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High-Grade GliomasPhase 2NCT00393094

Bevacizumab and Irinotecan to Treat Brain Tumors

A Phase 2 study testing Bevacizumab and Irinotecan hydrochloride in people with High-Grade Gliomas, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
High-Grade Gliomas
What is being tested?
Bevacizumab and Irinotecan hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
1 siteUnited States
Study dates
Sep 2006to Mar 2010
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • 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.

Who cannot join

  • 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.
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  • 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
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official 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 (NCT00271609)(Bevacizumab Alone for Recurrent Gliomas)

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.
Read more

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
Read the detailed description

Background:

  • Bevacizumab is a humanized IgG1 monoclonal antibody (MAb) that binds all biologically active isoforms of human vascular endothelial growth factor (VEGF, or VEGF-A) with high affinity (kd = 1.1 nM ). The antibody consists of a human IgG1 framework and the antigen-binding complementarity-determining regions from the murine anti-VEGF MAb A.4.6.1.
  • Irinotecan is a semisynthetic derivative of camptothecin that possesses greater aqueous solubility, greater in vitro and in vivo activity, and is associated with less severe and more predictable toxicity than camptothecin.
  • We now propose treating patients whose tumors progress on our bevacizumab alone protocol with the combination of bevacizumab with irinotecan. We believe that this trial design has significant power to detect a true synergistic effect between the two agents given that the single agent activity of irinotecan is so low in patients with recurrent malignant gliomas (2-5% response rate) and the patients being treated on this trial will have tumors that have already progressed through bevacizumab.

Objective:

  • To establish data and safety regarding the anti-tumor activity of bevacizumab plus irinotecan in patients with recurrent high-grade gliomas that have progressed on bevacizumab alone as determined by objective radiographic response rate.
  • To determine the 6 month progression-free survival of treated patients and to characterize the pattern of changes in the number of endothelial progenitor cells over time and across patients.
  • To obtain preliminary data regarding how response to treatment (stable disease or radiographic response) effects monthly measurements of quality of life while on study.

Eligibility:

  • Patients must have been treated on the National Cancer Institute (NCI) trial 06-C-0064; 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.

Design:

-Patients will be treated with bevacizumab by intravenous injection at a dose of 10mg/kg and irinotecan at a dose of 125 mg/m^2 for patients on non-enzyme-inducing anti-epileptic drugs (NEIAED) and 340 mg/m^2 for patients on enzyme-inducing anti-epileptic drugs (EIAED) every two weeks on a 4-week cycle.

Keywords
Brain Tumor, Chemotherapy, Progression, Radiotherapy, Antiangiogenesis, Glioma
Medical subject headings
Brain Neoplasms, Disease Progression, Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BevacizumabBiological

    Also called rhuMAb VEGF

    10 mg/kg intravenous injection

  • Irinotecan hydrochlorideDrug

    Also called irinotecan hydrochloride trihydrate, CPT-11, Camptosar

    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

Study groups in NCT00393094
Study groupRoleWhat they receive
Bevacizumab & Irinotecan PatientsExperimentalBevacizumab - 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
Receives: Biological: Bevacizumab; Drug: Irinotecan hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

  3. 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.

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

  4. 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Oct 2006 (estimated)
  2. Study startSep 2006
  3. Primary completionJan 2010
  4. Study completionMar 2010

Why it stopped: Terminated due to the limitations of accrual.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00393094
Sponsor's protocol ID
060250
Other IDs
06-C-0250
Status last verified
Jul 2012
First submitted
25 Oct 2006
Last updated
13 Jul 2012
Data monitoring committee
No

Publications

  • 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.

    PubMed 3107130

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

    PubMed 3001489

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

    PubMed 4093991

  • 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.

    PubMed 19114704

  • 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.

    PubMed 21865400

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bevacizumab and Irinotecan hydrochloride in people with High-Grade Gliomas, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 13 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Jul 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Radiographic Response Rate (Malignant Glioma Participants) (time frame: 23 months (date of first enrollment to 1 month after last progression)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00393094, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2012.

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