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

This study is currently recruiting participants.
Verified December 2013 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT01400672
First received: July 19, 2011
Last updated: December 18, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Diffuse Intrinsic Pontine Glioma
Glioblastoma Multiforme
Adult Glioblastoma
Biological: Tumor Lysate Vaccine
Drug: Imiquimod
Radiation: Radiation therapy
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Imiquimod/BTIC Lysate-Based Vaccine Immunotherapy for Diffuse Intrinsic Pontine Glioma in Children and Young Adults

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Dose-limiting toxicity [ Time Frame: Within 24 hours of vaccination ] [ Designated as safety issue: Yes ]
    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.

  • Drop-out rate [ Time Frame: 24 hours, 48 hours and 1 week after each vaccination ] [ Designated as safety issue: Yes ]
    Treatment feasibility will be based on the drop-out rate in absence of disease progression. Information will be presented in a tabular and descriptive manner


Secondary Outcome Measures:
  • Time to Tumor Progression [ Time Frame: Study entry through 24 months after treatment ] [ Designated as safety issue: No ]

    Imaging will include MRI, SPECT/MRI and perfusion MRI. FDG-PET imaging may be also be used Response criteria: Complete responses (CR) are those in which there is a disappearance of all enhancing tumor or tumor mass on consecutive MRI scans. Patients must be off steroids, and neurologically stable or improved.

    Partial responses (PR) are those in which there is a ≥ 50% reduction in the size of the enhancing tumor or tumor mass on consecutive MRI scans. In addition, the patient must be neurologically stable.



Estimated Enrollment: 20
Study Start Date: July 2012
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DIPG Patients Receiving Vaccine
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
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.
Drug: Imiquimod
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.
Other Name: Aldara cream
Radiation: Radiation therapy
Initial course of radiation therapy is given over 6-7 weeks, 5580 cGy. Additional 180 cGy fractions will be delivered as a single dose on days of 1st and 3rd vaccinations and given according to standard of care at University of Minnesota Medical Center. Total radiation dose will be 5940 cGy.

Detailed Description:

Vaccine will be produced by the University Of Minnesota Molecular and Cellular Therapeutics Facility using the established brain tumor initiating cell (BTIC) cell line GBM-6 as the antigen source. Vaccine administration will begin at four weeks (week 10) following completion of radiation therapy and will be given every two weeks for four doses. At the time of the 1st and 3rd vaccinations, 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 5940 cGy. Subsequent vaccinations will be given every four weeks and will continue to a maximum of one year from study enrollment, by which time median survival will have passed based on historical data. Imaging will be obtained at study entry (post radiation therapy) and every eight weeks thereafter to eighteen months, after which time the interval between imaging follow-up episodes will be determined by the patient's clinical status. Imaging will include MRI of the brain using our current institutional brain tumor imaging protocol. Imaging will also include SPECT/MRI and perfusion MRI. FDG-PET imaging may be used in certain cases to differentiate tumor necrosis from progression.

  Eligibility

Ages Eligible for Study:   3 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria - GBM patients only (enrollment plan 1):

  • Histologically confirmed glioblastoma multiforme (GBM) World Health Organization (WHO) grade III-IV with recurrent or progressive disease after standard therapy
  • Age 16 years or older

Inclusion Criteria - DIPG patients only (enrollment plan 2 and 3):

  • Diagnosis of diffuse intrinsic pontine glioma (DIPG) by magnetic resonance imaging (MRI). Because the safety of biopsy of DIPG has not been firmly established, biopsy will not be required for study enrollment.
  • 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. The clinical target volume will be defined as the gross tumor volume (full extent of tumor visible on MRI) plus 1 cm margin. 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.
  • Able to begin vaccination 4 weeks (+ or - 1 week) of completion of standard radiation therapy
  • Age 3 years and older Inclusion Criteria - all patients regardless of diagnosis
  • 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
  • Lansky (0-15 years) or Karnofsky (16 years or older) performance score of ≥ 60
  • Adequate organ function within 14 days of study registration including the following:

    • Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥ 1.0 x 10^9/L, platelets ≥ 100 x 10^9/L; Hemoglobin ≥ 8 g/dL
    • Hepatic: - Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age and SGPT (ALT) ≤ 2.5 x upper limit of normal (ULN) for age
    • Renal: Normal serum creatinine for age or creatinine clearance >60 ml/min/1.73 m^2.
  • Sexually active females of child bearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of the vaccination period. Sexually active males must agree to use barrier contraceptive for the duration of the vaccination period.
  • Voluntary written informed consent must be obtained from all patients (if of assent age) and their parents or legal guardians before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Exclusion Criteria - all patients:

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01400672

Contacts
Contact: Christopher Moertel, MD 612-626-2778 moert001@umn.edu
Contact: Tambra Dahlheimer, RN 612 626 2629 tdahlheimer@umphysicians.umn.edu

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Christopher Moertel, M.D.    612-626-2778    moert001@umn.edu   
Principal Investigator: Christopher Moertel, M.D.         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Christopher Moertel, M.D. Masonic Cancer Center, University of Minnesota
  More Information

No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT01400672     History of Changes
Other Study ID Numbers: 2009LS136, 1004M81213
Study First Received: July 19, 2011
Last Updated: December 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
Diffuse intrinsic pontine glioma
glioblastoma multiforme
adult glioblastoma

Additional relevant MeSH terms:
Glioblastoma
Glioma
Pontine Glioma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Imiquimod
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Interferon Inducers

ClinicalTrials.gov processed this record on April 17, 2014