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| ID | Type | Description | Link |
|---|---|---|---|
| R03CA235200 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
| National Institutes of Health (NIH) | NIH |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tocilizumab Administration: Phase 0 | Experimental | In Phase 0, patients will receive one dose of tocilizumab prior to surgery. |
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| Tocilizumab Administration: Feasibility Phase | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tocilizumab | Drug | Phase 0: One dose of tocilizumab prior to surgery Feasibility phase: Tocilizumab administered every 2 weeks for up to 13 cycles (approximately 1 year). |
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| 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 |
| 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) |
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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:
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:
Adequate renal function defined as:
Adequate liver function defined as:
Subjects must meet one of the following performance scores:
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:
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
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| Name | Affiliation | Role |
|---|---|---|
| Margaret Macy, MD | Children's Hospital Colorado | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital Colorado | Aurora | Colorado | 80045 | United States |
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| ID | Term |
|---|---|
| D003397 | Craniopharyngioma |
| ID | Term |
|---|---|
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C502936 | tocilizumab |
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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.
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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 |
| D009380 | Neoplasms, Nerve Tissue |