Overview

This trial is active, not recruiting.

Conditions glioblastoma, gbm, glioblastoma multiforme
Treatments ascorbate, temozolomide, radiation therapy
Phase phase 1
Sponsor University of Iowa
Collaborator National Institutes of Health (NIH)
Start date April 2013
End date November 2015
Trial size 30 participants
Trial identifier NCT01752491, 201211713, P30CA086862, U01CA140206

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).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
ascorbate Ascorbic Acid
Intravenous infusion of high-dose ascorbate
temozolomide Temodar
Oral chemotherapeutic
radiation therapy External beam radiation therapy
(Experimental)
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.
ascorbate Ascorbic Acid
Intravenous infusion of high-dose ascorbate
temozolomide Temodar
Oral chemotherapeutic
radiation therapy External beam radiation therapy
(Experimental)
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.
ascorbate Ascorbic Acid
Intravenous infusion of high-dose ascorbate
temozolomide Temodar
Oral chemotherapeutic
radiation therapy External beam radiation therapy
(Experimental)
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.
ascorbate Ascorbic Acid
Intravenous infusion of high-dose ascorbate
temozolomide Temodar
Oral chemotherapeutic
radiation therapy External beam radiation therapy
(Experimental)
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.
ascorbate Ascorbic Acid
Intravenous infusion of high-dose ascorbate
temozolomide Temodar
Oral chemotherapeutic
radiation therapy External beam radiation therapy
(Experimental)
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.
ascorbate Ascorbic Acid
Intravenous infusion of high-dose ascorbate
temozolomide Temodar
Oral chemotherapeutic
radiation therapy External beam radiation therapy

Primary Outcomes

Measure
Number of grade 3, 4, & 5 adverse events
time frame: Weekly during therapy for up to 10 months

Secondary Outcomes

Measure
Time to progression
time frame: monthly up to 5 years post treatment
Overall survival
time frame: Up to 5 years

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title A Phase I Trial of High-Dose Ascorbate in Glioblastoma Multiforme
Principal investigator John M. Buatti, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in December 2015.
Information provided to ClinicalTrials.gov by University of Iowa.
Location data was received from the National Cancer Institute and was last updated in July 2016.