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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)


Phase 2
18 Years
N/A
Not Enrolling
Both
High-Grade Gliomas

Thank you

Trial Information

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 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.

Inclusion Criteria


- INCLUSION CRITERIA:

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.

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, 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

- 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.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Radiographic Response Rate (Malignant Glioma Participants)

Outcome Description:

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.

Outcome Time Frame:

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

Safety Issue:

No

Principal Investigator

Howard A Fine, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute, National Institutes of Health

Authority:

United States: Federal Government

Study ID:

060250

NCT ID:

NCT00393094

Start Date:

September 2006

Completion Date:

March 2010

Related Keywords:

  • High-Grade Gliomas
  • Brain Tumor
  • Chemotherapy
  • Progression
  • Radiotherapy
  • Antiangiogenesis
  • Glioma
  • Brain Neoplasms
  • Glioma

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892