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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor

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Trial Information

RANDOMIZED PHASE II TRIAL OF CONCURRENT BEVACIZUMAB AND RE-IRRADIATION VERSUS BEVACIZUMAB ALONE AS TREATMENT FOR 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 14 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 30 days
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 MRI scan (or CT scan for patients with
non-compatible devices) must be performed within 30 days 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 >= 70 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 >= 100,000 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

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

Exclusion Criteria:

- More than two relapses

- Multifocal, infratentorial, or leptomeningeal evidence of recurrent disease

- Recurrent or persistent tumor greater than 5 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)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall survival

Outcome Description:

Estimated using the Kaplan-Meier method (Kaplan 1958), and differences between treatment arms will be tested in the log-rank test (Mantel 1966).

Outcome Time Frame:

From randomization to the date of death or the last follow-up. Analysis occurs after XX deaths have bee reported.

Safety Issue:

No

Principal Investigator

Christina Tsien

Investigator Role:

Principal Investigator

Investigator Affiliation:

Radiation Therapy Oncology Group

Authority:

United States: Institutional Review Board

Study ID:

RTOG-1205

NCT ID:

NCT01730950

Start Date:

December 2012

Completion Date:

Related Keywords:

  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Recurrent Adult Brain Tumor
  • Brain Neoplasms
  • Glioblastoma
  • Gliosarcoma

Name

Location

Washington University School of MedicineSaint Louis, Missouri  63110
Medical University of South CarolinaCharleston, South Carolina  29425-0721
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Memorial Hospital of South BendSouth Bend, Indiana  46601
University of Texas Medical BranchGalveston, Texas  77555-1329
John Muir Medical CenterWalnut Creek, California  94598
North Star Lodge Cancer Center at Yakima Valley Memorial HospitalYakima, Washington  98902
Lancaster General HospitalLancaster, Pennsylvania  17604-3555
Allegheny Cancer Center at Allegheny General HospitalPittsburgh, Pennsylvania  15212
Arizona Oncology Services FoundationPhoenix, Arizona  85013
Lowell General HospitalLowell, Massachusetts  01854
Queen's Medical CenterHonolulu, Hawaii  96813
University of Alabama at BirminghamBirmingham, Alabama  35294-3300
Nebraska Methodist HospitalOmaha, Nebraska  68114
University of RochesterRochester, New York  14642
Yale UniversityNew Haven, Connecticut  06520
Radiation Therapy Oncology GroupPhiladelphia, Pennsylvania  19107
Summa Barberton HospitalBarberton, Ohio  44203
Saint Vincent HospitalGreen Bay, Wisconsin  54301
Saint Mary's HospitalGreen Bay, Wisconsin  54303
Bay Area Medical CenterMarinette, Wisconsin  54143
Maine Medical Center- Scarborough CampusScarborough, Maine  04074
University of Michigan University HospitalAnn Arbor, Michigan  48109
University of Miami Miller School of Medicine-Sylvester Cancer CenterMiami, Florida  33136
Norton Health Care Pavilion - DowntownLouisville, Kentucky  40202
Radiation Oncology Associates PCFort Wayne, Indiana  46804
Summa Akron City HospitalAkron, Ohio  44304
Door County Cancer CenterSturgeon Bay, Wisconsin  54235-1495
Cone Health Cancer CenterGreensboro, North Carolina  
IU Health Methodist HospitalIndianapolis, Indiana  46202
Arizona Oncology-Deer Valley CenterPhoenix, Arizona  85027