Bevacizumab, Temozolomide and Hypofractionated Radiotherapy for Patients With Newly Diagnosed Malignant Glioma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Other: radiotherapy (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.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Progression Free Survival [through study completion, an average of 1 year]
- Neurocognitive Outcome [through study completion, an average of 1 year]
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Memoral Sloan Kettering Cancer Center | Basking Ridge | New Jersey | United States | |
| 2 | Memorial Sloan-Kettering Cancer Center at Commack | Commack | New York | United States | 11725 |
| 3 | Memorial Sloan-Kettering Cancer Center | New York | New York | United States | 10065 |
Sponsors and Collaborators
- Memorial Sloan Kettering Cancer Center
- Genentech, Inc.
- National Institutes of Health (NIH)
Investigators
- Principal Investigator: Antonio Omuro, MD, Memorial Sloan Kettering Cancer Center
Study Documents (Full-Text)
More Information
Publications
None provided.- 08-126
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | RT, With Temozolomide and Bevacizumab |
|---|---|
| Arm/Group Description | 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. |
| Period Title: Overall Study | |
| STARTED | 40 |
| COMPLETED | 40 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | RT, With Temozolomide and Bevacizumab |
|---|---|
| Arm/Group Description | 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. |
| Overall Participants | 40 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
55
|
| Sex: Female, Male (Count of Participants) | |
| Female |
14
35%
|
| Male |
26
65%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
0
0%
|
| Not Hispanic or Latino |
40
100%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
1
2.5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
36
90%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
3
7.5%
|
| Region of Enrollment (Count of Participants) | |
| United States |
40
100%
|
Outcome Measures
| Title | Number of Participants With Adverse Events |
|---|---|
| Description | Safety assessments and toxicity grading will follow CTCAE Version 4 Grade |
| Time Frame | through study completion, an average of 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | RT, With Temozolomide and Bevacizumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 40 |
| Count of Participants [Participants] |
40
100%
|
| Title | Progression Free Survival |
|---|---|
| Description | |
| Time Frame | through study completion, an average of 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | RT, With Temozolomide and Bevacizumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 40 |
| Median (Full Range) [months] |
10
|
| Title | Neurocognitive Outcome |
|---|---|
| Description | |
| Time Frame | through study completion, an average of 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| 37 participants agreed to undergo neuropsychological evaluations. |
| Arm/Group Title | RT, With Temozolomide and Bevacizumab |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 40 |
| Neuropsychological evaluations |
37
92.5%
|
| Did not agree to neuropsychological evaluations |
3
7.5%
|
Adverse Events
| Time Frame | 1 year | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | RT, With Temozolomide and Bevacizumab | |
| Arm/Group Description | 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. | |
All Cause Mortality |
||
| RT, With Temozolomide and Bevacizumab | ||
| Affected / at Risk (%) | # Events | |
| Total | 40/40 (100%) | |
Serious Adverse Events |
||
| RT, With Temozolomide and Bevacizumab | ||
| Affected / at Risk (%) | # Events | |
| Total | 19/40 (47.5%) | |
| Blood and lymphatic system disorders | ||
| Hemoglobin | 1/40 (2.5%) | |
| Leukocytes (total WBC) | 1/40 (2.5%) | |
| Thrombotic microangiopathy | 3/40 (7.5%) | |
| Eye disorders | ||
| Ocular/Visual - Other (specify) | 1/40 (2.5%) | |
| Gastrointestinal disorders | ||
| Colitis | 1/40 (2.5%) | |
| Nausea | 3/40 (7.5%) | |
| Pain - Abdomen NOS | 1/40 (2.5%) | |
| Vomiting | 3/40 (7.5%) | |
| Infections and infestations | ||
| Infection, other | 2/40 (5%) | |
| Investigations | ||
| Creatinine | 2/40 (5%) | |
| Neutrophils/granulocytes (ANC/AGC) | 2/40 (5%) | |
| Platelets | 6/40 (15%) | |
| Musculoskeletal and connective tissue disorders | ||
| Muscle weakness - Left-sided | 1/40 (2.5%) | |
| Pain - Back | 1/40 (2.5%) | |
| Nervous system disorders | ||
| Hemorrhage, CNS | 1/40 (2.5%) | |
| Pain - Head/headache | 2/40 (5%) | |
| Pyramidal tract dysfunction | 2/40 (5%) | |
| Seizure | 13/40 (32.5%) | |
| Speech impairment | 2/40 (5%) | |
| Vasovagal episode | 1/40 (2.5%) | |
| Psychiatric disorders | ||
| Confusion | 1/40 (2.5%) | |
| Personality/behavioral | 1/40 (2.5%) | |
| Renal and urinary disorders | ||
| Glomerular filtration rate | 1/40 (2.5%) | |
| Vascular disorders | ||
| Thrombosis/thrombus/embolism | 3/40 (7.5%) | |
Other (Not Including Serious) Adverse Events |
||
| RT, With Temozolomide and Bevacizumab | ||
| Affected / at Risk (%) | # Events | |
| Total | 40/40 (100%) | |
| Eye disorders | ||
| Vision-blurred vision | 2/40 (5%) | |
| Gastrointestinal disorders | ||
| Constipation | 18/40 (45%) | |
| Nausea | 15/40 (37.5%) | |
| Diarrhea | 6/40 (15%) | |
| Mucositis oral | 12/40 (30%) | |
| Vomiting | 4/40 (10%) | |
| Hemorrhage, Oral cavity | 2/40 (5%) | |
| General disorders | ||
| Fatigue | 29/40 (72.5%) | |
| Injury, poisoning and procedural complications | ||
| Hemorrhage/Bleeding - other | 4/40 (10%) | |
| Wound complication, non-infectious | 2/40 (5%) | |
| Investigations | ||
| Leukocytes (total WBC) | 3/40 (7.5%) | |
| Neutrophils/granulocytes (ANC/AGC) | 2/40 (5%) | |
| Platelets | 2/40 (5%) | |
| Metabolism and nutrition disorders | ||
| Anorexia | 7/40 (17.5%) | |
| Musculoskeletal and connective tissue disorders | ||
| Pain - Joint | 3/40 (7.5%) | |
| Pain - neck | 2/40 (5%) | |
| Nervous system disorders | ||
| Headache | 10/40 (25%) | |
| Neuropathy - sensory | 3/40 (7.5%) | |
| Dizziness | 2/40 (5%) | |
| Memory Impairment | 2/40 (5%) | |
| Seizure | 2/40 (5%) | |
| Renal and urinary disorders | ||
| Proteinuria | 2/40 (5%) | |
| Urinary frequency/urgency | 2/40 (5%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Dyspnea | 3/40 (7.5%) | |
| Hemorrhage, Nose | 2/40 (5%) | |
| Skin and subcutaneous tissue disorders | ||
| Dermatology/Skin, other | 3/40 (7.5%) | |
| Dry Skin | 2/40 (5%) | |
| Rash/desquamation | 2/40 (5%) | |
| Vascular disorders | ||
| Hypertension | 4/40 (10%) | |
| Thrombosis/thrombus/embolism | 2/40 (5%) | |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Philip Gutin |
|---|---|
| Organization | Memorial Sloan Kettering Cancer Center |
| Phone | 212-639-8556 |
| gutinp@mskcc.org |
- 08-126