Protocol Number: 06-C-0250

Title:

A Phase II Trial of Bevacizumab and Irinotecan for Patients with Recurrent High-Grade Gliomas Immediately Following Tumor Progression After Treatment w/Bevacizumab Alone: A Companion Trial to NCI Study 06-C-0064 (Bevacizumab Alone for Recurrent Gliomas)

Number:

06-C-0250

Summary:

Background:

-Bevacizumab is a genetically engineered antibody that blocks the growth of new blood vessels in tumors. It has shown activity against human brain tumors in laboratory tests.

-Irinotecan causes damage to the DNA in cancer cells so that the cells cannot reproduce or repair themselves. It is approved for treating patients with colorectal cancer.

-Bevacizumab and irinotecan in combination are more effective against colon cancer than either drug alone.

Objectives:

-To determine the safety of bevacizumab and irinotecan and any side effects associated with the combination of the two drugs when given to patients with high grade gliomas.

-To determine if the combination of bevacizumab and irinotecan can help patients with brain tumors that have grown after treatment with bevacizumab alone.

Eligibility:

-Patients 18 years of age and older who have been treated on NCI protocol 06-C-0064, "Bevacizumab Alone for Recurrent Gliomas," and whose tumor has progressed.

Design:

Participants receive infusions of bevacizumab and irinotecan through a vein once every 2 weeks in 4-week treatment cycles, plus the following procedures:

-History, physical and neurological examinations every 2 weeks for the first treatment cycle and then every 4 weeks

-MRI scan of the head every 4 weeks.

-Routine lab every week.

-Quality-of-life questionnaire every 4 weeks

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Patients must have been treated on the NCI trial 06-C-0064; bevacizumab alone for recurrent gliomas and now have evidence for tumor progression by MRI scan.

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 MRI or 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 must be greater than or equal to 18 years old, and with a life expectancy greater than 8 weeks.

All patients or their previously designated DPA (if the patient is deemed by the treating physician to be impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable) must sign an informed consent indicating that they are aware of the investigational nature of this study.

Patients must have a Karnofsky performance status of greater than or equal to 60.

Patients must not be more than 4 weeks since their last bevacizumab treatment and may have received no form of treatment (i.e. radiation, chemotherapy, surgery, investigational therapy) for their progressive tumor between their last bevacizumab treatment and enrollment of this companion trial.

Patients must have adequate bone marrow function (WBC greater than or equal 3,000/microl, ANC greater than or equal to1,500/mm(3), platelet count of greater than to or equal 100,000/mm(3), and hemoglobin greater than or equal to 10 gm/dl), adequate liver function (SGOT and bilirubin less than 2.5 times ULN), and adequate renal function (creatinine less than 1.5 mg/dL and/or creatinine clearance greater than or equal to 60 cc/min) before starting therapy. These tests must be performed within 14 days prior to registration. Eligibility level for hemoglobin may be reached by transfusion.

Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patients' ability to tolerate this therapy.

This study was designed to include women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender. No exclusion to this study will be based on race.

Urine protein should be screened by dipstick or urine analysis for Urine Protein Creatinine (UPC) ratio. For proteinuria greater than or equal to 1+ or urine protein:creatinine UPC ratio greater than 1.0, 24-hour urine protein should be obtained and the level should be less than 1000 mg for patient enrollment.

Subjects must be willing and able to practice adequate contraception.

EXCLUSION CRITERIA:

Concurrent use of other standard chemotherapeutics or investigative agents.

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.

Concurrent anti-coagulation or anti-platelet medication (including aspirin, non-steroidal anti-inflammatories, COX-2 inhibitors).

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

History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days.

Invasive procedures defined as follows:

-Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy

-Anticipation of need for major surgical procedures during the course of the study

-Core biopsy within 7 days prior to D1 therapy

Patients with clinically significant cardiovascular disease:

-History of CVA within 6 months

-Uncontrolled hypertension (greater than 150/100 mmHg)

-Myocardial infarction or unstable angina within 6 months

-New York heart association grade II or greater congestive heart failure

-Serious cardiac arrhythmia requiring medication

-Unstable angina pectoris

-Clinically significant peripheral vascular disease

Clinical evidence of bleeding diathesis or coagulopathy.

Patients with known hypersensitivity of Chinese hamster ovary cell products or other recombinant human antibodies.

Special Instructions:

Currently Not Provided

Keywords:

Brain Tumor

Chemotherapy

Progression

Radiotherapy

Antiangiogenesis

Recruitment Keyword(s):

Brain Tumor

Glioma

Condition(s):

High-Grade Gliomas

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

Drug: Bevacizumab

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):

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.

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

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

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Networks and Applications, CC.

Search The Studies | Help | Questions |
Clinical Center Home | NIH Home

National Institutes of Health Clinical Center Bethesda, Maryland 20892. Last update: 09/20/2008