Clinical Trials /

Tocilizumab in Children With ACP

NCT03970226

Description:

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, we will submit this study to COMIRB to review and approve opening the second phase of the study (feasibility phase). During this phase patients will be administered tocilizumab every two weeks for up to 26 cycles (approximately 2 years). Patients will be followed for up to 5 years in the feasibility phase.

Related Conditions:
  • Craniopharyngioma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 18-2143.cc
  • SECONDARY ID: 1R03CA235200-01
  • SECONDARY ID: P30CA046934
  • NCT ID: NCT03970226

Conditions

  • Adamantinomatous Craniopharyngioma

Interventions

DrugSynonymsArms
TocilizumabTocilizumab Administration: Phase 0 and Feasibility Phase

Purpose

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, we will submit this study to COMIRB to review and approve opening the second phase of the study (feasibility phase). During this phase patients will be administered tocilizumab every two weeks for up to 26 cycles (approximately 2 years). Patients will be followed for up to 5 years in the feasibility phase.

Trial Arms

NameTypeDescriptionInterventions
Tocilizumab Administration: Phase 0 and Feasibility PhaseExperimentalIn 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 26 cycles (approximately 2 years). Patients will be followed for up to 5 years.
  • Tocilizumab

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:

               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:

          -  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 reaccumulation of the cyst following one or more cyst
                  aspirations.

          -  Newly diagnosed, histologically confirmed ACP with unresectable residual 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

             a. Adequate bone marrow function defined as:

          -  Platelet count ≥100,000/μl (transfusion independent)

          -  Absolute neutrophil count (ANC) ≥2,000/μl b. 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 c. Adequate liver function defined as:

          -  SGOT (AST) and SGPT (ALT) <1.5x ULN for age

          -  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

          -  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:

               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.

          -  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
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:2 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 0: Presence of Tocilizumab and Metabolites
Time Frame:Within 4 to 8 hours of administration of tocilizumab
Safety Issue:
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.

Secondary Outcome Measures

Measure:Phase 0: IL6 and Inflammatory Cytokines
Time Frame:Within 4 to 8 hours of administration of tocilizumab
Safety Issue:
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
Measure:Feasibility Phase: Progression Free Survival (PFS)
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
Safety Issue:
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.
Measure:Feasibility Phase: Toxicity Profile
Time Frame:Start of study to end of study, up to 5 years
Safety Issue:
Description:To define toxicities of tocilizumab therapy using CTCAE version 5.
Measure:Feasibility Phase: Pathway Activation
Time Frame:Start of study to end of study, up to 5 years
Safety Issue:
Description:To demonstrate evidence of WNT (Wingless-related integration site) in tumor tissue using immunohistochemistry and transcription array
Measure:Feasibility Phase: Pathway Activation
Time Frame:Start of study to end of study, up to 5 years
Safety Issue:
Description:To demonstrate evidence of MAPK (mitogen activated protein kinases) in tumor tissue using immunohistochemistry and transcription arr
Measure:Feasibility Phase: Immunity
Time Frame:Start of study to end of study, up to 5 years
Safety Issue:
Description:To demonstrate immune cell infiltration in tumor tissue using immunohistochemistry and flow cytometry
Measure:Feasibility Phase: Cytokines
Time Frame:Start of study to end of study, up to 5 years
Safety Issue:
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)

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Colorado, Denver

Trial Keywords

  • Phase 0
  • Feasibility
  • Tocilizumab

Last Updated