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

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase I Study of Metronomic Temozolomide and Intravenous Ascorbic Acid for Patients With Recurrent High Grade Glioma

Brief 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.

Detailed Summary:

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.

Sponsor: University of Nebraska

Current Primary Outcome:

• 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 [ Time Frame: 56 days ]
  Graded by the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events version 4.0. DLT incidence will be described by dose level.
• Incidence rates of adverse events, graded according to the NCI Common Toxicity Criteria for Adverse Events version 4.0 [ Time Frame: Up to 30 days after last administration of study medication ]
  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.

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Changes in serum levels of ascorbic acid (using HPLC with coulometric electrochemical detection) [ Time Frame: Baseline to up to 52 weeks ]
  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.
• Using radiologic measurements for tumor response [ Time Frame: Up to 52 weeks ]
  The measurement of effect will be based on the Macdonald criteria
• Progression-free survival (PFS) [ Time Frame: First date of therapy until the first notation of clinical progression, relapse or death from any cause, assessed up to 5 years ]
  PFS curves will be plotted following the method of Kaplan and Meier.
• Overall survival (OS) [ Time Frame: First date of therapy until the date of death from any cause, assessed up to 5 years ]
  OS curves will be plotted following the method of Kaplan and Meier.
• Quality of life, assessed by the EORTC QLQ-C30 [ Time Frame: Up to 52 weeks ]
  Will be descriptively summarized using means and standard deviations.

Original Secondary Outcome:

• Changes in serum levels of ascorbic acid (using HPLC with coulometric electrochemical detection) [ Time Frame: Baseline to up to 52 weeks ]
  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.
• Using radiologic measurements for tumor response [ Time Frame: Up to 52 weeks ]
  The measurement of effect will be based on the Macdonald Criteria.
• Progression-free survival (PFS) [ Time Frame: First date of therapy until the first notation of clinical progression, relapse or death from any cause, assessed up to 5 years ]
  PFS curves will be plotted following the method of Kaplan and Meier.
• Overall survival (OS) [ Time Frame: First date of therapy until the date of death from any cause, assessed up to 5 years ]
  OS curves will be plotted following the method of Kaplan and Meier.
• Quality of life, assessed by the EORTC QLQ-C30 [ Time Frame: Up to 52 weeks ]
  Will be descriptively summarized using means and standard deviations.

Information By: University of Nebraska

Dates:
Date Received: May 29, 2014
Date Started: June 2014
Date Completion:
Last Updated: December 3, 2015
Last Verified: December 2015