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A Phase II Study of the Efficacy of Hypofractionated Radiation Therapy With Bevacizumab and Temozolomide Followed by Maintenance Temozolomide and Bevacizumab for Recurrent High-Grade Gliomas

Phase 2
18 Years
Open (Enrolling)
Adult Anaplastic Astrocytoma, Adult Anaplastic Ependymoma, Adult Anaplastic Oligodendroglioma, Adult Giant Cell Glioblastoma, Adult Glioblastoma

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Trial Information

A Phase II Study of the Efficacy of Hypofractionated Radiation Therapy With Bevacizumab and Temozolomide Followed by Maintenance Temozolomide and Bevacizumab for Recurrent High-Grade Gliomas


I. To determine the overall survival (OS) for patients with recurrent high grade malignant
gliomas treated with concurrent radiation, temozolomide, and bevacizumab followed by
adjuvant temozolomide and bevacizumab.


I. Determine the impact of this regimen on neurologic symptoms via Functional Assessment of
Cancer Therapy-Brain (FACT-Br) and FACT-Fatigue scales and Eastern Cooperative Oncology
Group (ECOG) performance status.

II. Determine the safety profile of this regimen. III. Determine the progression free
survival (PFS) at 6 and 12 months (all patients) as well as at 3 months (bevacizumab-exposed
patients only).


CONCURRENT THERAPY: Patients undergo hypofractionated radiation therapy 5 days a week
beginning on day 0. Patients also receive temozolomide orally (PO) once daily (QD) and
bevacizumab intravenously (IV) over 30-90 minutes once every 2 weeks beginning on days -3 to
0. Treatment continues for 5 weeks in the absence of disease progression or unacceptable

ADJUVANT THERAPY: Beginning 2 weeks after completion of radiation therapy, patients receive
temozolomide PO QD for 6 weeks and bevacizumab IV over 30-90 minutes once every 2 weeks.
Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2-3 months.

Inclusion Criteria:

- Patients must have histologically confirmed diagnosis of glioblastoma multiforme
(GBM) or anaplastic glioma, World Health Organization (WHO) grade 3 or 4

- Patients must have measurable or non-measurable (evaluable) disease recurrence

- Recurrence must be documented based on a combination of clinical and imaging
parameters, consistent with routine clinical practice, with or without
histologic confirmation

- Patients may have had any number of relapses and be eligible for the study

- Patients must have been previously treated with radiation therapy and
temozolomide (bevacizumab-naïve - Groups 1 and 3) or radiation therapy,
temozolomide and bevacizumab (bevacizumab-exposed -Groups 2 and 4); therapy with
these agents may be given together or sequentially in the past

- All patients may have had prior surgery, chemotherapy, and radiation therapy;
prior biologic therapy is permitted only for bevacizumab-exposed patients
(Groups 2 and 4); prior treatment with Gliadel is permitted for all groups

- For bevacizumab-naïve patients (Groups 1 and 3) a minimum of 6 months must have
elapsed since completion of radiation therapy for study entry, and there is no
minimum time since completion of last chemotherapy; for bevacizumab-exposed
patients (Groups 2 and 4) no minimum time since completion of last radiation
therapy, biologic agents, or chemotherapy will be required for study entry

- Patients must have an ECOG performance status of =< 2

- Hemoglobin >= 10

- Platelets >= 100,000/mm^3

- Absolute neutrophil count >= 1500/mm^3

- Bilirubin =< 1.5 x upper limit of normal range (ULN)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN

- Blood urea nitrogen (BUN) =< 1.5 x ULN

- Creatinine =< 1.5 x ULN

- Urine protein/creatinine ratio should be =< 1

- Patients' baseline blood pressure must be adequately controlled with or without
antihypertensive medications prior to enrollment (systolic < 140 mmHg, diastolic
< 90 mmHg)

- Patients must have a baseline evaluation including history and physical
examination with neurological evaluation and magnetic resonance imaging (MRI) of
the brain (with and without gadolinium-based contrast), all completed within 30
days prior to initiation of treatment

- Female patients of child-bearing potential must have a negative pregnancy test
within 14 days prior to enrollment on study; child-bearing potential is defined
as any female (regardless of sexual orientation, having undergone a tubal
ligation, or remaining celibate by choice) who meets one of the following

- Has not undergone a hysterectomy or bilateral oophorectomy

- Or has not been naturally postmenopausal for at least 12 consecutive months
(i.e. has had menses at any time in the preceding consecutive 12 months)

- Females of child-bearing potential and sexually-active males must consent to
follow acceptable birth control methods to avoid contraception while on

- All subjects must have given signed, informed consent prior to registration on

- Patients previously treated outside of Northwestern must have their pathology
slides sent to Northwestern for review and confirmation - NOTE: a copy of the
pathology report is sufficient for registration

Exclusion Criteria:

- • Patients who are pregnant or breast-feeding will NOT be eligible for participation

• Patients with a prior malignancy will NOT be eligible for participation aside from
the following exception:

- Patients who have had any curatively treated malignancy and have been disease free
without treatment for 1 year prior to study entry ARE eligible for participation

- Patients with an active second malignancy (other than non-melanoma skin cancer
or cervical cancer in situ) are NOT eligible for participation

- Patients with uncontrolled hypertension (>= 140/90 mmHg) are NOT eligible for

- Patients who exhibit any other serious concurrent infection or other medical
illness which would jeopardize their ability to receive the therapy outlined in
this protocol with reasonable safety will NOT be eligible for participation

- The eligibility criteria listed above are interpreted literally and cannot be

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:


Outcome Description:

Data will be analyzed using Kaplan-Meier curves. Defined as the time from first re-irradiation treatment until death from any cause.

Outcome Time Frame:

Every 2 months or up to 90 days

Safety Issue:


Principal Investigator

Jeffrey Raizer, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Northwestern University


United States: Institutional Review Board

Study ID:

NU 11C02



Start Date:

November 2011

Completion Date:

November 2014

Related Keywords:

  • Adult Anaplastic Astrocytoma
  • Adult Anaplastic Ependymoma
  • Adult Anaplastic Oligodendroglioma
  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Information Not Provided
  • Astrocytoma
  • Ependymoma
  • Glioblastoma
  • Oligodendroglioma



Northwestern UniversityChicago, Illinois  60611
University of ChicagoChicago, Illinois  60637
Edward Cancer CenterNaperville, Illinois  60540
Central DuPage HospitalWinfield, Illinois  60190
Northwestern Lake Forest HospitalLake Forest, Illinois  60045