Brain Cancer, Malignant Glioma
Conditions
Keywords
Radiation, BEVACIZUMAB, AVASTIN, TEMOZOLOMIDE, newly diagnosed, Glioblastoma, GBM, malignant glioma, Radiotherapy, 08-126
Brief summary
The purpose of this study is to test the safety of a new plan for treating glioblastoma. The usual first treatment for glioblastoma is to give focused radiation over 6 weeks in combination with a chemotherapy called temozolomide. In this study the radiation will be given over 2 weeks in combination with temozolomide and another drug, bevacizumab, will also be given. Our idea is that this treatment plan may attack both the tumor and the blood vessels feeding the tumor more effectively. This study will look at what effects, good or bad, this approach has on the patient and the tumor.
Interventions
OTHERradiotherapy (RT) in combination with temozolomide and bevacizumab
Bevacizumab10 mg/kg IV once every two weeks on days 1 and 15 of every cycle (Cycle defined as 28 days). Temozolomide 75mg/m2 daily beginning on day 1 through completion of radiotherapy. Hypofractionated dose painting IMRT will start on day 1 and will be delivered on a Monday, Wednesday, Friday schedule for a total of 6 fractions. Post RT therapy: Bevacizumab 10mg/kg IV every two weeks. Temozolomide 150-200mg/m2 daily for 5 consecutive days will be given on 28 day cycles. Follow up: CBC weekly, comprehensive panel and urinalysis monthly, blood pressure every other week. Neurological/physical examination monthly. Gd-enhanced MRI with perfusion every 2 cycles. Neurocognitive testing (approximately 4months post RT, 1 year after diagnosis and then annually in long term survivors). Blood sample for correlative studies monthly.
Sponsors
Genentech, Inc.
National Institutes of Health (NIH)
Memorial Sloan Kettering Cancer Center
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
* Pathologic diagnosis of glioblastoma or grade IV glioma. * Tumor volume should be less than 60 cc (approximately 5cm maximum diameter). * Age \> or = to 18 * KPS ≥70 * Granulocyte count \>1.5 X 10 9/L * Platelet count \>99 X 10 9/L * SGOT \< 2.5X upper limit of normal (ULN) * Serum creatinine \< 2X ULN * Bilirubin \< 2X ULN * All patients must sign written informed consent
Exclusion criteria
* Any prior chemotherapy, radiotherapy and biologic therapy for glioma. * Any prior experimental therapy for glioma. * Multicentric glioma * Other concurrent active malignancy (with the exception of cervical carcinoma in situ or basal cell ca of the skin). * Serious medical or psychiatric illness that would in the opinion of the investigator interfere with the prescribed treatment. * Pregnant or breast feeding women. * Refusal to use effective contraception * Inadequately controlled hypertension (defined as systolic blood pressure \>150 mmHg and/or diastolic blood pressure \> 100 mmHg) * Prior history of hypertensive crisis or hypertensive encephalopathy * New York Heart Association (NYHA) Grade II or greater congestive heart failure * History of myocardial infarction or unstable angina within 12 months prior to Day 1 * History of stroke or transient ischemic attack * Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1 * History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1 * Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of treatment or anticipation of need for major surgical procedure during the course of the study * Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1 * History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1 * Serious, non-healing wound, active ulcer, or untreated bone fracture * Proteinuria as demonstrated by a UPC ratio ≥ 1.0 at screening * Known hypersensitivity to any component of bevacizumab
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | through study completion, an average of 1 year | Safety assessments and toxicity grading will follow CTCAE Version 4 Grade |
Secondary
| Measure | Time frame |
|---|---|
| Progression Free Survival | through study completion, an average of 1 year |
| Neurocognitive Outcome | through study completion, an average of 1 year |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RT, With Temozolomide and Bevacizumab This treatment regimen is novel in that it delivers the initial course of RT over 2 weeks instead of 6 weeks; also, the addition of bevacizumab during and after RT is a new approach.
Bevacizumab10 mg/kg IV once every two weeks on days 1 and 15 of every cycle (Cycle defined as 28 days). Temozolomide 75mg/m2 daily beginning on day 1 through completion of radiotherapy. Hypofractionated dose painting IMRT will start on day 1 and will be delivered on a Monday, Wednesday, Friday schedule for a total of 6 fractions. | 40 |
| Total | 40 |
Baseline characteristics
| Characteristic | RT, With Temozolomide and Bevacizumab |
|---|---|
| Age, Continuous | 55 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 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 | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 36 Participants |
| Region of Enrollment United States | 40 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 40 / 40 |
| other Total, other adverse events | 40 / 40 |
| serious Total, serious adverse events | 19 / 40 |
Outcome results
Primary
Number of Participants With Adverse Events
Safety assessments and toxicity grading will follow CTCAE Version 4 Grade
Time frame: through study completion, an average of 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RT, With Temozolomide and Bevacizumab | Number of Participants With Adverse Events | 40 Participants |
Secondary
Neurocognitive Outcome
Time frame: through study completion, an average of 1 year
Population: 37 participants agreed to undergo neuropsychological evaluations.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RT, With Temozolomide and Bevacizumab | Neurocognitive Outcome | Neuropsychological evaluations | 37 Participants |
| RT, With Temozolomide and Bevacizumab | Neurocognitive Outcome | Did not agree to neuropsychological evaluations | 3 Participants |
Secondary
Progression Free Survival
Time frame: through study completion, an average of 1 year
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RT, With Temozolomide and Bevacizumab | Progression Free Survival | 10 months |