Bevacizumab for Recurrent Malignant Glioma

NCT00271609 | Completed Phase 2 Results

• 2 other identifiers: 06006406-C-0064
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Bevacizumab is a genetically engineered antibody that blocks the growth of new blood vessels in tumors. Inhibiting the formation of these blood vessels may slow or stop disease progression by diminishing the supply of life-sustaining nutrients and oxygen the blood delivers to the tumor. Bevacizumab is approved for treating colorectal cancer and has shown activity against brain tumor cells in laboratory and animal tests. Objectives: To examine the safety and side effects of bevacizumab in patients with recurrent brain tumors. To determine the anti-tumor activity of bevacizumab in patients with recurrent brain tumors. Eligibility: Patients 18 years of age and older with a brain tumor that continues to grow after receiving standard treatments. Design: Patients complete the following procedures during the study:

• Infusions of bevacizumab through a vein once every 2 weeks in 4-week treatment cycles.
• Positron emission tomography (PET) scan before the first dose of bevacizumab, at the end of the first treatment cycle, and as needed after that.
• Magnetic resonance imaging (MRI) scan before the first dose of bevacizumab, within 48-96 hours after the first dose of bevacizumab in the first treatment cycle, and then every 4 weeks. One tube of blood for research is collected at the time of each MRI scan to look at specific cells.
• Physical and neurological examinations every 2 weeks for the first treatment cycle and then every 4 weeks.
• Quality-of-life questionnaires every 4 weeks.

Conditions

Recurrent High-Grade Gliomas; Malignant Gliomas

Keywords

AVASTIN; Recurrence; Chemotherapy; Anti-Angiogenesis; Radiotherapy; Brain Tumor; Malignant Glioma

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Progression Free Survival at 6 Months.

  Percentage of participants surviving without progression of disease after six months of study entry. Progression is defined as a 25% increase in lesions, clear worsening of any evaluable disease, or appearance of any new lesion/site (e.g. by computed tomography, magnetic resonance imaging), or failure to return for evaluation due to death or deteriorating condition.

  6 months

• Number of Participants With Adverse Events

  Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.

  5 years

Study Arms (2)

Anaplastic Glioma (AG)

OTHER

Anaplastic astrocytoma Anaplastic oligodendroglioma Anaplastic mixed oligoastrocytoma Malignant astrocytoma (not otherwise specified) 10 mg/kg intravenously over 90 minutes every 2 weeks on a 28 day cycle. First dose is given over 90 minutes and subsequent doses are given over 30 minutes.

Drug: Bevacizumab

Glioblastoma Multiforme (GBM)

OTHER

Glioblastoma multiforme Gliosarcoma 10 mg/kg intravenously over 90 minutes every 2 weeks on a 28 day cycle. First dose is given over 90 minutes and subsequent doses are given over 30 minutes.

Drug: Bevacizumab

Interventions

Bevacizumab DRUG

10 mg/kg intravenously over 90 minutes every 2 weeks on a 28 day cycle. First dose is given over 90 minutes and subsequent doses are given over 30 minutes.

Also known as: rhuMAb VEGF

Anaplastic Glioma (AG); Glioblastoma Multiforme (GBM)

Eligibility Criteria

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

You may qualify if:

• Patients with histologically proven intracranial malignant glioma will be eligible for this protocol.
• Malignant glioma include glioblastoma multiforme (GBM),
• gliosarcoma,
• anaplastic astrocytoma (AA),
• anaplastic oligodendroglioma (AO),
• anaplastic mixed oligoastrocytoma (AMO),
• or malignant astrocytoma NOS (not otherwise specified).
• Patients must have evidence for tumor progression by magnetic resonance imaging (MRI) or computed tomography (CT) scan.
• This scan should be performed within 14 days prior to registration and on a fixed dose of steroids for at least 5 days.
• If the steroid dose is increased between the date of imaging and registration a new baseline MR/CT is required.
• The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement.
• Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:
• They have recovered from the effects of surgery.
• Residual disease following resection of recurrent tumor is not mandated for eligibility into the study.
• To best assess the extent of residual disease post-operatively, a CT/ MRI should be done:

You may not qualify if:

• Patients who, in the view of the treating physician,
• have significant active cardiac,
• hepatic,
• renal,
• or psychiatric diseases are ineligible.
• No concurrent use of other standard chemotherapeutics or investigative agents.
• Patients known to have a malignancy that has required treatment in the last 12 months and/or is expected to require treatment in the next 12 months (except non-melanoma skin cancer or carcinoma in-situ in the cervix).
• Patients who have an active infection.
• Pregnant (positive pregnancy test) or nursing women.
• Both fertile men and women must agree to use adequate contraceptive measures during study therapy and for at least 6 months after the completion of bevacizumab therapy.
• Patients who have any disease that will obscure toxicity.
• Patients with evidence of acute intracranial/intratumoral hemorrhage on pre-study CT scan.
• Concurrent anti-coagulation or anti-platelet medication (including aspirin, -non-steroidal anti-inflammatories,
• cyclooxygenase 2 (COX-2) inhibitors).
• Serious or non-healing wound,

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• Barker D, Wright E, Nguyen K, Cannon L, Fain P, Goldgar D, Bishop DT, Carey J, Baty B, Kivlin J, et al. Gene for von Recklinghausen neurofibromatosis is in the pericentromeric region of chromosome 17. Science. 1987 May 29;236(4805):1100-2. doi: 10.1126/science.3107130.

  PMID: 3107130 BACKGROUND

• Bigner SH, Bjerkvig R, Laerum OD. DNA content and chromosomal composition of malignant human gliomas. Neurol Clin. 1985 Nov;3(4):769-84.

  PMID: 3001489 BACKGROUND

• Moss AR. Occupational exposure and brain tumors. J Toxicol Environ Health. 1985;16(5):703-11. doi: 10.1080/15287398509530780.

  PMID: 4093991 BACKGROUND

• Kreisl TN, Zhang W, Odia Y, Shih JH, Butman JA, Hammoud D, Iwamoto FM, Sul J, Fine HA. A phase II trial of single-agent bevacizumab in patients with recurrent anaplastic glioma. Neuro Oncol. 2011 Oct;13(10):1143-50. doi: 10.1093/neuonc/nor091. Epub 2011 Aug 24.

  PMID: 21865400 RESULT

• Odia Y, Shih JH, Kreisl TN, Fine HA. Bevacizumab-related toxicities in the National Cancer Institute malignant glioma trial cohort. J Neurooncol. 2014 Nov;120(2):431-40. doi: 10.1007/s11060-014-1571-6. Epub 2014 Aug 7.

  PMID: 25098701 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page
• Common Terminology Criteria for Adverse Events (CTCAE)v3.0
• Response criteria for malignant gliomas
• Criteria for malignant brain tumors

MeSH Terms

Conditions

Glioma; Recurrence; Brain Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Teri Kreisl, M.D.
• Organization: National Cancer Institute, National Institutes of Health

kreislt@mail.nih.gov

301-402-3423

Study Officials

• Teri Kreisl, M.D.

  National Cancer Institute, National Institutes of Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 31, 2005
• First Posted: January 2, 2006
• Study Start: December 1, 2005
• Primary Completion: March 1, 2011
• Study Completion: February 1, 2014
• Last Updated: April 29, 2014
• Results First Posted: June 8, 2012

Record last verified: 2014-04

Locations

US (1)