Bevacizumab in Reducing CNS Side Effects in Patients Who Have Undergone Radiation Therapy to the Brain for Primary Brain Tumor, Meningioma, or Head and Neck Cancer
Study Details
Study Description
Brief Summary
Bevacizumab may reduce CNS side effects caused by radiation therapy. This randomized phase II trial is studying how well bevacizumab works in reducing CNS side effects in patients who have undergone radiation therapy to the brain for primary brain tumor, meningioma, or head and neck cancer.
Detailed Description
PRIMARY OBJECTIVE:
- Determine to what extent bevacizumab can reduce active radiation toxicity to the CNS in patients who have undergone cranial irradiation for primary brain neoplasm, meningioma, or head and neck cancer.
SECONDARY OBJECTIVES:
-
Determine to what extent this drug can reduce dexamethasone dependence in these patients.
-
Determine to what extent this drug can improve neurologic function in these patients.
-
Determine to what extent this drug can improve quality of life of these patients.
OUTLINE: This is a randomized, placebo-controlled, crossover, double-blind study. Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Patients in arm II who have failed to respond to treatment at 6 or 12 weeks may cross over to arm I and receive 2 courses of bevacizumab as in arm I. Patients in arm I (including crossover patients) who have responded to treatment may receive 2 additional courses of bevacizumab.
Patients undergo MRI after courses 2 and 4.
Quality of life and neurologic function are assessed at baseline, periodically during study treatment, and at 12 and 24 weeks after completion of study treatment.
After completion of study treatment, patients are followed at 12 and 24 weeks.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm I Patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. |
Drug: bevacizumab
Given IV
Other Names:
Procedure: magnetic resonance imaging
Other Names:
Procedure: quality-of-life assessment
Other Names:
|
| Placebo Comparator: Arm II Patients receive placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. |
Drug: placebo
Given IV
Other Names:
Procedure: magnetic resonance imaging
Other Names:
Procedure: quality-of-life assessment
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Response ( > 25% Reduction in T2 Flair) From Baseline to Evaluation at 6 Weeks Post Treatment [Baseline to 12 weeks]
Change in magnetic resonance imaging (MRI) from baseline to evaluation at 6 weeks for participants where MRI changes are based on the size of edema (T2 FLAIR) and Gd-contrast enhancement (lesion diameter and perfusion/dynamic). A 25% reduction in T2 flair volume constitutes a response for study.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
No evidence of bleeding diathesis or coagulopathy
-
Fertile patients must use effective contraception during and for >= 2 months after completion of study therapy
-
No diarrhea >= grade 1
-
Histologically confirmed primary brain neoplasm, meningioma, or head and neck cancer [WHO grade 2 or 3 disease--no WHO grade 4 primary brain neoplasms (i.e., glioblastoma or gliosarcoma)]
-
Patients with head and neck cancer must not have any of the following:
-
Evidence of metastatic disease
-
Evidence of tumor invasion to major vessels (e.g., the carotid)
-
History of bleeding related to tumor or radiotherapy during or after completion of radiotherapy
-
Must have undergone cranial irradiation
-
Must have radiographic evidence to support the diagnosis of radiation necrosis and/or surgical biopsy evidence of necrosis without tumor within the past 2 months
-
Must have evidence of progressive neurologic signs or symptoms appropriate to the location of the radiation necrosis
-
No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
-
No significant traumatic injury within the past 28 days
-
No evidence of active CNS hemorrhage
-
Karnofsky performance status 60-100%
-
No clinically significant cardiovascular disease, including any of the following:
-
Inadequately controlled hypertension (i.e., systolic BP > 140 mm Hg and/or diastolic BP > 90 mm Hg despite antihypertensive medication)
-
Large vessel cerebrovascular accident within the past 6 months
-
Myocardial infarction or unstable angina within the past 6 months
-
No clinically significant cardiovascular disease, including any of the following:
-
NYHA class II-IV congestive heart failure
-
Serious or inadequately controlled cardiac arrhythmia
-
Significant vascular disease (e.g., aortic aneurysm or history of aortic dissection)
-
Clinically significant peripheral vascular disease
-
At least 6 months since prior radiotherapy
-
Platelet count > 75,000/mm^3
-
Granulocyte count > 1,500/mm^3
-
Creatinine < 1.0 times ULN
-
AST < 2.5 times ULN
-
Not pregnant or nursing
-
Negative pregnancy test
-
Prior chemotherapy for tumor allowed
-
Prior tyrosine kinase inhibitors of VEGF receptor (VEGFR) allowed
-
More than 28 days since prior and no concurrent major surgical procedure or open biopsy
-
Concurrent dexamethasone allowed provided patient is on a stable dose for >= 1 week prior to study entry
-
Concurrent full-dose anticoagulants (e.g., warfarin) with PT INR > 1.5 allowed provided the following criteria are met:
-
In-range INR (usually between 2 and 3) and patient is on a stable dose of oral anticoagulant for 1 week or on a stable dose of low molecular weight heparin
-
No active bleeding or pathological condition that carries a high risk of bleeding
-
Concurrent full-dose anticoagulants (e.g., warfarin) with PT INR > 1.5 allowed provided the following criteria are met: No evidence of serious or nonhealing wound, ulcer, or bone fracture
-
No concurrent chemotherapy or tyrosine kinase inhibitors of VEGFR
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No prior bevacizumab
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More than 7 days since prior core biopsy
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History of seizures allowed provided the patient is receiving anticonvulsant therapy
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Hemoglobin >= 9.0 g/dL
-
Bilirubin =< 1.5 times upper limit of normal (ULN)
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No other concurrent investigational agents
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | M D Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Monica Loghin, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2009-00256
- NCI-2009-00256
- CDR0000553135
- 2006-0890
- 7955
- P30CA016672
- N01CM62202
Study Results
Participant Flow
| Recruitment Details | Recruitment Period: June 20, 2007 to December 07, 2009. All recruitment done at The University of Texas (UT) MD Anderson Cancer Center. |
|---|---|
| Pre-assignment Detail | Of the 15 patients enrolled, four participants were excluded from the study. |
| Arm/Group Title | Arm A: Bevacizumab | Crossover Arm B: Placebo First, Then Bevacizumab |
|---|---|---|
| Arm/Group Description | Bevacizumab 7.5 mg/m^2 intravenous (IV) every 3 weeks. | Placebo IV every 3 weeks for two courses, crossover at 6 weeks to receive Bevacizumab 7.5 mg/m^2 IV as in Arm A. |
| Period Title: First Intervention (6 Weeks) | ||
| STARTED | 5 | 6 |
| COMPLETED | 5 | 6 |
| NOT COMPLETED | 0 | 0 |
| Period Title: First Intervention (6 Weeks) | ||
| STARTED | 5 | 6 |
| COMPLETED | 5 | 6 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Arm A: Bevacizumab | Crossover Arm B: Placebo First, Then Bevacizumab | Total |
|---|---|---|---|
| Arm/Group Description | Bevacizumab 7.5 mg/m^2 intravenous (IV) every 3 weeks | Placebo IV every 3 weeks for two courses, crossover at 6 weeks to receive Bevacizumab 7.5 mg/m^2 IV as in Arm A | Total of all reporting groups |
| Overall Participants | 5 | 6 | 11 |
| Age (years) [Mean (Full Range) ] | |||
| Mean (Full Range) [years] |
43
|
47
|
47
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
3
60%
|
3
50%
|
6
54.5%
|
| Male |
2
40%
|
3
50%
|
5
45.5%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
5
100%
|
6
100%
|
11
100%
|
Outcome Measures
| Title | Number of Participants With Response ( > 25% Reduction in T2 Flair) From Baseline to Evaluation at 6 Weeks Post Treatment |
|---|---|
| Description | Change in magnetic resonance imaging (MRI) from baseline to evaluation at 6 weeks for participants where MRI changes are based on the size of edema (T2 FLAIR) and Gd-contrast enhancement (lesion diameter and perfusion/dynamic). A 25% reduction in T2 flair volume constitutes a response for study. |
| Time Frame | Baseline to 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was conducted per protocol. The participants in the Crossover Arm were evaluated after receiving the Bevacizumab treatment as described in the arm description. |
| Arm/Group Title | Arm A: Bevacizumab | Crossover Arm B: Placebo Then Bevacizumab |
|---|---|---|
| Arm/Group Description | Bevacizumab 7.5 mg/m^2 intravenous (IV) every 3 weeks | Placebo IV every 3 weeks for two courses, crossover at 6 weeks to receive Bevacizumab 7.5 mg/m^2 IV as in Arm A |
| Measure Participants | 5 | 6 |
| Number [participants] |
5
100%
|
6
100%
|
Adverse Events
| Time Frame | 2 years and 9 months | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Bevacizumab | Placebo | ||
| Arm/Group Description | Bevacizumab 7.5 mg/m^2 intravenous (IV) every 3 weeks | First Intervention Placebo IV (only) every 3 weeks for two courses | ||
All Cause Mortality |
||||
| Bevacizumab | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Bevacizumab | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/11 (36.4%) | 0/6 (0%) | ||
| Gastrointestinal disorders | ||||
| Dysphagia | 1/11 (9.1%) | 2 | 0/6 (0%) | 0 |
| Nervous system disorders | ||||
| Seizure | 1/11 (9.1%) | 1 | 0/6 (0%) | 0 |
| Vascular disorders | ||||
| Thrombosis | 2/11 (18.2%) | 2 | 0/6 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Bevacizumab | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/11 (45.5%) | 0/6 (0%) | ||
| Blood and lymphatic system disorders | ||||
| Thrombocytopenia | 1/11 (9.1%) | 1 | 0/6 (0%) | 0 |
| Cardiac disorders | ||||
| Hypertension | 4/11 (36.4%) | 4 | 0/6 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Nausea | 1/11 (9.1%) | 1 | 0/6 (0%) | 0 |
| General disorders | ||||
| Fatigue | 3/11 (27.3%) | 3 | 0/6 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Elevated alanine aminotransferase (ALT) | 2/11 (18.2%) | 2 | 0/6 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Monica Loghin, MD / Assistant Professor |
|---|---|
| Organization | The University of Texas MD Anderson Cancer Center |
| Phone | K Hunter, RN 713-745-5769 |
| CR_Study_Registration@mdanderson.org |
- NCI-2009-00256
- NCI-2009-00256
- CDR0000553135
- 2006-0890
- 7955
- P30CA016672
- N01CM62202