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GlioblastomaPhase 1NCT02833701

Bevacizumab and Ascorbic Acid in Patients Treating With Recurrent High Grade Glioma

A Phase 1 study testing Ascorbic Acid, Bevacizumab and Laboratory Biomarker Analysis in people with Glioblastoma and Glioma, run by University of Nebraska at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I trial studies the side effects and best dose of ascorbic acid when given together with bevacizumab in treating patients with high grade glioma that has come back (recurrent). Monoclonal antibodies, such as bevacizumab may interfere with the ability of tumor cells to grow and spread. Read more about this study

Who is it for?
Ages 19 years and older
Conditions the study is for
Glioblastoma, Glioma
What is being tested?
Ascorbic Acid, Bevacizumab and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
Mar 2016to Mar 2019
Phase
Phase 1
Are there results?
None posted in the registry

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 who have received additional therapies for previous progressions will be considered eligible
  • 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) >= 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 transaminase (AST) and alanine transaminase (ALT) less than 1.5 times the upper limits of normal
  • Serum alkaline phosphatase less than 2.5 times the upper limits of normal
  • 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 bevacizumab or ascorbic acid
  • Known human immunodeficiency virus (HIV)-positivity AND actively being treated with highly active antiretroviral 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
  • Prior hypersensitivity to bevacizumab or toxicity requiring discontinuation of bevacizumab
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  • Clinically significant cardiovascular disease defined as follows:
  • Inadequately controlled hypertension (i.e., systolic blood pressure [SBP] > 160 mm Hg and/or diastolic pressure [DBP] > 90 mm Hg despite antihypertensive therapy)
  • History of cerebrovascular accident (CVA) within 6 months
  • Myocardial infarction or unstable angina within 6 months
  • Evidence or history of bleeding diathesis (greater than normal risk of bleeding, i.e., Hereditary Hemorrhagic Telangiectasia type I or HHT-1) or coagulopathy in the absence of therapeutic anti-coagulation or any hemorrhage/bleeding event > grade 3 within 4 weeks prior to registration; note: patients with full-dose anticoagulants are eligible provided the patient has been on a stable dose for at least 2 weeks of low molecular weight heparin; therapeutic Coumadin and aspirin doses > 325 mg daily are not allowed
  • Active wound, a serious or non-healing wound, an active ulcer or untreated bone fracture
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess =< 6 months prior to registration
  • Major surgical procedure, open biopsy or significant traumatic injury =< 28 days prior to registration
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

Other trials in United States

About this study

Official title: A Phase I Study of Bevacizumab 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 bevacizumab in treating patients with high grade glioma that has come back (recurrent). Monoclonal antibodies, such as bevacizumab may interfere with the ability of tumor cells to grow and spread. Ascorbic acid contains ingredients that may prevent or slow the growth of high grade glioma. Giving bevacizumab and ascorbic acid together may work better in treating patients with high grade glioma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the toxicities and determine the recommended dose of intravenous ascorbic acid given three times weekly in combination with intravenous bevacizumab every two weeks in patients with recurrent high grade glioma.

SECONDARY OBJECTIVES:

  1. 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 bevacizumab.

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

III. To evaluate progression-free and overall survival of patients with recurrent high grade glioma treated with therapy with ascorbic acid and bevacizumab. Patients with stable or responsive disease after every 2 cycles will continue on therapy with ascorbic acid and bevacizumab until intolerance or progressive disease.

IV. To descriptively examine quality of life (QOL) using European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire 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 (at least 24 hours apart) and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for 1 year.

Conditions
Glioblastoma, Glioma
Being tested
Ascorbic Acid, Bevacizumab, Laboratory Biomarker Analysis, Quality-of-Life Assessment
Medical subject headings
Glioblastoma, Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ascorbic AcidDietary supplement

    Also called 2-(1,2-dihydroxyethyl)-4,5-dihydroxy-furan-3-one, Asorbicap, C Vitamin, C-Long

    Given IV

  • BevacizumabBiological

    Also called Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin

    Given intravenously (IV)

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

Study groups in NCT02833701
Study groupRoleWhat they receive
Treatment (bevacizumab and ascorbic acid)ExperimentalPatients receive ascorbic acid IV over 90-120 minutes three times per week (at least 24 hours apart) and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Receives: Dietary Supplement: Ascorbic Acid; Biological: Bevacizumab; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Frequency of occurrence of overall toxicity

    Categorized by toxicity grades

    Measured: Up to 52 weeks

  2. Incidence of dose limiting toxicities (DLT)

    Described by dose level

    Measured: Up to 56 days

  3. Incidence rates of adverse events

    Described by dose level

    Measured: Up to 52 weeks

  4. Maximum tolerated dose of ascorbic acid combined with bevacizumab

    Maximum tolerated dose of ascorbic acid in combination with bevacizumab defined as the highest dose tested which results in DLT in no more than 1 of 6 evaluable patients

    Measured: Up to 56 days

Secondary outcomes (5)

  1. Changes in serum levels of ascorbic acid using HPLC with coulometric electrochemical detection

    Correlation of intracellular glutathione with ascorbic acid levels during therapy with ascorbic acid and temozolomide will be summarized using descriptive statistics to summarize changes over time.

    Measured: Week 1 to up to Week 52

  2. Disease status by radiologic assessment

    Disease status measured by radiologic assessment

    Measured: Up to 56 days

  3. Progression free survival

    Will be plotted following the method of Kaplan and Meier

    Measured: First date of therapy until the first notation of clinical progression, relapse or death from any cause, assessed up to 1 year

  4. QOL using EORTC QLQ-C30

    Will be descriptively summarized using means and standard deviations.

    Measured: Up to 52 weeks

  5. Survival

    Will be plotted following the method of Kaplan and Meier.

    Measured: First date of therapy until the date of death from any cause, assessed up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jul 2016 (estimated)
  2. Study startMar 2016
  3. Primary completionMar 2019
  4. Study completionMar 2019

Resources

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
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02833701
Sponsor's protocol ID
0769-15-FB
Other IDs
NCI-2016-00239, P30CA036727
Status last verified
Oct 2023
First submitted
10 May 2016
Last updated
24 Oct 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ascorbic Acid, Bevacizumab and Laboratory Biomarker Analysis in people with Glioblastoma and Glioma, 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 19 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 Oct 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?

The study was stopped early. Results are not available in the source record.

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?

Frequency of occurrence of overall toxicity (time frame: Up to 52 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02833701.

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 Oct 2023.

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