Imiquimod/Brain Tumor Initiating Cell (BTIC) Vaccine in Brain Stem Glioma

NCT01400672 | Terminated Phase 1 DMC

• 2 other identifiers: 2009LS1361004M81213
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot/feasibility study. The study design represents a modification of current standard of care for Diffuse Intrinsic Pontine Glioma (DIPG) (5580 cGY involved field radiation), with the final two doses of radiation given at intervals during the vaccination phase of treatment. Patients between the ages of 3 years and 25 years diagnosed with Diffuse Intrinsic Pontine Glioma (DIPG) will be allowed to participate in the trial. Study enrollment will occur after the completion of conformal radiation therapy to a dose of 5580 cGy and the post radiation therapy (RT) magnetic resonance imaging (MRI) shows no disease progression. Three patients with glioblastoma multiforme, aged 16 years and older, will be entered first to confirm vaccine safety before enrolling DIPG patients.

Conditions

Diffuse Intrinsic Pontine Glioma

Keywords

Diffuse intrinsic pontine glioma

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity

  Determined as Grade 3 or 4 toxicity observation after dosing with BTIC vaccination. Toxicity will be graded using the NCI's Common Terminology Criteria for Adverse Events (CTCAE 4.0) in terms of local, regional and systemic events.

  Within 24 hours of vaccination

Secondary Outcomes (2)

• Time to Tumor Progression

  Study entry through 24 months after treatment

• Drop-out rate

  24 hours, 48 hours and 1 week after each vaccination

Study Arms (1)

DIPG Patients Receiving Vaccine

EXPERIMENTAL

Patients with diffuse intrinsic pontine glioma (DIPG) receiving radiation therapy, Tumor Lysate Vaccine (dose of 4 x 10\^6 cells divided into 2 doses then every 4 weeks for up to 1 year) and Imiquimod (5% Aldara cream at a total dose of 12.5 mg) topically at each site prior to and 24 hours after vaccination.

Biological: Tumor Lysate Vaccine; Drug: Imiquimod; Radiation: Radiation therapy

Interventions

Tumor Lysate Vaccine BIOLOGICAL

Vaccination is injected intradermally every 2 weeks for 4 doses, then every 4 weeks for up to 1 year. Patients will receive 1 mg protein divided into 2 doses at two separate subinguinal sites.

DIPG Patients Receiving Vaccine

Imiquimod DRUG

Marketed as 5% Aldara cream topically applied; total of 12.5 mg divided between the two vaccination sites and reapplied at the vaccination sites 24 hours later.

Also known as: Aldara cream

DIPG Patients Receiving Vaccine

Radiation therapy RADIATION

Initial course of radiation therapy is given over 6-7 weeks, 5580 cGy. At the time of the 3rd vaccination, an additional 180 cGy fractions will be delivered in single doses in a novel effort to induce NKG2D ligand upregulation (thereby "sensitizing" residual tumor to lymphocyte attack). The total radiation dose for each patient will be 5760 cGy.

DIPG Patients Receiving Vaccine

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 16 years or older patients with histologically confirmed glioblastoma multiforme (GBM) World Health Organization (WHO) grade III-IV with recurrent or progressive disease after standard therapy (enrollment plan 1).
• Age 3 years and older patients with diffuse intrinsic pontine glioma (DIPG) diagnosed by magnetic resonance imaging (MRI). Completion of standard radiation therapy (not to exceed 5580 cGy) with a post radiation therapy (RT) MRI that shows no disease progression when compared with pre-RT MRI. All patients must be treated with Intensity Modulated Radiation Therapy (IMRT) or an equivalent conformal technique. Patients from an outside institution who are referred after the start of radiation therapy may complete initial radiation therapy at their home institution as long as dosage guidelines are met and the total dose does not exceed 5580 cGy at the time of study registration (enrollment plan 2 and 3).
• all patients regardless of diagnosis must be clinically stable and off or on low dose (no more than 0.1 mg/kg/day, maximum of 4 mg/day dexamethasone) corticosteroid for at least 1 week prior to study enrollment.

You may not qualify if:

• Pregnant or breast-feeding. Pregnancy testing will be performed on all menstruating females within 14 days prior to study enrollment.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
• Currently receiving any chemotherapy, investigational agents or registration on another therapy based trial or received chemotherapy with radiation therapy
• History of immune system abnormalities such as hyperimmunity (e.g., autoimmune diseases) and hypoimmunity (e.g., myelodysplastic disorders, marrow failures, AIDS, ongoing pregnancy, transplant immunosuppression)
• Any isolated laboratory abnormality suggestive of a serious autoimmune disease
• Any conditions that could potentially alter immune function (AIDS, multiple sclerosis, diabetes, renal failure)
• Receiving ongoing treatment with immunosuppressive drugs, excluding those patients requiring dexamethasone for treatment of tumor-related edema

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma

Interventions

Imiquimod; Radiotherapy

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Therapeutics

Study Officials

• Christopher Moertel, M.D.

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2011
• First Posted: July 22, 2011
• Study Start: July 17, 2012
• Primary Completion: March 7, 2016
• Study Completion: October 8, 2018
• Last Updated: March 18, 2020

Record last verified: 2020-03

Locations

US (1)