Tocilizumab in Children With ACP

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

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. These patients will be given one dose of tocilizumab before they have SOC surgery of their tumor. The objective of this phase is to see if drug reaches the tumor. If phase 0 is favorable and shows that drug is penetrating the tumor, the second phase of the study (feasibility phase) will open. Both phases will remain open concurrently and patients will be able to enroll on the Phase 0 then "roll over" and enroll on the feasibility phase. During the feasibility phase patients will be administered tocilizumab every two weeks for up to 13 cycles (approximately 1 year). Patients will be followed for up to 5 years in the feasibility phase.

Study Overview

• Status: Active, not recruiting
• Conditions: Adamantinomatous Craniopharyngioma
• Intervention / Treatment: Drug: Tocilizumab

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tocilizumab Administration: Phase 0; In Phase 0, patients will receive one dose of tocilizumab prior to surgery.	Drug: Tocilizumab; Phase 0: One dose of tocilizumab prior to surgery Feasibility phase: Tocilizumab administered every 2 weeks for up to 13 cycles (approximately 1 year).; Other Names: Actemra
Experimental: Tocilizumab Administration: Feasibility Phase; 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.	Drug: Tocilizumab; Phase 0: One dose of tocilizumab prior to surgery Feasibility phase: Tocilizumab administered every 2 weeks for up to 13 cycles (approximately 1 year).; Other Names: Actemra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 0: Presence of Tocilizumab and Metabolites	Utilize biopsy and/or drainage to identify the presence of tocilizumab and its metabolites in adamantinomatous craniopharyngioma (ACP) tumor tissue and/or cyst fluid and/or CSF following one dose of systemically administered tocilizumab.	Within 4 to 8 hours of administration of tocilizumab
Feasibility Phase: Toxicity Profile	To define toxicities of tocilizumab therapy using CTCAE version 5.	Start of study to end of study, up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 0: IL6 and Inflammatory Cytokines	To define levels of IL6 and other inflammatory cytokines in biopsied tissue and/or cyst fluid as measured by enzyme-linked immunosorbent assay (ELISA) following 1 dose of systemically administered tocilizumab	Within 4 to 8 hours of administration of tocilizumab
Feasibility Phase: Progression Free Survival (PFS)	Utilize radiography to estimate PFS of subjects with newly diagnosed, unresectable or recurrent/progressive ACP (with or without prior radiation therapy) treated with systemic tocilizumab.	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Feasibility Phase: Pathway Activation	To demonstrate evidence of WNT (Wingless-related integration site) in tumor tissue using immunohistochemistry and transcription array	Start of study to end of study, up to 5 years
Feasibility Phase: Pathway Activation	To demonstrate evidence of MAPK (mitogen activated protein kinases) in tumor tissue using immunohistochemistry and transcription arr	Start of study to end of study, up to 5 years
Feasibility Phase: Immunity	To demonstrate immune cell infiltration in tumor tissue using immunohistochemistry and flow cytometry	Start of study to end of study, up to 5 years
Feasibility Phase: Cytokines	To characterize cytokine signaling in tumor tissue and/or cyst fluid using enzyme-linked immunosorbent assay (ELISA)To characterize cytokine signaling in tumor tissue and/or cyst fluid using enzyme-linked immunosorbent assay (ELISA)	Start of study to end of study, up to 5 years
Feasibility Phase: Overall Response Rate (ORR)	Utilize radiography to estimate the overall response rate of subjects with newly diagnosed, unresectable or recurrent/progressive ACP (with or without prior radiation therapy) treated with systemic tocilizumab.	Start of study to end of study, or up to 5 years
Feasibility Phase: 1-Year Disease Stabilization	Utilize radiography to estimate the 1-year disease stabilization rate of subjects with newly diagnosed, unresectable or recurrent/progressive ACP (with or without prior radiation therapy) treated with systemic tocilizumab.	Start of study to 1 year post treatment

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Margaret Macy, MD, Children's Hospital Colorado

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2019
• Primary Completion (Actual): May 26, 2024
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: April 11, 2019
• First Submitted That Met QC Criteria: May 29, 2019
• First Posted (Actual): May 31, 2019

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Feasibility; Tocilizumab; Phase 0
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Craniopharyngioma; tocilizumab
• Other Study ID Numbers: 18-2143.cc; R03CA235200 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No