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

NCT00597402 | Completed Phase 2 Results DMC

• 1 other identifier: Pro00000458
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Glioblastoma; Gliosarcoma; Brain Tumor

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 16-month Overall Survival (OS)

  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.

  16 months

Secondary Outcomes (3)

• 12-month Progression-free Survival (PFS)

  12 months

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

  55 months

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

  55 months

Study Arms (1)

Avastin, radiation, temozolomide, and irinotecan

EXPERIMENTAL

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

Interventions

Avastin DRUG

Avastin will be administered 10 mg/kg every other week beginning a minimum of 28 days after last major surgical procedure, open biopsy, or significant traumatic injury. Following completion of XRT, patients will receive treatment that includes 6 cycles of Avastin, beginning a minimum of 14 days after last XRT.

Also known as: Bevacizumab

Avastin, radiation, temozolomide, and irinotecan

Temozolomide DRUG

Daily temozolomide 75 mg/m2/day for 6.5 weeks of radiation treatment. Following completion of XRT, patients will receive treatment including temozolomide 200 mg/m2/day on the 1st 5 days of each 28-day cycle.

Also known as: Temodar

Avastin, radiation, temozolomide, and irinotecan

Radiation Therapy (XRT) RADIATION

Treatment with standard XRT (radiation) for 6.5 weeks.

Avastin, radiation, temozolomide, and irinotecan

Irinotecan DRUG

Following completion of XRT, patients will receive 6 cycles of treatment that includes irinotecan. Beginning a minimum of 14 days after last XRT, the irinotecan dose will depend on whether the patient is on enzyme-inducing antiepileptic drugs (EIAED). (EIAED:340 mg/m2 every other week, non-EIAED: 125 mg/m2.)

Also known as: CPT-11, Camptosar

Avastin, radiation, temozolomide, and irinotecan

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• Genentech, Inc.: collaborator
• Schering-Plough: collaborator

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Brain Tumor Center at DUKE

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Brain Neoplasms; Glioma

Interventions

Bevacizumab; Temozolomide; Radiotherapy; Irinotecan

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; 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; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Camptothecin; Alkaloids

Results Point of Contact

• Title: Annick Desjardins, MD, FRCPC
• Organization: Duke University Medical Center

annick.desjardins@duke.edu

9196846173

Study Officials

• Annick Desjardins, MD, FRCPC

  Duke Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2008
• First Posted: January 18, 2008
• Study Start: July 1, 2007
• Primary Completion: August 1, 2011
• Study Completion: May 1, 2013
• Last Updated: May 7, 2014
• Results First Posted: January 18, 2013

Record last verified: 2014-04

Locations

US (1)