Efficacy of Hypofractionated XRT w/Bev. + Temozolomide for Recurrent Gliomas
Condition: Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma
MeSH terms: Glioblastoma; Astrocytoma; Ependymoma; Oligodendroglioma
Intervention: Temozolomide; hypofractionated radiation therapy; bevacizumab; questionnaire administration
Intervention description: Given PO; Undergo hypofractionated radiation therapy; Given IV; Ancillary studies
Intervention MeSH terms: Bevacizumab; Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Information Not Provided

Summary:

      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.
    

Eligibility criteria:

        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