A Study of Gliadel Followed by Avastin + Irinotecan for Glioblastoma Multiforme (GBM) - Full Text View

Sponsor:	Duke University
Collaborators:	Eisai Inc. Genentech
Information provided by:	Duke University
ClinicalTrials.gov Identifier:	NCT00735436

Purpose

The primary objective of the study is to use 24 week survival to assess the efficacy of the combination of Gliadel followed by Avastin and irinotecan in the treatment of grade IV malignant glioma patients following surgical resection. The secondary objectives are to determine the progression-free survival following the combination of Gliadel followed by Avastin and irinotecan and to describe the toxicity of Gliadel followed by Avastin and irinotecan.

Condition	Intervention	Phase
Malignant Glioma Glioblastoma Multiforme Gliosarcoma	Other: Taking EIAEDs (enzyme-inducing anticonvulsant medications) Other: NOT taking EIAEDs	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study
Official Title:	Phase II Trial for Patients With Glioblastoma Multiforme (GBM) Treated With Gliadel Followed by Avastin Plus Irinotecan

Resource links provided by NLM:

Drug Information available for: Phenobarbital Phenobarbital sodium Irinotecan U 101440E Irinotecan hydrochloride Bevacizumab Carmustine

U.S. FDA Resources

Further study details as provided by Duke University:

Primary Outcome Measures:

To use 24-week survival to assess the efficacy of the combination of Gliadel followed by Avastin and irinotecan in the treatment of grade IV malignant glioma patients following surgical resection. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine the progression-free survival following the combination of Gliadel followed by Avastin and irinotecan [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
To describe the toxicity of Gliadel followed by Avastin and irinotecan. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	50
Study Start Date:	December 2008
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Taking enzyme-inducing anticonvulsant medications Subjects taking enzyme-inducing anticonvulsant medications (EIAEDs) such as dilantin, tegretol, or phenobarbital.	Other: Taking EIAEDs (enzyme-inducing anticonvulsant medications) Those subjects who are taking EIAEDs (enzyme-inducing anticonvulsant medications) such as dilantin, tegretol, or phenobarbital.
NOT taking enzyme-inducing anticonvulsant medications Subjects NOT taking enzyme-inducing anticonvulsant medications such as dilantin, tegretol, or phenobarbital.	Other: NOT taking EIAEDs Subjects NOT taking EIAEDs (enzyme-inducing anticonvulsant medications such as dilantin, tegretol, or phenobarbital.

Detailed Description:

This is a phase II study of the combination of Gliadel followed by Avastin and irinotecan in grade IV malignant glioma patients. The study will have survival and toxicity endpoints. Subjects will be identified by the investigator as those patients who have histologically documented grade IV malignant glioma (glioblastoma multiforme or gliosarcoma) with recurrent or progressive disease who are able to undergo a GTR (gross total resection).

Phase I: Gliadel wafer- 1-8 wafers inserted at time of gross total resection. Treatment cycle is 42 days in length. For patients with ≥ Grade 1 toxicity will allow 84 days prior to beginning therapy with Avastin and CPT-11.

Phase II: Avastin Plus Irinotecan (Cycles 1-12) consists of the following (cycle length is 6 weeks):

Irinotecan 125 mg/m2 (not taking EIAEDs) or 340 mg/m2 (taking EIAEDs) given every two weeks on days 1, 15, 29, etc.;
If the patient has the UGT 1A1 polymorphism (7/7), they do not metabolize the irinotecan normally, so these patients will start out at a two dose level reduction; For patients on an EIAED, the starting dose will be 275 mg/M2, and for patients not on an EIAED, the starting dose will be 75 mg/M2;
Avastin 10 mg/kg immediately after the irinotecan given every 2 weeks on days 1, 15, 29, etc.

The primary objective of this phase II study is to determine whether the administration of Gliadel wafers followed by Avastin and irinotecan to patients with recurrent GBM is a treatment regimen worthy of further investigation in a randomized clinical trial. The basis for making this decision will be the proportion of patients who survive at least 24 weeks after initiation of protocol treatment.

In the initial Phase I and II clinical trials, four potential Avastin-associated safety signals were identified: hypertension, proteinuria, thromboembolic events, and hemorrhage. The two major toxicities associated with irinotecan are myelosuppression and diarrhea. Side effects associated with Gliadel are seizures, brain edema (swelling), healing abnormalities, wound infection and body pain.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients must have histologically confirmed diagnosis of WHO grade IV primary malignant glioma (glioblastoma multiforme or gliosarcoma). Patients have to be able to undergo a GTR.
Age > or = 18 years
Evidence of a unilateral, single focus of measurable CNS neoplasm on contrast-enhanced MRI, unless medically contraindicated (CT scan will then be used)
Patients must have < or = 2 disease progressions
An interval of at least 4 weeks from the end of prior radiotherapy or one week from the end of a cycle of chemotherapy and enrollment on this protocol
Karnofsky > or = 70%
Hemoglobin > or = 9.0 g/dl, ANC > or = 1,500 cells/microliters, platelets > or = 125,000 cells/microliters
Serum creatinine < or = 1.5 mg/dl, serum SGOT and bilirubin < or = 1.5 times upper limit of normal
Patients on corticosteroids must have been on a stable dose for 1 week prior to entry, if clinically possible, and the dose should not be escalated over entry dose level
If patient received chemotherapy or investigational agent as part of their prior therapy, the patient must recover from all toxicities (> or = Grade 1) prior to enrollment on this protocol
Signed informed consent approved by the Institutional Review Board
No evidence of CNS hemorrhage on the baseline MRI or CT scans
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. Women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to treatment administration
Multifocal disease
Prior treatment with Gliadel
Prior treatment with CPT-11 or Avastin
Prior stereotactic radiosurgery or brachytherapy
Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids
Active infection requiring IV antibiotics
Acute or chronic renal insufficiency (a GFR <30 mL/min/1.73m2) or acute renal insufficiency of any severity due to hepato-renal syndrome or in the peri-operative liver transplantation period
Inability, in the opinion of the study investigator, to comply with study and/or follow-up procedures
Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored Avastin cancer study
Life expectancy of less than 12 weeks
Active malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within last five years
Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg)
Prior history of hypertensive crisis or hypertensive encephalopathy
New York Heart Association (NYHA) Grade II or greater congestive heart failure
History of myocardial infarction or unstable angina within 6 months prior to Day 1
History of stroke or transient ischemic attack within 6 months prior to Day 1
Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
History of hemoptysis (> or = 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
History of abdominal fistula, gastrointestinal perforation within 6 months prior to Day 1
Serious, non-healing wound, active ulcer, or untreated bone fracture
Proteinuria at screening as demonstrated by urinalysis (urine protein)
Known hypersensitivity to any component of Avastin
Pregnancy (positive pregnancy test) or lactation. Use of effective means of contraception (men and women) in subjects of child-bearing potential

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00735436

Contacts

Contact: James J Vredenburgh, MD	919-681-3824	vrede001@mc.duke.edu
Contact: Mary Lou Affronti, RN, MSN, ANP	919-684-6239	affro002@mc.duke.edu

Locations

United States, North Carolina
Duke University Medical Center	Recruiting
Durham, North Carolina, United States, 27710
Contact: James J Vredenburgh, MD 919-681-3824 vrede001@mc.duke.edu
Contact: Sarah Woodring, BS 919-684-2527 sarah.woodring@duke.edu
Principal Investigator: James J Vredenburgh, MD
Sub-Investigator: Mary Lou Affronti, RN, MSN, ANP

Sponsors and Collaborators

Duke University

Eisai Inc.

Genentech

Investigators

Principal Investigator:

James J Vredenburgh, MD

Duke University

More Information

Additional Information:

Duke University Medical Center Clinical Trials This link exits the ClinicalTrials.gov site

The Preston Robert Tisch Brain Tumor Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Duke University Medical Center ( James Joseph Vredenburgh, MD )
Study ID Numbers:	00006308
Study First Received:	August 13, 2008
Last Updated:	August 4, 2009
ClinicalTrials.gov Identifier:	NCT00735436 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Duke University:

Malignant glioma
Glioblastoma multiforme
GBM
Gliosarcoma
Gliadel
Carmustine

Irinotecan
CPT-11
Camptosar
Avastin
Bevacizumab

Additional relevant MeSH terms:

Glioblastoma
Phenobarbital
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
GABA Modulators
Neoplasms, Nerve Tissue
Irinotecan
Physiological Effects of Drugs
Excitatory Amino Acid Agents
Bevacizumab
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Hypnotics and Sedatives
Growth Inhibitors

Angiogenesis Modulating Agents
Glioma
Excitatory Amino Acid Antagonists
Neoplasms by Histologic Type
Astrocytoma
Growth Substances
Central Nervous System Depressants
Enzyme Inhibitors
Angiogenesis Inhibitors
Pharmacologic Actions
Neuroectodermal Tumors
Neoplasms
GABA Agents
Neoplasms, Neuroepithelial
Gliosarcoma

ClinicalTrials.gov processed this record on February 08, 2010