Tocilizumab in Children With ACP

Early Phase 1

Recruiting

• Conditions: Adamantinomatous Craniopharyngioma
• Interventions: Drug: Tocilizumab

• Registration Number: NCT03970226
• Lead Sponsor: University of Colorado, Denver

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-04-11
• Study First Submitted QC: 2019-05-29
• Study First Posted: 2019-05-31
• Study Start: 2019-09-16
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-27
• Last Update Posted: 2025-01-28
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 27

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tocilizumab Administration: Phase 0	Tocilizumab	In Phase 0, patients will receive one dose of tocilizumab prior to surgery.
Tocilizumab Administration: Feasibility Phase	Tocilizumab	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.

Primary Outcome Measures

Name	Time	Method
Feasibility Phase: Toxicity Profile	Start of study to end of study, up to 5 years	To define toxicities of tocilizumab therapy using CTCAE version 5.
Phase 0: Presence of Tocilizumab and Metabolites	Within 4 to 8 hours of administration of tocilizumab	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.

Secondary Outcome Measures

Name	Time	Method
Feasibility Phase: Overall Response Rate (ORR)	Start of study to end of study, or up to 5 years	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.
Feasibility Phase: Progression Free Survival (PFS)	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	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.
Feasibility Phase: Pathway Activation	Start of study to end of study, up to 5 years	To demonstrate evidence of MAPK (mitogen activated protein kinases) in tumor tissue using immunohistochemistry and transcription arr
Phase 0: IL6 and Inflammatory Cytokines	Within 4 to 8 hours of administration of tocilizumab	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
Feasibility Phase: Immunity	Start of study to end of study, up to 5 years	To demonstrate immune cell infiltration in tumor tissue using immunohistochemistry and flow cytometry
Feasibility Phase: Cytokines	Start of study to end of study, up to 5 years	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)
Feasibility Phase: 1-Year Disease Stabilization	Start of study to 1 year post treatment	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.

Trial Locations

Locations (1)

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States