Clinical trial NCT02344355: A Phase 2 Trial of High-Dose Ascorbate in Glioblastoma Multiforme
Official title: Pharmacological Ascorbate Combined With Radiation and Temozolomide in Glioblastoma Multiforme: A Phase 2 Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Glioblastoma Multiforme
Keywords: Ascorbic Acid
temozolomide
radiation
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: Holden Comprehensive Cancer Center
name: National Cancer Institute (NCI)
name: Gateway for Cancer Research
First posted: 2015-01-22
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This clinical trial evaluates adding high-dose ascorbate (vitamin C) to standard of care treatment of glioblastoma multiforme (a type of brain tumor) in adults. All subjects will receive high-dose ascorbate in addition to the standard treatment.

Detailed description: Standard treatment for glioblastoma multiforme (GBM) involves maximum safe surgical resection followed by radiation combined with temozolomide (a chemotherapy pill you take by mouth). After radiation, patients receive additional cycles of temozolomide (adjuvant chemotherapy).

Participants will:

* receive high doses of intravenous (IV) ascorbate three times a week during the combined radiation and chemotherapy phase
* receive high doses of intravenous (IV) ascorbate twice a week during adjuvant chemotherapy (after radiation)
* complete health-related quality of life questionnaires pre-radiation, 4 weeks into radiation, 4 weeks after radiation, and then every 3 months. In addition, patients will complete neurocognitive testing pre-radiation, 4 weeks into radiation, 4 weeks after radiation, and approximately 9 months after initiating radiation therapy.

The adjuvant chemotherapy portion of this study lasts for 6 months. After that is completed, participants will go back to standard therapy for their cancer. Participants will continue to have life-long follow-up for this study.

Eligibility criteria: Inclusion Criteria:

* Ability to understand and willingness to sign informed consent (power of attorney and/or legally authorized representatives cannot sign on behalf of the patient)
* 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 or biopsy
* Age ≥ 18 years
* ECOG performance status 0-2. (KPS \> 50)
* Absolute neutrophil count (ANC) ≥ 1500 cells per mm3
* Platelets ≥ 100,000 per mm3
* Hemoglobin ≥ 8 g/dL
* Creatinine ≤ 2.0 mg
* Total bilirubin ≤ 1.5 mg/dL
* ALT ≤ 3 times the institutional upper limit of normal
* AST ≤ 3 times the institutional upper limit of normal
* Tolerate one test dose (15g) of ascorbate.
* Not pregnant.

Exclusion Criteria:

* Recurrent high grade glioma
* G6PD (glucose-6-phosphate dehydrogenase) deficiency.
* Patients actively receiving insulin or using a finger-stick glucometer daily for blood glucose measurements
* 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: warfarin, flecainide, methadone, amphetamines, quinidine, and chlorpropamide.
* Known active concurrent malignancy, as determined by treating physicians.
* 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 RT fields.
* Patients receiving any other investigational agents (imaging agents are acceptable)
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection that would result in a hospital stay or delay of treatment, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or impact patient safety.
* Pregnant women.
* Breastfeeding women.
* Known HIV-positive individuals. High-dose ascorbate acid is a known CYP450 3A4 inducer, which results in lower serum levels of antiretroviral drugs.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: monthly up to 5 years post treatment
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: monthly up to 5 years post treatment
measure: Adverse Event Frequency
timeFrame: monthly through 7 months post-radiation
Other outcomes:
measure: Health-related Quality of Life (HRQOL)
timeFrame: monthly for 3 months, then every 3 months up to 5 years post treatment
Locations:
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center
state: Iowa
Study officials:
affiliation: Assistant Professor, Department of Radiation Oncology, The University of Iowa
name: Bryan G. Allen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schoenfeld JD, Sibenaller ZA, Mapuskar KA, Wagner BA, Cramer-Morales KL, Furqan M, Sandhu S, Carlisle TL, Smith MC, Abu Hejleh T, Berg DJ, Zhang J, Keech J, Parekh KR, Bhatia S, Monga V, Bodeker KL, Ahmann L, Vollstedt S, Brown H, Shanahan Kauffman EP, Schall ME, Hohl RJ, Clamon GH, Greenlee JD, Howard MA, Schultz MK, Smith BJ, Riley DP, Domann FE, Cullen JJ, Buettner GR, Buatti JM, Spitz DR, Allen BG. O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. Cancer Cell. 2017 Apr 10;31(4):487-500.e8. doi: 10.1016/j.ccell.2017.02.018. Epub 2017 Mar 30.