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Tocilizumab in Children With ACP

Primary Purpose

Adamantinomatous Craniopharyngioma

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Tocilizumab
Sponsored by
University of Colorado, Denver
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adamantinomatous Craniopharyngioma focused on measuring Phase 0, Feasibility, Tocilizumab

Eligibility Criteria

2 Years - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Children's Hospital ColoradoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Tocilizumab Administration: Phase 0

Tocilizumab Administration: Feasibility Phase

Arm Description

In Phase 0, patients will receive one dose of tocilizumab prior to surgery.

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.

Outcomes

Primary Outcome Measures

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.
Feasibility Phase: Toxicity Profile
To define toxicities of tocilizumab therapy using CTCAE version 5.

Secondary Outcome Measures

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
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.
Feasibility Phase: Pathway Activation
To demonstrate evidence of WNT (Wingless-related integration site) in tumor tissue using immunohistochemistry and transcription array
Feasibility Phase: Pathway Activation
To demonstrate evidence of MAPK (mitogen activated protein kinases) in tumor tissue using immunohistochemistry and transcription arr
Feasibility Phase: Immunity
To demonstrate immune cell infiltration in tumor tissue using immunohistochemistry and flow cytometry
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)
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.
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.

Full Information

First Posted
April 11, 2019
Last Updated
May 18, 2023
Sponsor
University of Colorado, Denver
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03970226
Brief Title
Tocilizumab in Children With ACP
Official Title
A Phase 0/Feasibility Trial of Tocilizumab in Children and Adolescents With Newly- Diagnosed or Recurrent/Progressive Adamantinomatous Craniopharyngioma
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 6, 2019 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adamantinomatous Craniopharyngioma
Keywords
Phase 0, Feasibility, Tocilizumab

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Phase 0 to open first and if outcomes are favorable showing drug penetration then the Feasibility Phase will open. Both arms will be open concurrently.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
27 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Tocilizumab Administration: Phase 0
Arm Type
Experimental
Arm Description
In Phase 0, patients will receive one dose of tocilizumab prior to surgery.
Arm Title
Tocilizumab Administration: Feasibility Phase
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Other Intervention Name(s)
Actemra
Intervention Description
Phase 0: One dose of tocilizumab prior to surgery Feasibility phase: Tocilizumab administered every 2 weeks for up to 13 cycles (approximately 1 year).
Primary Outcome Measure Information:
Title
Phase 0: Presence of Tocilizumab and Metabolites
Description
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.
Time Frame
Within 4 to 8 hours of administration of tocilizumab
Title
Feasibility Phase: Toxicity Profile
Description
To define toxicities of tocilizumab therapy using CTCAE version 5.
Time Frame
Start of study to end of study, up to 5 years
Secondary Outcome Measure Information:
Title
Phase 0: IL6 and Inflammatory Cytokines
Description
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
Time Frame
Within 4 to 8 hours of administration of tocilizumab
Title
Feasibility Phase: Progression Free Survival (PFS)
Description
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.
Time Frame
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
Title
Feasibility Phase: Pathway Activation
Description
To demonstrate evidence of WNT (Wingless-related integration site) in tumor tissue using immunohistochemistry and transcription array
Time Frame
Start of study to end of study, up to 5 years
Title
Feasibility Phase: Pathway Activation
Description
To demonstrate evidence of MAPK (mitogen activated protein kinases) in tumor tissue using immunohistochemistry and transcription arr
Time Frame
Start of study to end of study, up to 5 years
Title
Feasibility Phase: Immunity
Description
To demonstrate immune cell infiltration in tumor tissue using immunohistochemistry and flow cytometry
Time Frame
Start of study to end of study, up to 5 years
Title
Feasibility Phase: Cytokines
Description
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)
Time Frame
Start of study to end of study, up to 5 years
Title
Feasibility Phase: Overall Response Rate (ORR)
Description
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.
Time Frame
Start of study to end of study, or up to 5 years
Title
Feasibility Phase: 1-Year Disease Stabilization
Description
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.
Time Frame
Start of study to 1 year post treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Phase 0 Eligibility: 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 Must meet one of the following criteria: Presumed craniopharyngioma based on imaging features and best judgement of treating medical team (if newly diagnosed) Previous histologically confirmed ACP that has progressed or recurred at the time of enrollment Feasibility Eligibility: Must meet one of the following criteria: Recurrent or progressive* ACP treated with surgery alone without radiation 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. Newly diagnosed, by histology or imaging ACP with unresectable residual cystic and/or solid disease that is measurable in 2 dimensions 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: Age: ≥ 2 years and < 21 years Subjects may have received prior tocilizumab or other IL6 or IL6R inhibitor Organ Function Requirements Adequate bone marrow function defined as: Platelet count ≥100,000/μl (transfusion independent) Absolute neutrophil count (ANC) ≥1500/μl 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 Adequate liver function defined as: SGOT (AST) and SGPT (ALT) <1.5x ULN for age Subjects must meet one of the following performance scores: ECOG performance status scores of 0, 1, or 2; Karnofsky score of ≥60 for patients > 16 years of age; or Lansky score of ≥60 for patients ≤16 years of age 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. Informed consent and assent obtained as appropriate. Exclusion Criteria Pregnant or breastfeeding Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection (including active tuberculosis) symptomatic congestive heart failure unstable angina pectoris cardiac arrhythmia psychiatric illness/social situations that would limit compliance with study requirements are not eligible. Known hypersensitivity or history of anaphylaxis to tocilizumab Received any live vaccinations within 3 months prior to start of therapy Evidence of metastatic disease or other cancer Inability to return for follow up visits or obtain required follow-up studies to assess toxicity of therapy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ashley Mettetal
Phone
720-777-5305
Email
Ashley.Mettetal@childrenscolorado.org
First Name & Middle Initial & Last Name or Official Title & Degree
Shandi Watts
Phone
7207773214
Email
shandi.watts@childrenscolorado.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kathleen Dorris, MD
Organizational Affiliation
University of Colorado, Denver
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kathleen Dorris, MD
Email
kathleen.dorris@childrenscolorado.org

12. IPD Sharing Statement

Plan to Share IPD
No

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Tocilizumab in Children With ACP

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