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

NCT02833701 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: 0769-15-FBNCI-2016-00239P30CA036727
• Study Type: interventional
• Target: 9
• 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 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.

Conditions

Glioblastoma; Glioma

Outcome Measures

Primary Outcomes (4)

• Frequency of occurrence of overall toxicity

  Categorized by toxicity grades

  Up to 52 weeks

• Incidence of dose limiting toxicities (DLT)

  Described by dose level

  Up to 56 days

• Incidence rates of adverse events

  Described by dose level

  Up to 52 weeks

• 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

  Up to 56 days

Secondary Outcomes (5)

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

  Week 1 to up to Week 52

• Disease status by radiologic assessment

  Up to 56 days

• Progression free survival

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

• QOL using EORTC QLQ-C30

  Up to 52 weeks

• Survival

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

Study Arms (1)

Treatment (bevacizumab and ascorbic acid)

EXPERIMENTAL

Patients 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.

Dietary Supplement: Ascorbic Acid; Biological: Bevacizumab; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment

Interventions

Ascorbic Acid DIETARY_SUPPLEMENT

Given IV

Also known as: 2-(1,2-dihydroxyethyl)-4,5-dihydroxy-furan-3-one, Asorbicap, C Vitamin, C-Long, Ce-Vi-Sol, Cecon, Cenolate, Cetane, Cevalin, L-Ascorbic Acid, VIT C, Vitamin C, Vitamin-C

Treatment (bevacizumab and ascorbic acid)

Bevacizumab BIOLOGICAL

Given intravenously (IV)

Also known as: Anti-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-VEGF

Treatment (bevacizumab and ascorbic acid)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (bevacizumab and ascorbic acid)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (bevacizumab and ascorbic acid)

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 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)

You may not qualify if:

• 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

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

Glioblastoma; Glioma

Interventions

Ascorbic Acid; Bevacizumab; Immunoglobulin G; Disulfides

Condition Hierarchy (Ancestors)

Astrocytoma; 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; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds

Study Officials

• Nicole A Shonka, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

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 10, 2016
• First Posted: July 14, 2016
• Study Start: March 1, 2016
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: October 24, 2023

Record last verified: 2023-10

Locations

US (1)