical trials and studies.

Long-term use of tocilizumab (up to 9 years) is generally well tolerated, with infections being the most common side effect, and it has been shown to be more effective than adalimumab in patients who cannot continue methotrexate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous tocilizumab: a review of its use in adults with rheumatoid arthritis. Dhillon, S.[2022]

Tocilizumab, an anti-IL-6 agent, shows potential benefits in treating certain juvenile-onset rheumatic diseases, particularly in halting disease progression in juvenile scleroderma and providing promising outcomes in childhood Takayasu arteritis.

While tocilizumab is effective in preventing systemic inflammation in Kawasaki's disease, it carries a risk of developing coronary aneurysms, highlighting the need for careful monitoring in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-label use of tocilizumab to treat non-juvenile idiopathic arthritis in pediatric rheumatic patients: a literature review. Jung, JY., Kim, MY., Suh, CH., et al.[2020]

Citations

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

Tocilizumab. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Tocilizumab: a review of its use in the treatment of juvenile idiopathic arthritis. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

A Phase I Clinical Study Comparing the Tolerance, Immunogenicity, and Pharmacokinetics of Proposed Biosimilar BAT1806 and Reference Tocilizumab in Healthy Chinese Men. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of candidate tocilizumab biosimilar CT-P47 versus reference tocilizumab: a randomized, double-blind, single-dose phase I study. [2023]

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

A phase I study comparing the pharmacokinetics and safety of HS628 (tocilizumab biosimilar) and reference tocilizumab in healthy male subjects. [2023]

6. France pubmed.ncbi.nlm.nih.gov

[Persistent aphthous mouth ulcers associated with tocilizumab: two cases]. [2016]

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

Intravenous tocilizumab: a review of its use in adults with rheumatoid arthritis. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Off-label use of tocilizumab to treat non-juvenile idiopathic arthritis in pediatric rheumatic patients: a literature review. [2020]