Clinical trial NCT03970226: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Adamantinomatous Craniopharyngioma
Keywords: Phase 0
Feasibility
Tocilizumab
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: National Institutes of Health (NIH)
First posted: 2019-05-31
Enrollment: 9
Sex: ALL
Minimum age (years): 2
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Phase 0: Presence of Tocilizumab and Metabolites
timeFrame: Within 4 to 8 hours of administration of tocilizumab
measure: Feasibility Phase: Toxicity Profile
timeFrame: Start of study to end of study, up to 5 years
Secondary outcomes:
measure: Phase 0: IL6 and Inflammatory Cytokines
timeFrame: Within 4 to 8 hours of administration of tocilizumab
measure: Feasibility Phase: Progression Free Survival (PFS)
timeFrame: 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
measure: Feasibility Phase: Pathway Activation
timeFrame: Start of study to end of study, up to 5 years
measure: Feasibility Phase: Pathway Activation
timeFrame: Start of study to end of study, up to 5 years
measure: Feasibility Phase: Immunity
timeFrame: Start of study to end of study, up to 5 years
measure: Feasibility Phase: Cytokines
timeFrame: Start of study to end of study, up to 5 years
measure: Feasibility Phase: Overall Response Rate (ORR)
timeFrame: Start of study to end of study, or up to 5 years
measure: Feasibility Phase: 1-Year Disease Stabilization
timeFrame: Start of study to 1 year post treatment
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
Study officials:
affiliation: Children's Hospital Colorado
name: Margaret Macy, MD
role: PRINCIPAL_INVESTIGATOR
References: