Pulse Reduced Dose-Rate Radiation Therapy and Bevacizumab in Treating Patients with Recurrent Glioblastoma or Anaplastic Glioma Previously Treated with Radiation Therapy, Temozolomide, and / or Bevacizumab

Status: Active

Description

This phase II trial studies how well pulse reduced dose-rate (PRDR) radiation therapy and bevacizumab work in treating patients with glioblastoma or anaplastic glioma that has come back after treatment with radiation therapy, temozolomide, and / or bevacizumab. PRDR radiation therapy uses high energy x-rays to kill tumor cells but at a much slower rate and may be effective in inducing tumor regression. Monoclonal antibodies, such as bevacizumab, may block tumor growth in different ways by targeting certain cells. Giving PRDR radiation therapy and bevacizumab may be effective in treating patients with recurrent glioblastoma or anaplastic glioma.

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-naive – 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; patients with prior vascular endothelial growth factor (VEGF) inhibitor exposure will be placed in the bevacizumab exposed group (groups 2 and 4); prior treatment with Gliadel is permitted for all groups
  • Prior radiation requirements * For bevacizumab-naive patients (groups 1 and 3) a minimum of 6 months must have elapsed since completion of initial radiation therapy for study entry, and there is no minimum time since completion of last chemotherapy * For bevacizumab-exposed patients (groups 2 and 4) minimum of 3 months must have elapsed since completion of initial radiation therapy and there is no minimum time since completion of last chemotherapy
  • Patients must have a KPS performance status of >= 60
  • Hemoglobin >= 10 (within 14 days prior to initiation of study treatment)
  • Platelets >= 100,000/mm^3 (within 14 days prior to initiation of study treatment)
  • Absolute neutrophil count >= 1500/mm^3 (within 14 days prior to initiation of study treatment)
  • Bilirubin =< 1.5 x upper limit of normal range (within 14 days prior to initiation of study treatment)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x upper limit of normal range (within 14 days prior to initiation of study treatment)
  • Blood urea nitrogen (BUN) =< 1.5 x upper limit of normal range (within 14 days prior to initiation of study treatment)
  • Creatinine =< 1.5 x upper limit of normal range (within 14 days prior to initiation of study treatment)
  • Urine protein via dipstick =< 2+ or =< 100 mg/dl (within 14 days prior to initiation of study treatment)
  • International normalized ratio (INR) =< 1.5 and partial thromboplastin time (PPT) =< 5 seconds above the upper limit of normal (ULN)
  • 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 the University of Wisconsin (UW) must have their pathology slides sent to the UW 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 may NOT be on full dose anti-coagulation therapy; maintenance doses of low molecular weight heparin is permissible
  • Patients with a prior malignancy will NOT be eligible for participation aside from the following exception: * Patients who have had any curatively treated invasive 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

Locations & Contacts

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: Active
Contact: H. Ian Robins
Phone: 877-405-6866
Email: hirobins@wisc.edu
Wausau
Aspirus Regional Cancer Center
Status: Active
Contact: Christopher S. Platta
Phone: 715-847-2866
Email: christopher.platta@aspirus.org
Wisconsin Rapids
Aspirus UW Cancer Center
Status: Active
Contact: Ronnie James Kirschling
Phone: 715-421-4442
Email: ron.kirschling@aspirus.org

Trial Objectives and Outline

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

I. Determine the safety profile of this regimen.

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

III. Qualitatively compare the results of brain autopsy in patients who have received PRDR-radiation therapy (RT)/bevacizumab to prior results (n=15) obtained with PRDR-RT.

IV. Determine the impact of this regimen on neurologic symptoms via Functional Assessment of Cancer Therapy-Breast Cancer (FACT-Br) and FACT-Fatigue scales and Karnofsky performance status (KPS).

OUTLINE:

CONCURRENT PHASE: Patients undergo PRDR-RT five days a week for 5.5 weeks and receive bevacizumab intravenously (IV) over 30-90 minutes once between days -3 and 0 and then once every 2 weeks for 5 doses during re-irradiation therapy. Patients who have been exposed to bevacizumab prior to study entry receive bevacizumab IV over 30-90 minutes every 4 weeks for only 2-3 courses.

ADJUVANT PHASE: Patients receive bevacizumab IV over 30-90 minutes every 2 or 3 weeks. Courses repeat every 4-6 weeks in the absence of disease progression or unacceptable toxicity.

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

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Wisconsin Hospital and Clinics

Principal Investigator
H. Ian Robins

Trial IDs

Primary ID CO11374
Secondary IDs NCI-2012-02775, 2012-0648
Clinicaltrials.gov ID NCT01743950