Bevacizumab With or Without Radiation Therapy in Treating Patients With Recurrent Glioblastoma



Status:Active, not recruiting
Conditions:Brain Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:9/7/2018
Start Date:December 20, 2012
End Date:September 2023

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RANDOMIZED PHASE II TRIAL OF CONCURRENT BEVACIZUMAB AND RE-IRRADIATION VERSUS BEVACIZUMAB ALONE AS TREATMENT FOR RECURRENT GLIOBLASTOMA

This randomized phase II trial studies how well bevacizumab with or without radiation therapy
works in treating patients with recurrent glioblastoma. 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 cancer-killing
substances to them. Specialized radiation therapy that delivers a high dose of radiation
directly to the tumor may kill more tumor cells and cause less damage to normal tissue. It is
not yet know whether bevacizumab is more effective with or without radiation therapy in
treating patients with recurrent glioblastoma

PRIMARY OBJECTIVES:

I. To establish an improvement in overall survival in recurrent glioblastoma (GBM) patients
receiving bevacizumab and re-irradiation compared with patients receiving bevacizumab alone.

SECONDARY OBJECTIVES:

I. To estimate and compare the rate of objective response in patients with measurable
disease.

II. To estimate and compare the 6-month progression-free survival rate. III. To estimate and
compare progression-free survival. IV. To estimate and compare the rate of treatment adverse
events. V. To estimate and compare the rate of grade 3+ acute or delayed central nervous
system (CNS) toxicity.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive bevacizumab intravenously (IV) over 30-90 minutes every 2 weeks.

ARM II: Patients receive bevacizumab as patients in arm I and undergo radiation therapy using
intensity-modulated radiation therapy (IMRT), 3-dimensional conformal radiation therapy
(3D-CRT), or proton beam radiation therapy (RT) 5 days a week for 2 weeks.

In both arms, courses repeat every 2 weeks in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for 1 year,
every 6 months for 1 year and then annually thereafter.

Inclusion Criteria:

- Histopathologically proven diagnosis of glioblastoma or variants (gliosarcoma, giant
cell glioblastoma etc); patients will be eligible if the original histology was
lower-grade glioma and a subsequent diagnosis of glioblastoma or gliosarcoma is made

- Patients who did not have recent surgery for their glioblastoma must have shown
unequivocal radiographic evidence for tumor progression by contrast-enhanced magnetic
resonance imaging (MRI) scan (or computed tomography [CT] scan for patients with
non-compatible devices) CT scan within 21 days prior to registration.

* Note: Patients who did have surgery with a post-operative contrast-enhance scan
falling outside the 5 week window prior to registration, must have a repeat MRI scan
(or CT scan for patients with non-compatible devices) within 21 days prior to
registration.

- Patients also must have passed an interval of 6 months or greater between completion
of prior radiotherapy and registration; if patients have not passed an interval of at
least 6 months, they may still be eligible if they meet one or more of the following
criteria:

- New areas of tumor outside the original radiotherapy fields as determined by the
investigator, or

- Histologic confirmation of tumor through biopsy or resection, or

- Nuclear medicine imaging, magnetic resonance (MR) spectroscopy, or MR perfusion
imaging consistent with true progressive disease, rather than radiation necrosis
obtained within 28 days of registration AND an interval of at least 90 days
between completion of radiotherapy and registration

- Patients unable to undergo MR imaging because of non-compatible devices can be
enrolled provided CT scans are obtained and are of sufficient quality; patients
without non-compatible devices may not use CT scans performed to meet this requirement

- Prior history of standard dose CNS radiation of 60 Gy in 30 fractions or 59.4 Gy in
1.8 Gy fractions, or equivalent or lower doses

- Patients who have received prior treatment with non-standard radiation therapy (RT)
dose and fractionation, interstitial brachytherapy, stereotactic radiosurgery, etc.
are eligible

- Patients must have recovered from the toxic effects of prior therapy, and there must
be a minimum time of 28 days prior to registration from the administration of any
investigational agent or prior cytotoxic therapy with the following exceptions:

- 14 days from administration of vincristine

- 42 days from administration of nitrosoureas

- 21 days from administration of procarbazine

- Patients having undergone recent resection of their glioblastoma (within 5 weeks prior
to registration) must have recovered from the effects of surgery; for CNS related core
or needle biopsies, a minimum of 7 days must have elapsed prior to registration

- Residual disease following resection of recurrent glioblastoma is not mandated for
eligibility into the study; to best assess the extent of residual disease
post-operatively, a post-operative or intra-operative MRI scan (or CT scan for
patients with non-compatible devices) must be performed prior to registration and
should be within 96 hours post surgery (although 24 hours would be optimum)

- History/physical examination, including neurologic examination, within 14 days prior
to registration

- Karnofsky performance status >= 60 within 14 days prior to registration

- Complete blood count (CBC)/differential obtained within 14 days prior to registration,
with adequate bone marrow function

- Absolute neutrophil count (ANC) >= 1,500 cells/mm^3

- Platelets >= 75,000 cells/mm^3

- Hemoglobin >= 9.0 g/dl (Note: the use of transfusion or other intervention to achieve
hemoglobin (Hgb) >= 9.0 g/dl is acceptable)

- Total bilirubin =< 2.0 mg/dL

- Serum glutamic oxaloacetic transaminase (SGOT) or aspartate aminotransferase (AST) =<
2.5 times the upper limit of normal

- Serum creatinine =< 1.8 mg/dL

- Urine protein creatinine (UPC) ratio >= 1.0 within 14 days prior to registration OR
urine dipstick for proteinuria >= 2+ (patients discovered to have >= 2+ proteinuria on
dipstick urinalysis at baseline should undergo a 24-hour urine collection and must
demonstrate =< 1g of protein in 24 hours to be eligible)

- Note: UPC ratio of spot urine is an estimation of the 24-hour urine protein
excretion; a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1
gm; UPC ratio is calculated using one of the following formulas:

- [urine protein]/[urine creatinine]: if both protein and creatinine are
reported in mg/dL

- [(urine protein) x 0.088]/[urine creatinine]: if urine creatinine is
reported in mmol/L

- Patients must not be pregnant (positive pregnancy test) or breast feeding; pregnancy
test must be done within 14 days prior to registration; effective contraception (men
and women) must be used in patients of child-bearing potential while on trial and for
6 months after

- Patients on full-dose anticoagulants (e.g., warfarin or low molecular weigh [LMW]
heparin) must meet both of the following criteria:

- No active bleeding or pathological condition that carries a high risk of bleeding
(e.g., tumor involving major vessels or known varices)

- In-range international normalized ratio (INR) (usually between 2 and 3) on a
stable dose of oral anticoagulant or on a stable dose of low molecular weight
heparin, within 14 days prior to registration

- Patient must be able to provide study-specific informed consent prior to study entry

Exclusion Criteria:

- More than three relapses

- Infratentorial or leptomeningeal evidence of recurrent disease

- Recurrent or persistent tumor greater than 6 cm in maximum diameter

- Prior therapy with an inhibitor of vascular endothelial growth factor (VEGF) or VEGFR
(including bevacizumab)

- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for a minimum of 1 year (for example, carcinoma in situ of the breast, oral cavity, or
cervix are all permissible)

- Severe, active co-morbidity, defined as follows:

- Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months prior to registration

- Transmural myocardial infarction within the last 6 months prior to registration

- History of stroke or transient ischemic attack within 6 months prior to
registration

- Significant vascular disease (e.g., aortic aneurysm, history of aortic
dissection) or clinically significant peripheral vascular disease

- Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of registration

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy at the time of registration

- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
note, however, that laboratory tests for liver function other than screening
panel and coagulation parameters are not required for entry into this protocol

- Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease
Control and Prevention (CDC) definition; note, however, that human
immunodeficiency virus (HIV) testing is not required for entry into this
protocol; the need to exclude patients with AIDS from this protocol is necessary
because the treatments involved in this protocol may be significantly
immunosuppressive; protocol specific requirements may also exclude
immuno-compromised patients

- Pregnancy or women of childbearing potential and men who are sexually active and not
willing/able to use medically acceptable forms of contraception; this exclusion is
necessary because the treatment involved in this study may be significantly
teratogenic

- Prior allergic reaction to the study drug (bevacizumab)

- Prior history of hypertensive crisis or hypertensive encephalopathy

- History of a non-healing wound, ulcer, or bone fracture within 90 days (3 months)
prior to registration

- Gastrointestinal bleeding or any other hemorrhage/bleeding event Common Terminology
Criteria for adverse Events (CTCAE), v. 4 grade 3 or greater within 30 days prior to
registration

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to registration (with the exception of craniotomy)
We found this trial at
31
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Scarborough, Maine 04074
Principal Investigator: Ian J. Bristol
Phone: 207-396-8090
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1720 2nd Ave S
Birmingham, Alabama 35233
(205) 934-4011 
Principal Investigator: John B. Fiveash
Phone: 205-934-0309
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301 University Blvd
Galveston, Texas 77555
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Principal Investigator: Martin Colman
Phone: 409-772-1950
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200 North Park Street
Kalamazoo, Michigan 49007
(269) 382-2500
Principal Investigator: Raymond S. Lord
Phone: 269-373-7458
West Michigan Cancer Center In 1994, Borgess Health Alliance and Bronson Healthcare Group opened the...
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60 Crittenden Blvd # 70
Rochester, New York 14642
(585) 275-2121
Principal Investigator: Yuhchyau Chen
Phone: 585-275-5830
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808 North 39th Avenue
Yakima, Washington 98902
Principal Investigator: Sean F. Cleary
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525 E Market St
Akron, Ohio 44304
(330) 375-3000
Principal Investigator: Charles A. Kunos
Phone: 800-641-2422
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Ann Arbor, Michigan 48109
Principal Investigator: Christina I. Tsien
Phone: 800-865-1125
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155 5th St NE
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(330) 615-3000
Principal Investigator: Charles A. Kunos
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171 Ashley Avenue
Charleston, South Carolina 29425
843-792-1414
Principal Investigator: Pierre Giglio
Phone: 843-792-9321
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Fort Wayne, Indiana 46804
Principal Investigator: Brian K. Chang
Phone: 260-373-8888
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835 S Van Buren St
Green Bay, Wisconsin 54301
(920) 433-0111
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1726 Shawano Ave
Green Bay, Wisconsin 54303
(920) 498-4200
Principal Investigator: Gregory M. Cooley
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501 N. Elam Avenue
Greensboro, North Carolina 27403
336-832-1100
Principal Investigator: Matthew A. Manning
Phone: 336-832-0821
Cone Health Cancer Center Located adjacent to Wesley Long Hospital, our Cone Health Cancer Center...
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1301 Punchbowl St
Honolulu, Hawaii 96813
(808) 538-9011
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Phone: 808-545-8548
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Indianapolis, Indiana 46202
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Phone: 317-274-2552
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555 N Duke St
Lancaster, Pennsylvania 17602
(717) 544-5511
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Louisville, Kentucky 40202
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295 Varnum Ave
Lowell, Massachusetts 01854
(978) 937-6000
Principal Investigator: Matthew S. Katz
Phone: 978-788-7084
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3100 Shore Drive
Marinette, Wisconsin 54143
715.735.4200
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Miami, Florida 33136
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New Haven, Connecticut 6520
(203) 432-4771
Principal Investigator: Joseph N. Contessa
Phone: 203-785-5702
Yale University Yale's roots can be traced back to the 1640s, when colonial clergymen led...
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8303 Dodge Street
Omaha, Nebraska 68114
(402) 354–4000
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Philadelphia, Pennsylvania 19103
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Phoenix, Arizona 85013
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Phoenix, Arizona 85027
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Pittsburgh, Pennsylvania 15212
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660 S Euclid Ave
Saint Louis, Missouri 63110
(314) 362-5000
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Phone: 800-600-3606
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
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615 N Michigan St
South Bend, Indiana 46601
(574) 647-1000
Principal Investigator: David A. Hornback
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Sturgeon Bay, Wisconsin 54235
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Walnut Creek, California 94598
Principal Investigator: Daniel M. Chinn
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