High-Dose Ascorbic Acid in Treating Patients with Newly Diagnosed Glioblastoma Multiforme Receiving Temozolomide and Undergoing Radiation Therapy

Status: Closed to Accrual

Description

This phase I trial studies the side effects and best dose of high-dose ascorbic acid in treating patients with newly diagnosed glioblastoma multiforme receiving temozolomide and undergoing radiation therapy. Ascorbic acid may kill tumor cells and may be an effective treatment for glioblastoma multiforme.

Eligibility Criteria

Inclusion Criteria

  • Patients must have newly diagnosed (i.e., within 5 weeks), histologically or cytologically confirmed glioblastoma multiforme
  • Diagnosis must be made by surgical biopsy or excision
  • Therapy must begin =< 5 weeks after surgery
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky > 50%)
  • Absolute neutrophil count (ANC) >= 1500 cells per mm^3
  • Platelets >= 100,000 per mm^3
  • Hemoglobin >= 8 g/dL
  • Creatinine =< 2.0 mg
  • Total bilirubin =< 1.5 mg/dL
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 times the institutional upper limit of normal
  • Tolerate one test dose (15 g) of ascorbate
  • Not pregnant; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; pregnancy tests will be obtained per physician discretion
  • Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

  • Recurrent high grade glioma
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide
  • Significant co-morbid central nervous system disease, including but not limited to, multiple sclerosis
  • Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide; high dose ascorbic acid may affect urine acidification and, as a result, may affect clearance rates of these drugs
  • Prior invasive malignancies (except non-melanomatous skin cancers and carcinoma in situ of the cervix or bladder) unless disease free for >= 5 years
  • Patients who have received prior chemotherapy (including Gliadel wafers) for the current glioma
  • Prior radiation therapy to the head or neck, which would result in overlap of radiation therapy fields
  • Patients may not be receiving any other investigational agents
  • 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 because ionizing radiation is a known teratogen, and temozolomide is a class D agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with temozolomide, breastfeeding should be discontinued if the mother is treated with temozolomide
  • Known human immunodeficiency virus (HIV)-positive individuals; high-dose ascorbate acid is a known cytochrome P450 3A4 (CYP450 3A4) inducer, which results in lower serum levels of antiretroviral drugs; a clinical trial designed to address these interaction issues is more appropriate than this phase 1 study

Locations & Contacts

See trial information on ClinicalTrials.gov for a list of participating sites.

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. Determine the safety and acute toxicity of high dose ascorbate (ascorbic acid) when administered as an adjuvant treatment during standard chemoradiation for glioblastoma multiforme (GBM).

SECONDARY OBJECTIVES:

I. Determine the overall survival and progression free survival of patients with newly diagnosed GBM treated with high dose ascorbate and standard chemoradiation.

II. Categorize and quantify adverse events in GBM subjects when treated with the combination of temozolomide, radiation and high-dose ascorbic acid compared to temozolomide and radiation alone.

OUTLINE: This is a dose-escalation study.

CHEMORADIATION: Patients receive ascorbic acid intravenously (IV) over 30-210 minutes three times per week beginning 1 week before chemoradiation. Patients also undergo radiation therapy 5 days per week for 5 weeks and receive concurrent temozolomide orally (PO) once daily (QD) for 5 weeks.

ADJUVANT THERAPY: Patients receive temozolomide PO QD on days 1-5 and ascorbic acid IV over 30-210 minutes twice weekly. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
University of Iowa / Holden Comprehensive Cancer Center

Principal Investigator
John M. Buatti

Trial IDs

Primary ID 201211713
Secondary IDs NCI-2013-00952
Clinicaltrials.gov ID NCT01752491