Low Dose Radiation Therapy for Glioblastoma Multiforme
Condition: High Grade Glioma
MeSH terms: Glioblastoma
Intervention: Low Dose Fractionated Radiation Therapy (LDFRT); Temozolomide
Intervention description: All patients will receive 0.5 Gy of radiation therapy twice daily. This study will include a safety run-in component. If > 33% of patients in the initial cohort of 6 experience grade 3 or greater hematologic toxicity according to the NCI Common Toxicity Criteria version 4, then a dose reduction will occur following the schedule listed below.; All patients will receive temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle) for a total of 1 year or until the time of disease progression.
Intervention MeSH terms: Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Recurrent Glioblastoma Multiforme; Recurrent Anaplastic Astrocytoma; Surgery; Adjuvant Radiation; Adjuvant Temozolomide

Summary:

      To evaluate the safety and effectiveness of low dose rate radiation therapy plus
      temozolomide. This will be in patients with High Grade Glioma (to only include Anaplastic
      Astrocytoma or Glioblastoma Multiforme) who have previously been treated with surgery
      followed by radiation surgical resection followed by adjuvant radiation therapy plus
      temozolomide.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have recurrent GBM (Glioblastoma Multiforme)or Anaplastic Astrocytoma.

          -  The diagnosis of GBM or Anaplastic Astrocytoma.

          -  Patients must have been previously treated with surgical resection (any extent okay)
             and adjuvant radiation therapy plus temozolomide.

          -  Patients must be at least 12 months from completion of radiation therapy

          -  At least 2 months from completion of temozolomide (to be consistent with the the
             "rechallenge" group from Perry et al. JCO 2010).

          -  Age >18 years

          -  ECOG performance status <2 (Karnofsky >60%, see appendix A).

          -  There must be measurable disease on MRI.

          -  Patients must have normal organ and marrow function as defined below:

          -  Women must not be pregnant

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Temozolomide re-treatment is planned by the treating neuro-oncologist.

          -  The most recent brain tumor pathology obtained for the patient must be glioblastoma.

        Exclusion Criteria:

          -  Must be able to receive an MRI

          -  Patients may not be receiving any other investigational cancer treatment agents at the
             time of enrollment.

          -  Patients may not have previously failed treatment with salvage temozolomide.

          -  Patients may not have previously failed treatment with a VEGF inhibitor.

          -  Patients may not have previously been treated with >1 course of radiotherapy.

          -  Patients may not have previously been treated with radiosurgery to the brain.

          -  Uncontrolled intercurrent illness

          -  Pregnant and breastfeeding women are excluded. Women of child-bearing potential who
             are unwilling or unable to use and acceptable method of birth control to avoid
             pregnancy for the entire study period and up to 12 weeks after the study are excluded.
             Male subjects must also agree to use effective contraception for the same period as
             above.