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

NCT02168270 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: 0735-13-FBNCI-2014-01061P30CA036727
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Anaplastic Astrocytoma; Anaplastic Oligodendroglioma; Anaplastic Oligoastrocytoma; Glioblastoma; Gliosarcoma

Outcome Measures

Primary Outcomes (2)

• 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.

  56 days

• 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.

  Up to 30 days after last administration of study medication

Secondary Outcomes (2)

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

  Baseline to up to 52 weeks

• Using Radiologic Measurements for Tumor Response

  Up to 52 weeks

Study Arms (1)

Treatment (ascorbic acid, temozolomide)

EXPERIMENTAL

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

ascorbic acid DIETARY_SUPPLEMENT

Given IV

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

Treatment (ascorbic acid, temozolomide)

temozolomide DRUG

Given PO

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

Treatment (ascorbic acid, temozolomide)

quality-of-life assessment OTHER

Ancillary studies

Also known as: quality of life assessment

Treatment (ascorbic acid, temozolomide)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (ascorbic acid, temozolomide)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Nebraska: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

MeSH Terms

Conditions

Astrocytoma; Oligodendroglioma; Glioblastoma; Gliosarcoma

Interventions

Ascorbic Acid; Temozolomide

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Nicole Shonka
• Organization: University of Nebraska Medical Center

nshonka@unmc.edu

402-559-5166

Study Officials

• Nicole Shonka, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2014
• First Posted: June 20, 2014
• Study Start: June 16, 2014
• Primary Completion: August 20, 2015
• Study Completion: August 20, 2015
• Last Updated: November 24, 2023
• Results First Posted: February 23, 2018

Record last verified: 2023-11

Locations

US (1)