Patient case: 84-year-old male with glioblastoma; genetic feature: CDK6

Clinical trial: A Phase I Trial of High-Dose Ascorbate in Glioblastoma Multiforme

Summary: This is a phase 1 (first in man) study testing the safety of adding high dose ascorbate (vitamin C) to standard radiation and chemotherapy for initial treatment of glioblastoma multiforme (GBM).

Detailed description: This phase 1 study will test the safety of adding high dose ascorbate (vitamin C) to standard chemoradiation and, after the radiation is completed, during 6 cycles of temozolomide.
  Standard treatment for glioblastoma multiforme (GBM) involves surgery followed by radiation combined with temozolomide (a chemotherapy). After radiation, patients receive cycles of temozolomide (adjuvant chemotherapy)
  Participants will:
  -  receive high doses of intravenous (IV) ascorbate three times a week during chemoradiation
  -  receive high doses of intravenous (IV) ascorbate twice a week during adjuvant chemotherapy (after radiation)
  This is a phase 1 study will evaluate the side effects of adding this drug to the standard therapy. The dose given to a participant will be determined by how well other participants have tolerated the drug.

Eligibility: 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.
  -  Age ≥ 18 years
  -  ECOG performance status 0-2 (Karnofsky > 50%).
  -  A complete blood count and differential must be obtained within 21 days prior to the first dose of radiation, with adequate bone marrow functions as defined below:
  -  Absolute neutrophil count (ANC) ≥ 1500 cells per mm3
  -  Platelets ≥ 100,000 per mm3
  -  Hemoglobin ≥ 8 g/dL
  -  Serum blood chemistries within 21 days before the first day of radiation, as defined below:
  -  Creatinine ≤ 2.0 mg
  -  Total bilirubin ≤ 1.5 mg/dL
  -  ALT (Alanine Aminotransferase)≤ 3 times the institutional upper limit of normal
  -  AST (Aspartate Aminotransferase) ≤ 3 times the institutional upper limit of normal
  -  Tolerate one text dose (15g) of ascorbate
  -  Not pregnant
  -  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 unless approved by the study medical monitor, study sponsor, and the study principal investigator.
  -  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.
  -  Known HIV-positive individuals. High-dose ascorbate acid is a known CYP450 3A4 (an enzyme pathway) inducer, which results in lower serum levels of antiretroviral drugs

Relevance to patient case: not relevant