Efficacy of Hypofractionated XRT w/Bev. + Temozolomide for Recurrent Gliomas



Status:Active, not recruiting
Conditions:Brain Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:4/17/2018
Start Date:November 2011
End Date:November 2020

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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

This phase II trial studies how well giving hypofractionated radiation therapy together with
temozolomide and bevacizumab works in treating patients with high-grade glioblastoma
multiforme or anaplastic glioma. Specialized radiation therapy, such as hypofractionated
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. Drugs used in chemotherapy, such as
temozolomide, work in different ways to stop the growth of tumor cells, either by killing the
cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can
block tumor growth in different ways. Some block the ability of tumor to grow and spread.
Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving
hypofractionated radiation therapy together with temozolomide and bevacizumab may kill more
tumor cells.

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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).

OUTLINE:

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
toxicity.

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
criteria:

- 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 treatment

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

- 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
participation

- 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
waived
We found this trial at
5
sites
5801 South Ellis Avenue
Chicago, Illinois 60637
 773.702.1234
Principal Investigator: M. K. Nicholas, MD
University of Chicago One of the world's premier academic and research institutions, the University of...
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303 East Superior Street
Chicago, Illinois 60611
Principal Investigator: Jeffrey Raizer, MD
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Lake Forest, Illinois 60045
Principal Investigator: Joseph Imperato, MD
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Lake Forest, IL
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Naperville, Illinois 60540
Principal Investigator: William Broderick, MD
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Naperville, IL
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Warrenville, Illinois 60555
Principal Investigator: Vinai Gondi, MD
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Warrenville, IL
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