Clinical Trials /

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

NCT02833701

Description:

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.

Related Conditions:
  • Malignant Glioma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Bevacizumab and Ascorbic Acid in Patients Treating With Recurrent High Grade Glioma
  • Official Title: A Phase I Study of Bevacizumab and Intravenous Ascorbic Acid for Patients With Recurrent High Grade Glioma

Clinical Trial IDs

  • ORG STUDY ID: 769-15
  • SECONDARY ID: NCI-2016-00239
  • SECONDARY ID: 769-15-FB
  • SECONDARY ID: 769-15
  • SECONDARY ID: P30CA036727
  • NCT ID: NCT02833701

Conditions

  • Glioblastoma
  • Glioma

Interventions

DrugSynonymsArms
BevacizumabAnti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGFTreatment (bevacizumab and ascorbic acid)

Purpose

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.

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 intravenous bevacizumab every two weeks 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 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.
    

Trial Arms

NameTypeDescriptionInterventions
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.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  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
    
              -  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)
    
            Exclusion Criteria:
    
              -  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
    
              -  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
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:19 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Frequency of occurrence of overall toxicity
    Time Frame:Up to 52 weeks
    Safety Issue:
    Description:Categorized by toxicity grades.

    Secondary Outcome Measures

    Measure:Changes in serum levels of ascorbic acid using HPLC with coulometric electrochemical detection
    Time Frame:Week 1 to up to Week 52
    Safety Issue:
    Description: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.
    Measure:Disease status by radiologic assessment
    Time Frame:Up to 56 days
    Safety Issue:
    Description:Disease status measured by radiologic assessment.
    Measure:Progression free survival
    Time Frame:First date of therapy until the first notation of clinical progression, relapse or death from any cause, assessed up to 1 year
    Safety Issue:
    Description:Will be plotted following the method of Kaplan and Meier.
    Measure:QOL using EORTC QLQ-C30
    Time Frame:Up to 52 weeks
    Safety Issue:
    Description:Will be descriptively summarized using means and standard deviations.
    Measure:Survival
    Time Frame:First date of therapy until the date of death from any cause, assessed up to 1 year
    Safety Issue:
    Description:Will be plotted following the method of Kaplan and Meier.

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:University of Nebraska

    Last Updated