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Phase I Study to Determine Safety of Pioglitazone Combined With Radiation Therapy in Subjects With Brain Tumors

Phase 1
18 Years
Open (Enrolling)
Adult Anaplastic Astrocytoma, Adult Anaplastic Ependymoma, Adult Anaplastic Meningioma, Adult Anaplastic Oligodendroglioma, Adult Brain Stem Glioma, Adult Choroid Plexus Tumor, Adult Craniopharyngioma, Adult Diffuse Astrocytoma, Adult Ependymoblastoma, Adult Ependymoma, Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Adult Grade I Meningioma, Adult Grade II Meningioma, Adult Medulloblastoma, Adult Meningeal Hemangiopericytoma, Adult Mixed Glioma, Adult Myxopapillary Ependymoma, Adult Oligodendroglioma, Adult Papillary Meningioma, Adult Pilocytic Astrocytoma, Adult Pineal Gland Astrocytoma, Adult Pineoblastoma, Adult Pineocytoma, Adult Subependymal Giant Cell Astrocytoma, Adult Subependymoma, Adult Supratentorial Primitive Neuroectodermal Tumor (PNET), Meningeal Melanocytoma, Nonmalignant Neoplasm, Recurrent Adult Brain Tumor, Tumors Metastatic to Brain

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Trial Information

Phase I Study to Determine Safety of Pioglitazone Combined With Radiation Therapy in Subjects With Brain Tumors


I. To evaluate the tolerability and toxicity associated with two different dose regimens of
pioglitazone (pioglitazone hydrochloride) administered orally as a cytoprotective agent
against radiation-induced brain injury.


I. To evaluate the effect of pioglitazone on glycemic levels and hemoglobin A1c values when
pioglitazone is used as a cytoprotective agent concurrent with radiotherapy in normoglycemic

OUTLINE: This is a dose escalation study of pioglitazone hydrochloride.

Patients undergo fractionated external beam radiotherapy. Beginning one day before
radiotherapy, patients receive pioglitazone hydrochloride orally (PO) 5 days per week,
continuing throughout radiotherapy and then for 6 months after completion of radiotherapy.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed primary brain tumors
either benign or malignant), or histologically or cytologically confirmed primary
cancer with brain tumors that are consistent with brain metastases upon imaging, of
the following types:

- Group 1: Malignant brain tumors: glioblastoma multiforme, anaplastic gliomas,
brain metastases, and other malignant brain tumors

- Group 2: Low grade brain tumors: low grade gliomas, meningiomas (do not need
biopsy for radiographically diagnosed meningiomas), and other low grade brain
tumors including all other benign brain tumors

- All stages and grades of brain tumors are eligible

- Patients must have agreed to be treated with fractionated, external beam radiation
treatment (EBRT) with either curative or palliative intent (the length of the
radiation course must at least be ten fractions)

- Patients must have agreed to have computed tomography (CT) and magnetic resonance
(MR) imaging for purposes of radiation treatment planning, radiation treatment
monitoring, and/or radiation treatment evaluation

- Patients must have measurable disease using Magnetic Resonance Imaging

- Prior and concurrent therapies (cytotoxic, surgery, and radiation) are acceptable

- Use of steroids is acceptable when indicated

- Patients must be able to understand and willingly give informed written consent to

- Women of childbearing potential must have a serum pregnancy test

- Patients must have a life expectancy of greater than 3 months

- Patients must be willing to comply with an oral treatment regimen and be able to
swallow oral study tablets

- Patients must have complete blood count, liver and kidney function panel within 2
weeks prior to registration

Exclusion Criteria:

- History of allergic reactions to pioglitazone or any other member of the
thiazolidinedione family

- Current diagnosis of diabetes as defined by fasting blood sugar > 125, treatment with
anti-diabetic medications (with the exception for insulin taken as a result of
steroid induced hyperglycemia), or history of diabetes

- Patients who have New York Heart Association (NYHA) class III or IV heart failure

- Patients who have elevated transaminases (aspartate aminotransferase [AST[ or alanine
aminotransferase [ALT] > 2.5 times normal limit)

- Patients who have significantly impaired renal function (creatinine >= 1.5)

- Patients who are significantly anemic (hematocrit < 33% in men, or < 30% in women)

- Patients who have symptomatic edema (>= grade 2)

- Patients who are on medications that have been shown to have a drug interaction with
pioglitazone: atorvastatin (doses > 80 mg/day), systemic anti-fungals, medications
with significant cytochrome P450 3A4 (CYP 3A4) inhibiting properties

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac,
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant women will be excluded from this study because Pioglitazone is classified as
a pregnancy category C dug because it has been shown to cause toxicity to fetuses in
animals, but the effect is not well characterized in humans

- Patients with psychiatric or social illnesses that may impair compliance with the
trial requirements are to be excluded

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Outcome Measure:

Tolerability and toxicity, measured by incidence of dose limiting toxicities (DLT)

Outcome Description:

A DLT is defined as: 1) Common Toxicity Criteria (CTC) 3.0 Grade III weight gain, 2) Measurement and Grading of Peripheral Extremity Edema Scale Grade III edema, 3) CTC 3.0 Grade III hypoglycemia and 4) New York Heart Association (NYHA) Classification of Heart Failure Grade III symptoms of heart failure. Toxicity rates and exact 95% confidence intervals will be calculated separately for each dose level.

Outcome Time Frame:

Up to 30 days after the last treatment of radiotherapy

Safety Issue:


Principal Investigator

Michael Chan

Investigator Role:

Principal Investigator

Investigator Affiliation:

Comprehensive Cancer Center of Wake Forest University


United States: Institutional Review Board

Study ID:

CCCWFU 97409



Start Date:

September 2010

Completion Date:

Related Keywords:

  • Adult Anaplastic Astrocytoma
  • Adult Anaplastic Ependymoma
  • Adult Anaplastic Meningioma
  • Adult Anaplastic Oligodendroglioma
  • Adult Brain Stem Glioma
  • Adult Choroid Plexus Tumor
  • Adult Craniopharyngioma
  • Adult Diffuse Astrocytoma
  • Adult Ependymoblastoma
  • Adult Ependymoma
  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Adult Grade I Meningioma
  • Adult Grade II Meningioma
  • Adult Medulloblastoma
  • Adult Meningeal Hemangiopericytoma
  • Adult Mixed Glioma
  • Adult Myxopapillary Ependymoma
  • Adult Oligodendroglioma
  • Adult Papillary Meningioma
  • Adult Pilocytic Astrocytoma
  • Adult Pineal Gland Astrocytoma
  • Adult Pineoblastoma
  • Adult Pineocytoma
  • Adult Subependymal Giant Cell Astrocytoma
  • Adult Subependymoma
  • Adult Supratentorial Primitive Neuroectodermal Tumor (PNET)
  • Meningeal Melanocytoma
  • Nonmalignant Neoplasm
  • Recurrent Adult Brain Tumor
  • Tumors Metastatic to Brain
  • Astrocytoma
  • Brain Neoplasms
  • Neoplasms
  • Craniopharyngioma
  • Adamantinoma
  • Ependymoma
  • Glioblastoma
  • Glioma
  • Hemangiopericytoma
  • Medulloblastoma
  • Meningioma
  • Oligodendroglioma
  • Pinealoma
  • Choroid Plexus Neoplasms
  • Neuroectodermal Tumors
  • Neuroectodermal Tumors, Primitive
  • Glioma, Subependymal
  • Gliosarcoma



Wake Forest University Health SciencesWinston-Salem, North Carolina  27157