ACTEMRA for Pediatric Craniopharyngioma

Recruiting at 20 trial locations

Overseen By Amy K Jones, MSN

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Nationwide Children's Hospital

Must not be taking: Investigational drugs, Anti-cancer agents

Disqualifiers: Pregnancy, Gastrointestinal disease, Infections, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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: 2

Duration: 104 weeks

38 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests ACTEMRA, a drug that blocks a protein called IL-6, in children with a recurring brain tumor called ACP. The goal is to see if it can reduce tumor growth and improve their quality of life.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before enrolling. You must not be on any other investigational drugs or anti-cancer agents, and if you're taking corticosteroids, your dose must be stable or decreasing for at least 7 days before joining the trial.

What data supports the effectiveness of the drug Tocilizumab for treating pediatric craniopharyngioma?

Research shows that Tocilizumab, which targets a protein called IL-6R involved in tumor growth, helped reduce tumor size in two patients with recurrent cystic craniopharyngioma. Another case reported that Tocilizumab stabilized the tumor in a child, suggesting it may be a promising option to reduce the need for surgery and radiation. ^{1 2 3 4 5}

How is the drug Tocilizumab unique in treating pediatric craniopharyngioma?

Tocilizumab is unique because it targets the interleukin-6 receptor (IL-6R), which is found in high levels in craniopharyngioma tumors, offering a new approach compared to traditional surgery and radiation. This drug, administered intravenously, has shown promise in reducing tumor cysts, potentially decreasing the need for more invasive treatments. ^{1 3 4 5 6}

Research Team

Maryam Fouladi, MD

Principal Investigator

Nationwide Children's Hospital

Todd C Hankinson, MD

Principal Investigator

Children's Hospital Colorado

Holly Lindsay, MD

Principal Investigator

Children's Hospital Colorado

Eligibility Criteria

This trial is for children and young adults aged between 1 to 25 years with confirmed adamantinomatous craniopharyngioma, a type of brain tumor. They must have measurable disease, be stable post-surgery or radiation therapy, and not have received certain treatments recently. Patients with controlled seizures can join but those with uncontrolled infections or recent vaccinations cannot.

Inclusion Criteria

My hemoglobin level is above 8 g/dL.

Patients must have measurable disease.

It has been over 3 weeks since my last monoclonal antibody treatment.

Exclusion Criteria

I do not have any major health issues that could affect my safety or participation in the study.

I had surgery less than 6 weeks ago or am worried about how my surgical wound is healing.

I have a history of serious gastrointestinal issues like IBD or a perforated gut.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tocilizumab at the dose approved for pediatric Systemic Juvenile Idiopathic Arthritis for up to two years

104 weeks

IV administration every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Tocilizumab

Trial Overview The study tests ACTEMRA (tocilizumab), an IL-6 receptor antagonist already used in arthritis, on pediatric patients who've had surgery and/or radiation for recurrent adamantinomatous craniopharyngioma. It's a Phase II trial to see how effective this drug is in treating this specific brain tumor.

Participant Groups

Group I: Stratum 1 and Stratum 2 Experimental Treatment 1 Intervention

Stratum 1: Patients with progressive or recurrent adamantinomatous craniopharyngiomas following radiation therapy. Stratum 2: Patients with measurable adamantinomatous craniopharyngioma who have undergone surgery but have not previously received radiation therapy. Progressive disease is allowed but not required

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?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

Children's Hospital Colorado

Collaborator

Trials

121

Recruited

5,135,000+

Findings from Research

Tocilizumab, a monoclonal antibody targeting IL-6R, showed significant efficacy in reducing cyst burden in two pediatric patients with recurrent cystic adamantinomatous craniopharyngioma (ACP), suggesting it may be a promising treatment option for this condition.

The study highlights the potential of targeting IL-6R in ACP, a common pediatric brain tumor, as conventional therapies often have limited efficacy and significant side effects, particularly in recurrent cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting IL-6 Is a Potential Treatment for Primary Cystic Craniopharyngioma. Grob, S., Mirsky, DM., Donson, AM., et al.[2020]

Pediatric adamantinomatous craniopharyngiomas (ACPs) are benign but aggressive brain tumors that can lead to significant neuroendocrine issues, making the search for safer and more effective treatments crucial.

Recent studies have identified several potential therapeutic targets, such as IL-6 and PD1/PD-L1, and ongoing clinical trials are exploring the efficacy of agents that target these pathways, which could significantly improve treatment outcomes and reduce patient morbidity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adamantinomatous craniopharyngioma in the molecular age and the potential of targeted therapies: a review. Whelan, R., Hengartner, A., Folzenlogen, Z., et al.[2021]

In a phase 0 trial involving 3 children with adamantinomatous craniopharyngioma (ACP), a single intravenous dose of tocilizumab successfully reached the tumor tissue and cyst fluid, suggesting its potential role in ACP therapy.

The study indicates that ACP tumors do not reside behind an intact blood-brain barrier, opening up possibilities for a wider range of antitumor therapies to be tested in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adamantinomatous craniopharyngioma associated with a compromised blood-brain barrier: patient series. Prince, EW., Hoffman, LM., Vijmasi, T., et al.[2022]

A 15-year-old girl with a recurrent adamantinomatous craniopharyngioma was successfully treated with biweekly intravenous tocilizumab, which stabilized her cyst and improved her quality of life after multiple surgeries and radiotherapy.

Tocilizumab, an anti-interleukin-6 agent, shows promise as an immune-modulating treatment for cystic tumors like craniopharyngioma, potentially reducing the need for further surgeries and delaying or avoiding radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab for the fifth progression of cystic childhood craniopharyngioma-a case report. de Vos-Kerkhof, E., Buis, DR., Lequin, MH., et al.[2023]

A study analyzing mRNA gene expression in 15 pediatric adamantinomatous craniopharyngioma (ACP) samples identified several overexpressed pharmaceutical targets, including those for the kinase inhibitor dasatinib and EGFR pathway targets, which could lead to new treatment options.

This research marks the first transcriptome analysis of ACP, providing a foundation for developing targeted pharmacological therapies that could significantly improve the quality of life for children affected by this aggressive brain tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of targets for rational pharmacological therapy in childhood craniopharyngioma. Gump, JM., Donson, AM., Birks, DK., et al.[2018]

The study developed a murine orthotopic craniopharyngioma model (PDX) using xenografts from three patients, allowing for in vivo drug testing and characterization through advanced MRI techniques.

MRI effectively distinguishes between vital and non-vital tumor cells in craniopharyngioma PDX, with specific parameters correlating to tumor vitality, which can aid in evaluating treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of the murine orthotopic adamantinomatous craniopharyngioma PDX model by MRI in correlation with histology. Hölsken, A., Schwarz, M., Gillmann, C., et al.[2018]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Targeting IL-6 Is a Potential Treatment for Primary Cystic Craniopharyngioma. [2020]

2. Germany pubmed.ncbi.nlm.nih.gov

Adamantinomatous craniopharyngioma in the molecular age and the potential of targeted therapies: a review. [2021]

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

Adamantinomatous craniopharyngioma associated with a compromised blood-brain barrier: patient series. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Tocilizumab for the fifth progression of cystic childhood craniopharyngioma-a case report. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Identification of targets for rational pharmacological therapy in childhood craniopharyngioma. [2018]

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

Characterization of the murine orthotopic adamantinomatous craniopharyngioma PDX model by MRI in correlation with histology. [2018]