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

Study Purpose

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).

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

 No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

 Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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.
  • - 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

 NCT01752491
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

 Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

 Joseph J. Cullen, MD, FACS
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

 John M. Buatti, MDJoseph J Cullen, MD
Principal Investigator Affiliation Department of Radiation Oncology, The University of IowaProfessor of Surgery, The University of Iowa
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

 Other, NIH
Overall Status Completed
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

 Glioblastoma, GBM, Glioblastoma Multiforme
Additional Details

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.

Arms & Interventions

Arms

Experimental: 15g Ascorbate

During radiation therapy: - Radiation: 61.2 Gray (1.8 Gray / fraction / day), 5 days/week, for approximately 8 weeks. - Temozolomide: 75 mg/m2, taken orally, once daily, every day, until radiation is completed. - Ascorbate: 15 g administered by IV three times a week until 1 month after radiation is completed (approximately 12 weeks). After radiation therapy: - Temozolomide: Starting 1 month after radiation. 150 mg/m2 and then 200 mg/m2 daily. Starting 28 days after the completion of radiation therapy. Taken for 5 days followed by 23 days of rest for 6 cycles. - Ascorbate: escalating weekly doses of ascorbate (up to 125 grams) to target a serum level of 350 mg/dL (20 mM). Ascorbate is administered twice weekly, each week, for up to 6 months.

Experimental: 25g Ascorbate

If the 15g arm is tolerated, the study opens the 25g arm. During radiation therapy: - Radiation: 61.2 Gray (1.8 Gy/fraction/day), 5 days/wk, for about 8 weeks. - Temozolomide: 75 mg/m2, taken orally, once every day, until radiation is completed. - Ascorbate: 25 g administered by IV three times/wk until 1 month after radiation is completed (about 12 weeks). After radiation therapy: - Temozolomide: Starting 1 month after radiation. 150 mg/m2 and then 200 mg/m2 daily. Starting 28 days after the completion of radiation therapy. Taken for 5 days followed by 23 days of rest for 6 cycles. - Ascorbate: escalating weekly doses of ascorbate (up to 125 grams) to target a serum level of 350 mg/dL (20 mM). Ascorbate is administered twice weekly, each week, for up to 6 months.

Experimental: 50g arm

If the 25g arm is tolerated, the study opens the 50g arm. During radiation therapy: - Radiation: 61.2 Gray (1.8 Gy/fraction/day), 5 days/wk, for about 8 weeks. - Temozolomide: 75 mg/m2, taken orally, once every day, until radiation is completed. - Ascorbate: 50 g administered by IV three times a week until 1 month after radiation is completed (about 12 weeks). After radiation therapy: - Temozolomide: Starting 1 month after radiation. 150 mg/m2 and then 200 mg/m2 daily. Starting 28 days after the completion of radiation therapy. Taken for 5 days followed by 23 days of rest for 6 cycles. - Ascorbate: escalating weekly doses of ascorbate (up to 125 grams) to target a serum level of 350 mg/dL (20 mM). Ascorbate is administered twice weekly, each week, for up to 6 months.

Experimental: 62.5g

If the 50g arm is tolerated, the study opens the 62.5g arm. During radiation therapy: - Radiation: 61.2 Gray (1.8 Gy/fraction/day), 5 days/wk, for about 8 weeks. - Temozolomide: 75 mg/m2, taken orally, once every day, until radiation is completed. - Ascorbate: 62.5 g administered by IV three times a week until 1 month after radiation is completed (about 12 weeks). After radiation therapy: - Temozolomide: Starting 1 month after radiation. 150 mg/m2 and then 200 mg/m2 daily. Starting 28 days after the completion of radiation therapy. Taken for 5 days followed by 23 days of rest for 6 cycles. - Ascorbate: escalating weekly doses of ascorbate (up to 125 grams) to target a serum level of 350 mg/dL (20 mM). Ascorbate is administered twice weekly, each week, for up to 6 months.

Experimental: 75g Ascorbate

If the 62.5g arm is tolerated, the study opens the 75g arm. During radiation therapy: - Radiation: 61.2 Gray (1.8 Gy/fraction/day), 5 days/wk, for about 8 weeks. - Temozolomide: 75 mg/m2, taken orally, once every day, until radiation is completed. - Ascorbate: 75 g administered by IV three times a week until 1 month after radiation is completed (about 12 weeks). After radiation therapy: - Temozolomide: Starting 1 month after radiation. 150 mg/m2 and then 200 mg/m2 daily. Starting 28 days after the completion of radiation therapy. Taken for 5 days followed by 23 days of rest for 6 cycles. - Ascorbate: escalating weekly doses of ascorbate (up to 125 grams) to target a serum level of 350 mg/dL (20 mM). Ascorbate is administered twice weekly, each week, for up to 6 months.

Experimental: 87.5g Ascorbate

If the 75g arm is tolerated, the study opens the 87.5g arm. During radiation therapy: - Radiation: 61.2 Gray (1.8 Gy/fraction/day), 5 days/wk, for about 8 weeks. - Temozolomide: 75 mg/m2, taken orally, once every day, until radiation is completed. - Ascorbate: 87.5 g administered by IV three times a week until 1 month after radiation is completed (about 12 weeks). After radiation therapy: - Temozolomide: Starting 1 month after radiation. 150 mg/m2 and then 200 mg/m2 daily. Starting 28 days after the completion of radiation therapy. Taken for 5 days followed by 23 days of rest for 6 cycles. - Ascorbate: escalating weekly doses of ascorbate (up to 125 grams) to target a serum level of 350 mg/dL (20 mM). Ascorbate is administered twice weekly, each week, for up to 6 months.

Interventions

Drug: - Ascorbate

Intravenous infusion of high-dose ascorbate

Drug: - Temozolomide

Oral chemotherapeutic

Radiation: - Radiation therapy

External beam radiation therapy

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Iowa City, Iowa

Status

Address

Holden Comprehensive Cancer Center at the University of Iowa

Iowa City, Iowa, 52242

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