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TerminatedNCT02168270Updated Nov 24, 2023Results posted

Temozolomide and Ascorbic Acid in Treating Patients With Recurrent High-Grade Glioma

A Phase 1 interventional study of ascorbic acid and temozolomide in Anaplastic Astrocytoma, Anaplastic Oligodendroglioma and Anaplastic Oligoastrocytoma, sponsored by University of Nebraska. Terminated at 1 site in United States. Open to participants aged 19 Years and older. Per ClinicalTrials.gov, last updated 2023-11-24.

Sponsored by University of Nebraska · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
4
Allocation
Not applicable
Ages
19 Years and older
Sex
All
01

Study summary

This phase I trial studies the side effects and best dose of ascorbic acid when given together with temozolomide in treating patients with high-grade glioma that has come back. 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. Ascorbic acid contains ingredients that may prevent or slow the growth of high-grade gliomas. Giving temozolomide with ascorbic acid may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

I. To evaluate the toxicities and determine the recommended dose of intravenous ascorbic acid given three times weekly in combination with temozolomide in patients with recurrent high grade glioma.

SECONDARY OBJECTIVES:

I. To evaluate changes in the levels of serum ascorbic acid using high-performance liquid chromatography (HPLC) with coulometric electrochemical detection) during therapy with ascorbic acid and temozolomide.

II. Radiographic assessment of disease status after 2 cycles of therapy with ascorbic acid and temozolomide.

III. To evaluate progression-free and overall survival of patients with recurrent high grade glioma treated with therapy with ascorbic acid and temozolomide.

IV. To descriptively examine quality of life (QOL) using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 during treatment.

OUTLINE: This is a dose-escalation study of ascorbic acid.

Patients receive ascorbic acid intravenously (IV) over 90-120 minutes three times per week and temozolomide orally days 1-28. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 2 months for 1 year and then periodically thereafter.

02

Conditions studied

  • Anaplastic Astrocytoma
  • Anaplastic Oligodendroglioma
  • Anaplastic Oligoastrocytoma
  • Glioblastoma
  • Gliosarcoma
03

In context

Astrocytoma

434 studies on the registry are indexed under Astrocytoma; 79 are open to participants now.

This study's enrollment of 4 is below the median of 30 across 359 interventional studies indexed under Astrocytoma.

Browse Astrocytoma studies →

Lead sponsor

University of Nebraska is the lead sponsor of 495 studies on the registry; 68 are open to participants now.

Of its 83 completed or terminated interventional studies of FDA-regulated products, 52 (63%) have results posted.

Browse University of Nebraska studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
19 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Patients must have pathologically proven diagnosis of high grade glioma
  • Patients must have received prior radiation therapy and standard temozolomide
  • Patients must be three or more months from the end of chemoradiotherapy or have biopsy or imaging consistent with disease progression
  • Patients must have recovered from toxicity of prior therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 or better
  • Absolute neutrophil count (ANC) count >= 1,500/mm\^3
  • Hemoglobin >= 8 g/dL
  • Platelet count >= 100,000/mm\^3
  • Serum creatinine that is at or below 2.0 mg/dL
  • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 1.5 times the upper limits of normal; note: if hepatic function is abnormal, the decision to initiate temozolomide treatment should carefully consider the benefits and risks for the individual patient
  • Serum alkaline phosphatase less than 2.5 times the upper limits of normal; note: if hepatic function is abnormal, the decision to initiate temozolomide treatment should carefully consider the benefits and risks for the individual patient
  • The patient must be aware of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts
  • Women of reproductive potential must be non-pregnant and non-nursing and must agree to employ an effective barrier method of birth control throughout the study and for up to 6 months following treatment
  • Women of child-bearing potential must have a negative pregnancy test within 7 days of initiating study; (no childbearing potential is defined as age 55 years or older and no menses for two years or any age with surgical removal of the uterus and/or both ovaries)

Exclusion criteria

Exclusion Criteria:

  • History of uncontrollable allergic reactions to temozolomide or ascorbic acid or to antiemetics appropriate for administration in conjunction with protocol-directed chemotherapy
  • Known human immunodeficiency virus (HIV)-positivity AND actively being treated with highly active anti-retroviral therapy (HAART)
  • History of glucose-6-phosphate dehydrogenase deficiency
  • History of oxalate nephrolithiasis or urine oxalate > 60 mg/dL
  • Anuria, dehydration, severe pulmonary congestion or pulmonary edema or fixed low cardiac input since all are conditions for which osmotic diuresis are contraindicated and ascorbic acid has high osmolarity
  • Any other clinically significant medical disease or condition laboratory abnormality or psychiatric illness that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
  • Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide; note: high dose ascorbic acid may affect urine acidification and, as a result, may affect clearance rates of these drugs
  • Simultaneous participation in other therapeutic clinical trials will not be allowed
  • Inability to co-operate with the requirements of the protocol
  • Pregnant and nursing women are excluded from this study
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
4 participants (actual)

Study arms

  • Experimental
    Treatment (ascorbic acid, temozolomide)

    Patients receive ascorbic acid IV over 90-120 minutes three times per week and temozolomide orally days 1-28. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

    Dietary Supplement: ascorbic acid · Drug: temozolomide · Other: quality-of-life assessment · Other: laboratory biomarker analysis

Interventions

  • Dietary supplementascorbic acid

    Given IV

    Also known as: C-Long, Ce-Vi-Sol, Cecon, Cenolate, Cetane

  • Drugtemozolomide

    Given PO

    Also known as: SCH 52365, Temodal, Temodar, TMZ

  • Otherquality-of-life assessment

    Ancillary studies

    Also known as: quality of life assessment

  • Otherlaboratory biomarker analysis

    Correlative studies

06

What researchers measure

Primary outcomes

  1. Maximum Tolerated Dose of Ascorbic Acid in Combination With Temozolomide

    Maximum tolerated dose of ascorbic acid in combination with temozolomide, defined as the highest dose tested which results in dose limiting toxicity (DLT) in no more than one of six evaluable patients. Graded by the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events version 4.0. DLT incidence will be described by dose level.

    Time frame: 56 days

  2. Incidence Rates of Adverse Events, Graded According to the NCI Common Toxicity Criteria for Adverse Events Version 4.0

    The incidence rates of adverse events will be described by dose level. The frequency of occurrence of overall toxicity, categorized by toxicity grades, will be described.

    Time frame: Up to 30 days after last administration of study medication

Secondary outcomes

  1. Changes in Serum Levels of Ascorbic Acid Using High-performance Liquid Chromatography (HPLC) With Coulometric Electrochemical Detection)

    Correlation of intracellular glutathione (in peripheral blood mononuclear cells) with ascorbic acid levels during therapy with ascorbic acid and temozolomide will be summarized using descriptive statistics to summarize changes over time.

    Time frame: Baseline to up to 52 weeks

  2. Using Radiologic Measurements for Tumor Response

    The measurement of effect will be based on the Macdonald criteria

    Time frame: Up to 52 weeks

07

Results

Posted Feb 23, 2018

Participant flow

Participant flow — Overall Study
MilestoneTreatment (Ascorbic Acid, Temozolomide)
Started4
Completed0
Not completed4
Withdrew: Lack of efficacy4

Outcome measures

PrimaryMaximum Tolerated Dose of Ascorbic Acid in Combination With Temozolomide

Maximum tolerated dose of ascorbic acid in combination with temozolomide, defined as the highest dose tested which results in dose limiting toxicity (DLT) in no more than one of six evaluable patients. Graded by the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events version 4.0. DLT incidence will be described by dose level.

Time frame:
56 days

No measurements were reported for this outcome.

PrimaryIncidence Rates of Adverse Events, Graded According to the NCI Common Toxicity Criteria for Adverse Events Version 4.0

The incidence rates of adverse events will be described by dose level. The frequency of occurrence of overall toxicity, categorized by toxicity grades, will be described.

Time frame:
Up to 30 days after last administration of study medication

No measurements were reported for this outcome.

SecondaryChanges in Serum Levels of Ascorbic Acid Using High-performance Liquid Chromatography (HPLC) With Coulometric Electrochemical Detection)

Correlation of intracellular glutathione (in peripheral blood mononuclear cells) with ascorbic acid levels during therapy with ascorbic acid and temozolomide will be summarized using descriptive statistics to summarize changes over time.

Time frame:
Baseline to up to 52 weeks

No measurements were reported for this outcome.

SecondaryUsing Radiologic Measurements for Tumor Response

The measurement of effect will be based on the Macdonald criteria

Time frame:
Up to 52 weeks

No measurements were reported for this outcome.

Adverse events

Collected over Up to 52 weeks. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment (Ascorbic Acid, Temozolomide)0/4 (0%)2/4 (50%)1/4 (25%)
Most frequent serious events
Most frequent serious events
EventTreatment (Ascorbic Acid, Temozolomide)
HeadacheGeneral disorders1/4
VomitingGastrointestinal disorders1/4
HyponatremiaMetabolism and nutrition disorders1/4
SeizureNervous system disorders1/4
Pain, Hip, backMusculoskeletal and connective tissue disorders1/4
WeaknessGeneral disorders1/4
Urinary retentionRenal and urinary disorders1/4
Most frequent other events
Most frequent other events
EventTreatment (Ascorbic Acid, Temozolomide)
LymphopeniaBlood and lymphatic system disorders1/4
HyponatremiaMetabolism and nutrition disorders1/4

Baseline characteristics

Age, Continuous
Age, Continuous(years)Treatment (Ascorbic Acid, Temozolomide)
Mean42 (30 to 64)
Sex: Female, Male
Sex: Female, Male(Participants)Treatment (Ascorbic Acid, Temozolomide)
Female2
Male2
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Treatment (Ascorbic Acid, Temozolomide)
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White4
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Treatment (Ascorbic Acid, Temozolomide)
United States4
08

Study locations

1 site
  • University of Nebraska Medical Center
    Omaha, Nebraska 68198, United States
09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Jun 2014 to primary completion in Aug 2015, 14 months.

Results were first posted in Feb 2018, 2 years 6 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
May 29, 2014
First posted
Jun 20, 2014
StartActual
Jun 16, 2014
Primary completionActual
Aug 20, 2015
CompletionActual
Aug 20, 2015
Results first posted
Feb 23, 2018
Last update
Nov 24, 2023
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Nov 24, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02168270
Lead sponsor
University of Nebraska
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Jun 20, 2014
Start date
Jun 16, 2014
Primary completion
Aug 20, 2015
Completion
Aug 20, 2015
Results posted
Feb 23, 2018
Last update
Nov 24, 2023

Study contacts

Nicole Shonka, MD
principal investigator · University of Nebraska

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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