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High-Dose Ascorbic Acid, Temozolomide, and Radiation Therapy in Treating Patients with Glioblastoma

Trial Status: Active

This phase II trial studies how well high-dose ascorbic acid, temozolomide, and radiation therapy work in treating patients with glioblastoma. Dietary supplements, such as ascorbic acid, may improve the tolerability of chemotherapy regimens. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving high-dose ascorbic acid, temozolomide, and radiation therapy may work better in treating patients with glioblastoma.

Inclusion Criteria

  • Patients must have newly diagnosed (i.e., within 5 weeks), histologically or cytologically confirmed glioblastoma multiforme
  • Diagnosis must be made by biopsy or excision
  • Therapy must begin =< 5 weeks after surgery or biopsy
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky > 50%)
  • A complete blood count and differential must be obtained within 21 days prior to radiation fraction 1
  • 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) =< 3 times the institutional upper limit of normal
  • 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; pregnancy tests will be obtained per institutional policies
  • Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

  • Recurrent high grade glioma
  • G6PD (glucose-6-phosphate dehydrogenase) deficiency
  • Patients actively receiving insulin are excluded unless approved by the investigational new drug (IND) medical monitor, IND sponsor, and the study principal investigator (PI)
  • Patients requiring daily finger-stick blood glucose measurements unless approved by the IND medical monitor, IND sponsor, and the study PI
  • 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 warfarin and cannot have a drug substitution or who decline the drug substitution
  • 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 resulting in overlap of radiotherapy (RT) fields
  • Patients may not be receiving any other investigational agents with the intent to treat the disease (imaging agents are acceptable)
  • 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; 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 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 2 study

Iowa

Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: ACTIVE
Contact: Bryan G. Allen
Phone: 319-353-8836

PRIMARY OBJECTIVES:

I. Determine the overall survival of patients with newly diagnosed glioblastoma multiforme (GBM) treated with high dose ascorbic acid (ascorbate) and standard radiation combined with chemotherapy.

SECONDARY OBJECTIVES:

I. Determine the progression free survival of patients with newly diagnosed GBM treated with high dose ascorbate and standard radiation combined with chemotherapy.

II. Determine tumor response using the criteria defined by MacDonald et al.

III. 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.

TERTIARY OBJECTIVES:

I. Determine health-related quality of life outcomes (HRQOL) using the validated European Organization for Research and Treatment of Cancer (EORTC) questionnaires quality of life questionnaire (QLQ)- core (C)30 and BN-20.

II. Compare health-related quality of life outcomes to the findings of Stupp et al in the pivotal EORTC study defining concomitant therapy for GBM.

OUTLINE:

Patients undergo radiation therapy 5 days per week. Patients also receive temozolomide orally (PO) once daily (QD) and ascorbic acid intravenously (IV) over 150 minutes 3 times per week during radiation therapy.

POST-RADIATION THERAPY: Patients receive ascorbic acid IV over 150 minutes twice weekly.

ADJUVANT THERAPY: Patients receive temozolomide PO QD on days 1-5 and ascorbic acid IV over 150 minutes twice weekly for 4 weeks for a total of 8 infusions. 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 at 30 days and then every 3 months.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
University of Iowa / Holden Comprehensive Cancer Center

Principal Investigator
Bryan G. Allen

  • Primary ID 201504786
  • Secondary IDs NCI-2017-00716
  • Clinicaltrials.gov ID NCT02344355