Brain and Central Nervous System Tumors
Conditions
Keywords
adult glioblastoma, adult gliosarcoma, recurrent adult brain tumor, adult anaplastic astrocytoma, adult giant cell glioblastoma
Brief summary
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well bevacizumab works in treating patients with recurrent or progressive glioma.
Detailed description
OBJECTIVES: * Determine the safety of single-agent bevacizumab in the treatment of patients with recurrent or progressive malignant glioma. * Determine the efficacy of bevacizumab, in terms of progression-free survival at 6 months, in these patients. * Assess changes in tumoral blood flow based on magnetic resonance (MR) perfusion and tissue changes by MR spectroscopy. OUTLINE: This is a pilot study. Patients receive bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study.
Interventions
BIOLOGICALbevacizumab
Bevacizumab 15 mg/kg every 3 weeks over 30 to 90 minutes. One cycle = 3 weeks. Treatment continues until progressive disease or unacceptable toxicity.
Sponsors
National Cancer Institute (NCI)
Northwestern University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed malignant glioma, including the following: * Glioblastoma multiforme * Gliosarcoma * Anaplastic astrocytoma or anaplastic glioma * Malignant glioma not otherwise specified * Evidence of tumor recurrence or progression by MRI or CT scan with contrast * CT scan or MRI must be performed ≤ 96 hours post-operatively (≤ 2 weeks prior to study registration) or 4-6 weeks post-operatively to assess residual disease in patients who have undergone recent resection of recurrent or progressive tumor * Steroid dosage must have been stable for ≥ 5 days * Failed ≥ 1 prior systemic treatment with chemotherapy or biologic agents (excluding polifeprosan 20 with carmustine implant \[Gliadel wafers\]) * Failed prior external-beam radiotherapy * If received prior interstitial brachytherapy or stereotactic radiosurgery, true progressive disease (rather than radiation necrosis) must be confirmed by positron emission tomography, single-photon emission computer tomography with thallium, magnetic resonance (MR) spectroscopy, MR perfusion, or surgical documentation PATIENT CHARACTERISTICS: * Karnofsky performance status 70-100% * Life expectancy \> 8 weeks * WBC \> 3,000/mm³ * Absolute neutrophil count \> 1,500/mm³ * Platelet count \> 100,000/mm³ * Hemoglobin \> 10 g/dL (transfusion allowed) * SGOT and SGPT \< 1.5 times upper limit of normal (ULN) * Bilirubin \< 1.5 times ULN * Creatinine \< 1.5 mg/dL * Blood pressure ≤ 150/100 mm Hg * No unstable angina * No New York Heart Association class II-IV congestive heart failure * No stroke or myocardial infarction within the past 6 months * No clinically significant peripheral vascular disease * No evidence of bleeding diathesis or coagulopathy * Urine protein:creatinine ratio \< 1.0 * No significant medical illness that would preclude study participation or cannot be adequately controlled with appropriate therapy * No other serious medical illness or infection * No disease that would obscure toxicity or dangerously alter drug metabolism * No significant traumatic injury within the past 28 days * No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months * No serious, nonhealing wound, ulcer, or bone fracture * No history of any other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix) unless cancer is in complete remission and patient is off all therapy for that cancer for ≥ 3 years * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: * See Disease Characteristics * More than 4 weeks since prior surgery for recurrent or progressive disease and recovered * More than 28 days since prior major surgical procedure or open biopsy * At least 4 weeks since prior cytotoxic therapy (6 weeks for nitrosoureas) * At least 2 weeks since prior vincristine * At least 3 weeks since prior procarbazine hydrochloride * At least 1 week since prior noncytotoxic agents (e.g., interferon, tamoxifen, thalidomide, or isotretinoin) * Radiosensitizer does not count * At least 4 weeks since prior experimental biologic agents (e.g., epidermal growth factor receptor \[EGFR\] inhibitors) * More than 7 days since prior minor surgery, such as fine-needle aspirations or core biopsies * No concurrent combination anti-retroviral therapy for HIV-positive patients * No concurrent enzyme-inducing anticonvulsants (EIACs) * Patients on EIACs must switch to nonenzyme-inducing convulsants ≥ 2 weeks prior to study enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Treatment | From treatment initiation, throughout treatment and up to 30 days post-treatment, for up to 1 year. | Safety of treatment will be defined by the number of patients that experience grade 3 and 4 adverse events where causal relationship with bevacizumab cannot be completely ruled out. Adverse events will be graded using Common Terminology Criteria for Adverse Events v3.0 (CTCAE) where: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE |
| Progression-free Survival at 6 Months | After all patients have surpassed the 6 month post-treatment timepoint | The number of patients experiencing progression free survival (PFS) was calculated at the 6-month time point. |
| Tumoral Blood Flow Changes | Before and after treatment | To assess changes in tumoral blood flow based on MR Perfusion and tissue changes by MR spectroscopy. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from the Neuro-Oncology outpatient clinic and inpatient services between the dates of March 16, 2006 and June 5, 2008.
Participants by arm
| Arm | Count |
|---|---|
| Study Treatment All patients received bevacizumab 15 mg/kg every 3 weeks until progressive disease or unacceptable toxicity. | 55 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Study Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 48 Participants |
| Age, Continuous | 51.91 years STANDARD_DEVIATION 12.14 |
| Diagnosis Anaplastic astrocytoma (AA) | 7 Participants |
| Diagnosis Anaplastic mixed glioma | 0 Participants |
| Diagnosis Anaplastic oligodendronglioma | 4 Participants |
| Diagnosis Glioblastoma multiforme (GBM) | 44 Participants |
| Diagnosis Gliosarcoma | 0 Participants |
| Diagnosis Malignant glioma NOS (not otherwise specified) | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 47 Participants |
| Region of Enrollment United States | 55 participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 55 / 55 |
| serious Total, serious adverse events | 9 / 55 |
Outcome results
Primary
Progression-free Survival at 6 Months
The number of patients experiencing progression free survival (PFS) was calculated at the 6-month time point.
Time frame: After all patients have surpassed the 6 month post-treatment timepoint
Population: 1 patient became deceased due to toxicity prior to the 6 month time point and thus, was not evaluable for the 6 month progression free survival endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab Treatment | Progression-free Survival at 6 Months | # of Patients Who Progressed Prior to 6 months | 41 Participants |
| Bevacizumab Treatment | Progression-free Survival at 6 Months | # of Patients Experiencing PFS at 6 months | 13 Participants |
Primary
Safety of Treatment
Safety of treatment will be defined by the number of patients that experience grade 3 and 4 adverse events where causal relationship with bevacizumab cannot be completely ruled out. Adverse events will be graded using Common Terminology Criteria for Adverse Events v3.0 (CTCAE) where: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE
Time frame: From treatment initiation, throughout treatment and up to 30 days post-treatment, for up to 1 year.
Population: All patients that receive at least one dose of study treatment are evaluable for toxicity
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab Treatment | Safety of Treatment | Headache | 1 participants |
| Bevacizumab Treatment | Safety of Treatment | Bowel perforation | 1 participants |
| Bevacizumab Treatment | Safety of Treatment | DVT | 1 participants |
| Bevacizumab Treatment | Safety of Treatment | Fatigue | 5 participants |
| Bevacizumab Treatment | Safety of Treatment | Lack of drive | 1 participants |
| Bevacizumab Treatment | Safety of Treatment | Rectal bleeding | 2 participants |
Primary
Tumoral Blood Flow Changes
To assess changes in tumoral blood flow based on MR Perfusion and tissue changes by MR spectroscopy.
Time frame: Before and after treatment
Population: This was an optional outcome measure. Data was not collected or analyzed for this outcome measure.