ACTEMRA for Pediatric Craniopharyngioma

Recruiting at 22 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the drug ACTEMRA (tocilizumab) for children and young adults with a type of brain tumor called adamantinomatous craniopharyngioma. Researchers aim to determine if this drug, already used for arthritis, can treat tumors that have returned or grown after surgery or radiation. Children or young adults who have undergone surgery for this tumor or have experienced growth after radiation might be suitable candidates for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that ACTEMRA is likely to be safe for pediatric patients with craniopharyngioma?

Research has shown that tocilizumab is generally safe for people. The FDA has approved it for treating some types of arthritis, indicating its safety for other conditions as well. In studies involving patients with craniopharyngioma, tocilizumab has been used without major safety issues.

For instance, a 15-year-old girl with a type of craniopharyngioma received tocilizumab after several surgeries, and no serious side effects occurred. The drug also effectively reached the tumor area after just one dose, which is promising for its potential use.

While these results are encouraging, safety can vary from person to person. Researchers closely monitor participants in clinical trials for any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for craniopharyngioma?

Unlike the standard treatments for pediatric craniopharyngioma, which often involve surgery and radiation therapy, Tocilizumab offers a new approach by targeting the immune system. This drug is unique because it blocks a specific protein called IL-6, which plays a role in inflammation and tumor growth. Researchers are excited about Tocilizumab because it could potentially reduce tumor-related inflammation and slow down the progression of the disease without the side effects associated with radiation. Additionally, Tocilizumab's mechanism of action provides a novel option for patients who have not responded well to traditional therapies.

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

Research has shown that tocilizumab, a medication that blocks a specific protein involved in inflammation, may help treat adamantinomatous craniopharyngioma (ACP) in children. In one study, a 15-year-old girl with recurring ACP improved after receiving tocilizumab along with other treatments. Another report found that combining tocilizumab with bevacizumab led to even better results, with further tumor improvement. These findings suggest that tocilizumab might help manage ACP by reducing the tumor's size and slowing its growth. While more research is needed, these early results are promising for those seeking new treatment options. Participants in this trial will receive tocilizumab as part of the study's experimental treatment arm, which includes patients with progressive or recurrent ACP following radiation therapy and those who have undergone surgery but have not previously received radiation therapy. ^{1 2 3 6 7}

Who Is on the Research Team?

Maryam Fouladi, MD

Principal Investigator

Nationwide Children's Hospital

Holly Lindsay, MD

Principal Investigator

Children's Hospital Colorado

Todd C Hankinson, MD

Principal Investigator

Children's Hospital Colorado

Are You a Good Fit for This Trial?

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

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 ... We present the case of a 15-year-old girl, with a fifth cystic progression of an adamantinomatous craniopharyngioma after multiple surgeries and previous local ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11183541/

CP-12. PHASE 0 AND FEASIBILITY SINGLE-INSTITUTION ... Systemic delivery of tocilizumab at the established pediatric dosage is promising for treatment of ACP based on preclinical work and its demonstrated ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03970226

NCT03970226 | Tocilizumab in Children With ACP This study will be conducted in two phases. The first phase (phase 0) will be looking at patients with new or recurrent/ progressed craniopharyngioma tumors ...

5. thejns.org thejns.org/caselessons/view/journals/j-neurosurg-case-lessons/9/2/article-CASE24410.xml

Recurrent adamantinomatous craniopharyngioma stabilized ... MRI of the brain 5 months after starting the combination of bevacizumab and tocilizumab showed further improvement in the cystic and nodular ...

6. trials.braintumor.org trials.braintumor.org/trials/NCT05233397

ACTEMRA® for the Treatment of Pediatric Adamantinomatous ... In this Phase II, the drug will be used to treat pediatric patients diagnosed with recurrent Adamantinomatous Craniopharyngioma including patients who have ...

7. thejns.org thejns.org/caselessons/view/journals/j-neurosurg-case-lessons/1/19/article-CASE2150.xml

Adamantinomatous craniopharyngioma associated with a ... Tocilizumab reached ACP tumor tissue and/or cyst fluid after one systemic dose in every patient. LESSONS. This finding helps explain extant data ...