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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores tocilizumab, a medication, to determine its effectiveness in treating craniopharyngioma, a type of brain tumor. In the first phase, researchers aim to discover if the drug can reach the tumor before surgery. If successful, the next phase will test regular doses over a year to evaluate its effectiveness in managing the tumor. Potential participants include those with new or recurring craniopharyngioma tumors, particularly if previous surgery and possibly radiation have not led to improvement. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

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 there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that tocilizumab, also known as ACTEMRA®, has been tested for various health conditions, with some safety concerns noted. For instance, in treating rheumatoid arthritis, patients using tocilizumab faced a higher risk of serious infections, potentially leading to hospitalization or death. However, studies on pediatric brain tumors suggest that tocilizumab might safely and effectively reduce tumor size. Since this study is in an early stage, it primarily examines whether the drug can reach the tumor, resulting in limited safety information specifically for patients with craniopharyngioma. Nonetheless, because tocilizumab is already approved for other uses, it has undergone prior safety testing. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for craniopharyngioma, which often involve surgery and radiation, tocilizumab offers a novel approach by targeting the immune system. Tocilizumab specifically blocks the interleukin-6 (IL-6) receptor, which may play a role in tumor growth and inflammation. Researchers are excited about this treatment because it could reduce tumor size or slow progression with potentially fewer side effects than traditional methods. This unique mechanism of action provides a new avenue for managing craniopharyngioma, especially for patients who may not respond well to existing therapies.

What evidence suggests that tocilizumab might be an effective treatment for craniopharyngioma?

Research suggests that tocilizumab might help treat adamantinomatous craniopharyngioma, a type of brain tumor. In one case, a 7-year-old patient showed stable tumor growth after six months of tocilizumab treatment without any side effects. Another report indicates that tocilizumab could prevent these tumors from regrowing. The treatment works by blocking the IL-6 receptor, a part of the immune system involved in tumor growth. While early evidence shows promise, more research is needed to confirm its effectiveness. Participants in this trial will receive tocilizumab either during the Feasibility Phase, with administration every two weeks for up to 13 cycles, or in Phase 0, with a single dose before surgery. ^{1 2 4 6 7}

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, 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]

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 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]

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]

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 (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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05233397

NCT05233397 | ACTEMRA® for the Treatment of Pediatric ... We hypothesize that the IL6- receptor antagonist ACTEMRA (tocilizumab) will be safe and effective at inducing tumor response in children with residual ACP. In ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10598752/

Tocilizumab for the fifth progression of cystic childhood ... Our case report illustrates TCZ's possible effectiveness in interrupting ACP's repeated cystic growth. This phenomenon may offer new insight ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11734617/

Recurrent adamantinomatous craniopharyngioma stabilized ... After 6 months of treatment with biweekly tocilizumab, the 7-year-old patient had experienced no adverse effects and the cystic component of the ...

4. trials.braintumor.org trials.braintumor.org/trials/NCT05233397

ACTEMRA® for the Treatment of Pediatric Adamantinomatous ... We hypothesize that the IL6- receptor antagonist ACTEMRA (tocilizumab) will be safe and effective at inducing tumor response in children with residual ACP. In ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-03407

Tocilizumab for the Treatment of Progressive or Recurrent ... This phase II trial tests how well tocilizumab works in treating adamantinomatous craniopharyngioma that is growing, spreading and getting worse ...

6. actemrahcp.com actemrahcp.com/ra/clinical-study-safety/clinical-study-safety.html

Rheumatoid Arthritis (RA) Clinical Trial Safety Side Effects Patients treated with ACTEMRA are at increased risk for developing serious infections that may lead to hospitalization or death.

7. cincinnatichildrens.org cincinnatichildrens.org/service/c/clinical-trials/studies/connect1905-032723

CONNECT1905: ACTEMRA® for the Treatment of Pediatric ... We hypothesize that the IL6- receptor antagonist ACTEMRA (tocilizumab) will be safe and effective at inducing tumor response in children with residual ACP.