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Avastin in Combination With Radiation (XRT) & Temozolomide, Followed by Avastin, Temozolomide and Irinotecan for Glioblastoma (GBM) and Gliosarcomas

Information source: Duke University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Glioblastoma; Gliosarcoma; Brain Tumor

Intervention: Avastin (Drug); Temozolomide (Drug); Radiation Therapy (XRT) (Radiation); Irinotecan (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Duke University

Official(s) and/or principal investigator(s):
Annick Desjardins, MD, FRCPC, Principal Investigator, Affiliation: Duke University Health System

Summary

Primary objective: To use overall survival to assess the efficacy of the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan in the treatment of grade IV malignant glioma patients following surgical resection. Secondary objective: To determine the progression-free survival following the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan. Exploratory Objective: To explore the relationship between biomarkers and outcome (overall survival and progression-free survival) among patients with grade IV malignant glioma treated with radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan. To describe the toxicity of radiation therapy,temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan.

Clinical Details

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

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

Primary outcome: 16-month Overall Survival (OS)

Secondary outcome:

12-month Progression-free Survival (PFS)

Number of Patients Experiencing a Central Nervous System (CNS) Hemorrhage or a Systemic Hemorrhage

Number of Patients Experiencing a Grade ≥ 4 Hematologic or Grade ≥ 3 Non-hematologic Toxicity

Detailed description: 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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

Locations and Contacts

Duke University Health System, Durham, North Carolina 27710, United States
Additional Information

The Preston Robert Tisch Brain Tumor Center at DUKE

Starting date: July 2007
Last updated: April 22, 2014

Page last updated: August 23, 2015

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