Bevacizumab and Irinotecan to Treat Brain Tumors

NCT00393094 | Terminated Phase 2 Results

• 2 other identifiers: 06025006-C-0250
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief 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 and human clinical trials.
• Irinotecan causes damage to the deoxyribonucleic acid (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 National Cancer Institute (NCI) trial 06-C-0064 (NCT00271609), "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
• Magnetic Resonance Imaging (MRI) scan of the head every 4 weeks.
• Routine lab every week.
• Quality-of-life questionnaire every 4 weeks

Conditions

High-Grade Gliomas

Keywords

Brain Tumor; Chemotherapy; Progression; Radiotherapy; Antiangiogenesis; Glioma

Outcome Measures

Primary Outcomes (4)

• Radiographic Response Rate (Malignant Glioma Participants)

  Definition of response: complete response (CR) is the complete disappearance of all measurable and evaluable disease. Partial response (PR) is greater than or equal to a 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable lesions. Stable/No response (SD, NR)does not qualify for CR, PR, or progression. Progression is a 25% increase in the sum of products of all measurable lesions (or two target lesions if too numerous over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline.

  23 months (date of first enrollment to 1 month after last progression)

• Number of Participants With Toxicity as Measured by The National Cancer Institute (NCI) Common Toxicity Criteria v. 3.0.

  Here is the number of participants with any toxicity, defined as any adverse events possibly, probably or definitely related to the investigational drugs. For the detailed list of investigational new drug (IND)-related toxicities and other serious adverse events, see the adverse event module.

  23 months (date of first enrollment to 1 month after last progression)

• Radiographic Response Rate (Anaplastic Glioma Participants)

  Definition of response: complete response (CR) is the complete disappearance of all measurable and evaluable disease. Partial response (PR) is greater than or equal to a 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable lesions. Stable/No response (SD, NR)does not qualify for CR, PR, or progression. Progression is a 25% increase in the sum of products of all measurable lesions (or two target lesions if too numerous over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline.

  23 months (date of first enrollment to 1 month after last progression)

• Radiographic Response Rate (Glioblastoma Multiforme Participants)

  Definition of response: complete response (CR) is the complete disappearance of all measurable and evaluable disease. Partial response (PR) is greater than or equal to a 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable lesions. Stable/No response (SD, NR)does not qualify for CR, PR, or progression. Progression is a 25% increase in the sum of products of all measurable lesions (or two target lesions if too numerous over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline.

  23 months (date of first enrollment to 1 month after last progression)

Study Arms (1)

Bevacizumab & Irinotecan Patients

EXPERIMENTAL

Bevacizumab - 10 mg/kg intravenous injection Irinotecan - 125 mg/m\^2 if patient is on a non-enzyme inducing anti-epileptic drugs 340 mg/m\^2 if patient is on enzyme inducing anti-epileptic drugs every two weeks on a 4 week cycle

Biological: Bevacizumab; Drug: Irinotecan hydrochloride

Interventions

Bevacizumab BIOLOGICAL

10 mg/kg intravenous injection

Also known as: rhuMAb VEGF

Bevacizumab & Irinotecan Patients

Irinotecan hydrochloride DRUG

125 mg/m\^2 if patient is on a non-enzyme inducing anti-epileptic drugs 340 mg/m\^2 if patient is on enzyme inducing anti-epileptic drugs every two weeks on a 4 week cycle

Also known as: irinotecan hydrochloride trihydrate, CPT-11, Camptosar

Bevacizumab & Irinotecan Patients

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 been treated on the National Cancer Institute (NCI) trial 06-C-0064 (NCT00271609); bevacizumab alone for recurrent gliomas and now have evidence for tumor progression by magnetic resonance imaging (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 computed tomography (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 magnetic resonance (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 durable power of attorney (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 (white blood cell (WBC) greater than or equal 3,000/microl, absolute neutrophil count (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 (serum glutamic oxaloacetic transaminase (SGOT) and bilirubin less than 2.5 times upper limits of normal (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.
• 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.

You may not qualify if:

• 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, cyclooxygenase-2 (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 day (D)1 therapy
• Patients with clinically significant cardiovascular disease:
• History of cerebrovascular accident (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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• 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. doi: 10.1126/science.3107130.

  PMID: 3107130 BACKGROUND

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

  PMID: 3001489 BACKGROUND

• Moss AR. Occupational exposure and brain tumors. J Toxicol Environ Health. 1985;16(5):703-11. doi: 10.1080/15287398509530780.

  PMID: 4093991 BACKGROUND

• Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, Park J, Albert PS, Fine HA. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009 Feb 10;27(5):740-5. doi: 10.1200/JCO.2008.16.3055. Epub 2008 Dec 29.

  PMID: 19114704 BACKGROUND

• Kreisl TN, Zhang W, Odia Y, Shih JH, Butman JA, Hammoud D, Iwamoto FM, Sul J, Fine HA. A phase II trial of single-agent bevacizumab in patients with recurrent anaplastic glioma. Neuro Oncol. 2011 Oct;13(10):1143-50. doi: 10.1093/neuonc/nor091. Epub 2011 Aug 24.

  PMID: 21865400 RESULT

Related Links

• NIH Clinical Center Detailed Web Page
• Medline Plus
• Drug Information
• US FDA Resources

MeSH Terms

Conditions

Brain Neoplasms; Disease Progression; Glioma

Interventions

Bevacizumab; Irinotecan

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds

Limitations and Caveats

Evaluating combination therapy, 19 GBM patients were enrolled. Accrual was terminated after it became clear that we could not reach our efficacy rule of 3 or more of 29 patients responding. The AG arm never fully accrued before the study was closed.

Results Point of Contact

• Title: Howard A. Fine, M.D.
• Organization: National Cancer Institute, National Institutes of Health

hfine@mail.nih.gov

301-402-6383

Study Officials

• Howard A Fine, M.D.

  National Cancer Institute, National Institutes of Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: October 25, 2006
• First Posted: October 26, 2006
• Study Start: September 1, 2006
• Primary Completion: January 1, 2010
• Study Completion: March 1, 2010
• Last Updated: July 13, 2012
• Results First Posted: July 6, 2012

Record last verified: 2012-07

Locations

US (1)