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Avastin in Combination With Radiation and Temozolomide, Followed by Avastin, Temozolomide and Irinotecan for Glioblastoma Multiformes and Gliosarcomas

Phase 2
18 Years
Open (Enrolling)
Glioblastoma, Gliosarcoma, Brain Tumor

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Trial Information

Avastin in Combination With Radiation and Temozolomide, Followed by Avastin, Temozolomide and Irinotecan for Glioblastoma Multiformes and Gliosarcomas

The standard of care for grade IV gliomas is radiation therapy with daily temozolomide,
followed by 6 months of temozolomide. The majority of patients progress and die of their
tumor. Many glioma patients are resistant to temozolomide because the tumors have high
O(6)-methylguanine-DNA methyltransferase (MGMT), conferring resistance. Irinotecan is
synergistic with temozolomide, and the combination may overcome high MGMT. Vascular
endothelial growth factor (VEGF) is present on the cell surface and around malignant
gliomas. It appears that the presence of vascular endothelial growth factor is a prognostic
growth factor with more VEGF expression correlating with a poor prognosis. Monoclonal
antibodies to VEGF have inhibited growth of malignant gliomas in a mouse xenograft. Avastin
is a humanized monoclonal immunoglobulin G (IGG) 1 antibody that binds to and inhibits the
biologic activity of human vascular endothelial growth factor. The combination of Avastin
and irinotecan was safe and demonstrated high activity against recurrent malignant gliomas.
The combination of Avastin, temozolomide, and irinotecan as the initial therapy may maximize
the chance for long-term survival. There are other studies completed or ongoing for newly
diagnosed glioblastoma (GBM) patients, including a Radiation Therapy Oncology Group (RTOG)
study that added irinotecan to temozolomide following standard radiation therapy and
temozolomide, and a University of California, Los Angeles (UCLA) study that added Avastin to
standard radiation therapy and temozolomide followed by Avastin and temozolomide.

Inclusion Criteria:

- Patients must have histologically confirmed diagnosis of World Health Organization
(WHO) grade IV primary malignant glioma (glioblastoma multiforme or gliosarcoma).
Patients have to be within 4 weeks of the last major surgical procedure.

- Age > 18 years.

- An interval of at least 2 weeks and not > 6 weeks between prior major surgical
procedure and study enrollment.

- No prior radiotherapy or chemotherapy for a brain tumor

- Karnofsky ≥ 60 percent.

- Hemoglobin ≥ 9.0 g/deciliter (dl), absolute neutrophil count (ANC) ≥ 1,500 cells/
microliter, platelets ≥ 125,000 cells/microliter.

- Serum creatinine ≤ 1.5 mg/dl, serum serum glutamic-oxaloacetic transaminase (SGOT)
and bilirubin ≤ 1.5 times upper limit of normal (ULN).

- For patients on corticosteroids, they must be on a stable or decreasing dose for 1
week prior to entry, and the dose should not be escalated over entry dose level, if
clinically possible.

- Signed informed consent approved by the Institutional Review Board

- No evidence of > grade 1 central nervous system (CNS) hemorrhage on the baseline MRI
or CT scan.

- If sexually active, patients will take contraceptive measures for the duration of
treatment as stated in the informed consent.

Exclusion Criteria:

- Pregnancy or breast feeding.

- Co-medication that may interfere with study results; e.g. immuno-suppressive agents
other than corticosteroids.

- Active infection requiring intravenous (IV) antibiotics.

- Prior treatment with radiotherapy or chemotherapy for a brain tumor, irrespective of
the grade of the tumor.

- Evidence of > grade 1 CNS hemorrhage on baseline MRI on CT scan.

Avastin-Specific Concerns:

Subjects meeting any of the following criteria are ineligible for study entry:

- Current, recent (within 4 weeks of the first infusion of this study), or planned
participation in an experimental drug study

- Blood pressure of 150/100 mmHg

- Unstable angina

- New York Heart Association (NYHA) Grade II or greater congestive heart failure

- History of myocardial infarction within 6 months

- History of stroke within 6 months

- Clinically significant peripheral vascular disease

- Evidence of bleeding diathesis

- Coagulopathy (prothrombin time (PT) or partial thromboplastin time (PTT) >1.5x normal
or a history of > three grade 2 or greater hemorrhages)

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to first Avastin infusion during XRT/Temodar or anticipation of need for major
surgical procedure during the course of the study

- Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
prior to first Avastin infusion during XRT/Temodar

- Pregnant (positive pregnancy test) or lactating

- Urine protein >1.0 + at screening

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to first Avastin infusion during XRT/Temodar

- Serious, non-healing wound, ulcer, or bone fractures.

- Inability to comply with study and/or follow-up procedures.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

16-month Overall Survival (OS)

Outcome Description:

Percentage of participants surviving sixteen months from the start of study treatment. OS was defined as the time from the date of study treatment initiation to the date of death due to any cause.

Outcome Time Frame:

16 months

Safety Issue:


Principal Investigator

Annick Desjardins, MD, FRCPC

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University Health System


United States: Institutional Review Board

Study ID:




Start Date:

July 2007

Completion Date:

March 2013

Related Keywords:

  • Glioblastoma
  • Gliosarcoma
  • Brain Tumor
  • Avastin
  • Bevacizumab
  • Temozolomide
  • Temodar
  • Irinotecan
  • Camptosar
  • GBM
  • Glioblastoma Multiforme
  • Gliosarcoma
  • Brain tumor
  • Glioma
  • New GBM
  • Newly diagnosed GBM or gliosarcoma malignant brain tumor
  • Brain Neoplasms
  • Glioblastoma
  • Gliosarcoma



Duke University Health System Durham, North Carolina  27705