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

NCT01151670 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: IRB00014528NCI-2009-01452CCCWFU 97409
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Brain Neoplasms, Malignant; Brain Neoplasms, Benign; Malignant Meningioma; Glioblastoma Multiforme; Anaplastic Astrocytoma

Keywords

radiation therapy; cognitive dysfunction; brain tumor; memory problems; short term memory loss

Outcome Measures

Primary Outcomes (1)

• Best tolerated dose of 2 different doses of orally administered pioglitazone

  From first dose to 1 day after last dose of drug

Secondary Outcomes (2)

• Toxicities associated with both dose levels

  From first dose to 1 day after last dose of drug

• 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.

  From first dose to 1 day after last dose of drug

Study Arms (2)

Arm I

EXPERIMENTAL

Pioglitazone 22.5 mg once daily by mouth

Drug: pioglitazone

Arm 2

EXPERIMENTAL

Pioglitazone 45 mg once daily by mouth

Drug: Pioglitazone

Interventions

Pioglitazone DRUG

Pioglitazone 22.5 mg daily before, during and after radiation therapy.

Also known as: Actos

Arm I

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead

Study Sites (1)

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Meningioma; Glioblastoma; Astrocytoma; Cognitive Dysfunction; Memory Disorders

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Michael Chan

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2010
• First Posted: June 28, 2010
• Study Start: August 1, 2010
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: August 1, 2018

Record last verified: 2018-07

Locations

US (1)