Using tocilizumab to treat children with craniopharyngioma

A Phase 0/Feasibility Trial of Tocilizumab in Children and Adolescents With Newly- Diagnosed or Recurrent/Progressive Adamantinomatous Craniopharyngioma

This study is testing if the drug tocilizumab can help children with a type of brain tumor called craniopharyngioma before surgery and if giving it every two weeks after that can improve their treatment over the next year.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 2 Years to 21 Years
• Sex: All
• Sponsor: University of Colorado, Denver (Academic / other)
• Drugs / interventions: tocilizumab, radiation
• Locations: 1 site (Aurora, Colorado)
• Trial ID: NCT03970226 on ClinicalTrials.gov

What this trial studies

This study investigates the use of tocilizumab in children diagnosed with adamantinomatous craniopharyngioma, focusing on two phases. The first phase aims to determine if a single dose of tocilizumab can effectively penetrate the tumor before standard of care surgery. If successful, the second phase will involve administering tocilizumab every two weeks for up to a year, with patients monitored for up to five years. The study seeks to evaluate the feasibility and potential therapeutic effects of this treatment approach.

Who should consider this trial

Good fit: Ideal candidates include children with newly diagnosed or recurrent adamantinomatous craniopharyngioma who are scheduled for surgical intervention.

Not a fit: Patients with craniopharyngioma who are not candidates for surgery or have other concurrent severe health issues may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for children with craniopharyngioma by enhancing tumor management.

How similar studies have performed: While this approach is novel in the context of craniopharyngioma, similar studies using tocilizumab in other tumor types have shown promising results.

Eligibility criteria

Inclusion Criteria

Phase 0 Eligibility:

1. Tumor biopsy/resection and/or cyst aspiration planned for the clinical care of the patient independent of study participation by the treating pediatric neurosurgeon and neuro-oncologist
2. Must meet one of the following criteria:

   1. Presumed craniopharyngioma based on imaging features and best judgement of treating medical team (if newly diagnosed)
   2. Previous histologically confirmed ACP that has progressed or recurred at the time of enrollment

Feasibility Eligibility:

1. Must meet one of the following criteria:

   1. Recurrent or progressive\* ACP treated with surgery alone without radiation
   2. Recurrent or progressive\* ACP treated with surgery and radiation

      \* Progressive disease for eligibility purposes will be defined as follows: Solid disease: any growth deemed progression based on discretion of the investigator regardless of timing from RT Cystic disease: must be at least 6 months from last day of RT. Patients demonstrating isolated cyst growth \>6 months after RT must show a continued increase in the cystic component on two serial MRI scans performed at least 4 weeks apart OR at least partial reaccumulation of the cyst following one or more cyst aspirations.
   3. Newly diagnosed, by histology or imaging ACP with unresectable residual cystic and/or solid disease that is measurable in 2 dimensions
2. Subjects who participated in the Phase 0 portion and meet eligibility, may enroll in the Feasibility Phase of the study once open.

Overall Study Inclusion Criteria:

1. Age: ≥ 2 years and \< 21 years
2. Subjects may have received prior tocilizumab or other IL6 or IL6R inhibitor
3. Organ Function Requirements

   1. Adequate bone marrow function defined as:

      * Platelet count ≥100,000/μl (transfusion independent)
      * Absolute neutrophil count (ANC) ≥1500/μl
   2. Adequate renal function defined as:

      * Creatinine clearance or radioisotope GFR ≥70 ml/min/1.73 m2 or
      * A serum creatinine based on age/gender as follows: (Age, Male, Female) 3 to \< 6 years, 0.8, 0.8; 6 to \< 10 years, 1, 1; 10 to \< 13 years, 1.2, 1.2; 13 to \< 16 years, 1.5, 1.4; 16 years to \< 18 years, 1.7, 1.4
   3. Adequate liver function defined as:

      * SGOT (AST) and SGPT (ALT) \<1.5x ULN for age
4. Subjects must meet one of the following performance scores:

   1. ECOG performance status scores of 0, 1, or 2;
   2. Karnofsky score of ≥60 for patients \> 16 years of age; or
   3. Lansky score of ≥60 for patients ≤16 years of age
5. 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.
6. Informed consent and assent obtained as appropriate.

Exclusion Criteria

1. Pregnant or breastfeeding
2. Uncontrolled intercurrent illness including, but not limited to:

   1. ongoing or active infection (including active tuberculosis)
   2. symptomatic congestive heart failure
   3. unstable angina pectoris
   4. cardiac arrhythmia
   5. psychiatric illness/social situations that would limit compliance with study requirements are not eligible.
3. Known hypersensitivity or history of anaphylaxis to tocilizumab
4. Received any live vaccinations within 3 months prior to start of therapy
5. Evidence of metastatic disease or other cancer
6. Inability to return for follow up visits or obtain required follow-up studies to assess toxicity of therapy

Where this trial is running

Aurora, Colorado

• Children's Hospital Colorado — Aurora, Colorado, United States (Recruiting)

Study contacts

• Principal investigator: Margaret Macy, MD — Children's Hospital Colorado
• Study coordinator: Ashley Mettetal

Conditions Adamantinomatous Craniopharyngioma; Phase 0; Feasibility; Tocilizumab