Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02168270
Recruitment Status : Terminated
First Posted : June 20, 2014
Results First Posted : February 23, 2018
Last Update Posted : February 23, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Nicole Shonka, University of Nebraska

Tracking Information
First Submitted Date  ICMJE May 29, 2014
First Posted Date  ICMJE June 20, 2014
Results First Submitted Date  ICMJE January 25, 2018
Results First Posted Date  ICMJE February 23, 2018
Last Update Posted Date February 23, 2018
Study Start Date  ICMJE June 2014
Actual Primary Completion Date August 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 16, 2014)
  • 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 Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02168270 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 25, 2018)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2014)
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Temozolomide and Ascorbic Acid in Treating Patients With Recurrent High-Grade Glioma
Official Title  ICMJE 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 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Anaplastic Astrocytoma
  • Anaplastic Oligodendroglioma
  • Anaplastic Oligoastrocytoma
  • Glioblastoma
  • Gliosarcoma
Intervention  ICMJE
  • Dietary Supplement: ascorbic acid
    Given IV
    Other Names:
    • C-Long
    • Ce-Vi-Sol
    • Cecon
    • Cenolate
    • Cetane
  • Drug: temozolomide
    Given PO
    Other Names:
    • SCH 52365
    • Temodal
    • Temodar
    • TMZ
  • Other: quality-of-life assessment
    Ancillary studies
    Other Name: quality of life assessment
  • Other: laboratory biomarker analysis
    Correlative studies
Study Arms  ICMJE 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.
Interventions:
  • Dietary Supplement: ascorbic acid
  • Drug: temozolomide
  • Other: quality-of-life assessment
  • Other: laboratory biomarker analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 25, 2018)
4
Original Estimated Enrollment  ICMJE
 (submitted: June 16, 2014)
21
Actual Study Completion Date  ICMJE August 2015
Actual Primary Completion Date August 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 19 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02168270
Other Study ID Numbers  ICMJE 735-13
NCI-2014-01061 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
735-13 ( Other Identifier: University of Nebraska Medical Center )
P30CA036727 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Nicole Shonka, University of Nebraska
Study Sponsor  ICMJE University of Nebraska
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Nicole Shonka University of Nebraska
PRS Account University of Nebraska
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP