Pioglitazone Hydrochloride in Preventing Radiation-Induced Cognitive Dysfunction in Treating Patients With Brain Tumors

Wake Forest University (WFU)

Status and phase

Completed

Phase 1

Conditions

Glioblastoma Multiforme

Malignant Meningioma

Brain Neoplasms, Benign

Anaplastic Astrocytoma

Brain Neoplasms, Malignant

Treatments

Drug: pioglitazone

Drug: Pioglitazone

Study type

Interventional

Funder types

Other

Identifiers

NCT01151670

CCCWFU 97409 (Other Identifier)

IRB00014528

NCI-2009-01452 (Registry Identifier)

Details and patient eligibility

About

RATIONALE: Pioglitazone hydrochloride may be effective treatment for cognitive dysfunction caused by radiation therapy.

PURPOSE: This phase I trial is studying the side effects and best dose of pioglitazone hydrochloride in preventing radiation-induced cognitive dysfunction in treating patients with brain tumors.

Full description

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVE:

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 patients.

OUTLINE: Patients undergo fractionated external beam radiotherapy, 3-D conformal radiotherapy, or intensity-modulated radiotherapy. Patients receive oral pioglitazone hydrochloride once daily before for 1 week prior to brain irradiation, during and and continuing for 6 months after completion of radiation radiotherapy. After completion of study treatment, patients are followed periodically.

Enrollment

18 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients must have histologically or cytologically confirmed brain tumors of the following types: Group 1: malignant brain tumors (glioblastoma multiforme, anaplastic gliomas, brain metastases, and other malignant brain tumors); or Group 2: low grade brain tumors (low grade gliomas, meningiomas, and other low grade brain tumors)
All stages and grades of brain tumors are eligible
Patients must have an ECOG performance status of 0-2
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 CT and MR imaging for purposes of radiation treatment planning, radiation treatment monitoring, and/or radiation treatment evaluation
Patients must have measurable disease and/or relevant anatomic features using Magnetic Resonance Imaging
Prior 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 participate
Women of childbearing potential must not be pregnant or nursing and must use medically appropriate contraception if sexually active
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

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, or history of diabetes
Patients who take insulin
Patients who have NYHA class III or IV heart failure
Patients who have elevated transaminases (AST or 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 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 are excluded from this study if their pregnancy precludes radiation treatment because ionizing radiation used in radiation treatment is an agent with known potential for teratogenic or abortifacient effects
Patients with psychiatric or social illnesses that may impair compliance with the trial requirements