Anaplastic AstrocytomaPhase 1NCT02168270
Temozolomide and Ascorbic Acid in Treating Patients With Recurrent High-Grade Glioma
A Phase 1 study testing ascorbic acid, temozolomide and quality-of-life assessment in people with Anaplastic Astrocytoma and Anaplastic Oligodendroglioma, run by University of Nebraska at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Anaplastic Oligoastrocytoma
- What is being tested?
- ascorbic acid, temozolomide and quality-of-life assessment
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Jun 2014to 20 Aug 2015
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Nebraska Medical Center
Omaha, Nebraska, 68198
About this study
Official title: A Phase I Study of Metronomic Temozolomide and Intravenous Ascorbic Acid for Patients With Recurrent High Grade Glioma
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:
- 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:
- 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.
- Conditions
- Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Anaplastic Oligoastrocytoma, Glioblastoma, Gliosarcoma
- Being tested
- ascorbic acid, temozolomide, quality-of-life assessment, laboratory biomarker analysis
- Medical subject headings
- Astrocytoma, Oligodendroglioma, Glioblastoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ascorbic acidDietary supplement
Also called C-Long, Ce-Vi-Sol, Cecon, Cenolate
Given IV
temozolomideDrug
Also called SCH 52365, Temodal, Temodar, TMZ
Given PO
quality-of-life assessmentOther
Also called quality of life assessment
Ancillary studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Dietary Supplement: ascorbic acid; Drug: temozolomide; Other: quality-of-life assessment; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
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.
Measured: Baseline to up to 52 weeks
Using Radiologic Measurements for Tumor Response
The measurement of effect will be based on the Macdonald criteria
Measured: Up to 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2014 (estimated)
- Study start16 Jun 2014
- Primary completion20 Aug 2015
- Study completion20 Aug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Anaplastic AstrocytomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Nicole Shonka, MD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02168270
- Sponsor's protocol ID
- 0735-13-FB
- Other IDs
- NCI-2014-01061, P30CA036727
- Status last verified
- Nov 2023
- First submitted
- 29 May 2014
- Last updated
- 24 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Metronomic Temozolomide and Intravenous Ascorbic Acid for Patients With Recurrent High Grade Glioma
- ClinicalTrials.gov ID
- NCT02168270
- Acronym / sponsor ID
- 0735-13-FB
- Conditions
- Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Anaplastic Oligoastrocytoma, Glioblastoma, Gliosarcoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 16 Jun 2014 (actual)
- Primary completion
- 20 Aug 2015 (actual)
- Study completion
- 20 Aug 2015 (actual)
- First posted
- 20 Jun 2014 (estimated)
- Results
- Posted 23 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (ascorbic acid, temozolomide) | Experimental | Dietary Supplement: ascorbic acid, Drug: temozolomide, Other: quality-of-life assessment, Other: laboratory biomarker analysisPatients 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. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ascorbic acidAlso: C-Long, Ce-Vi-Sol, Cecon, CenolateGiven IV | Dietary supplement | Treatment (ascorbic acid, temozolomide) |
| temozolomideAlso: SCH 52365, Temodal, Temodar, TMZGiven PO | Drug | Treatment (ascorbic acid, temozolomide) |
| quality-of-life assessmentAlso: quality of life assessmentAncillary studies | Other | Treatment (ascorbic acid, temozolomide) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (ascorbic acid, temozolomide) |
Primary outcome
Maximum Tolerated Dose of Ascorbic Acid in Combination With Temozolomide
Time frame: 56 days
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.
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.
2 secondary outcomes
Changes in Serum Levels of Ascorbic Acid Using High-performance Liquid Chromatography (HPLC) With Coulometric Electrochemical Detection)
Time frame: Baseline to up to 52 weeks
Using Radiologic Measurements for Tumor Response
Time frame: Up to 52 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicole Shonka, MD principal investigator
University of Nebraska
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ascorbic acid, temozolomide and quality-of-life assessment in people with Anaplastic Astrocytoma and Anaplastic Oligodendroglioma, run by University of Nebraska at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose of Ascorbic Acid in Combination With Temozolomide (time frame: 56 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2023.