A phase II trial of low dose fractionated radiation therapy as a chemo-potentiator of salvage temozolomide for recurrent anaplastic astrocytoma and glioblastoma multiforme
Johns Hopkins Kimmel Cancer Center in Baltimore
Sibley Memorial Hospital
To evaluate the safety and effectiveness of low dose rate radiation therapy plus temozolomide. This will be in patients with recurrent anaplastic astrocytoma or glioblastoma Multiforme who have previously been treated with surgery followed by radiation surgical resection followed by adjuvant radiation therapy plus temozolomide.
Inclusion Criteria:ï¿½Patients must have recurrent AA/GBM.ï¿½The diagnosis of AA/GBMï¿½At the time of initial diagnosis, patients must have been treated with surgical resection followed by adjuvant radiation therapy plus temozolomideï¿½Patients must be at least 12 months from completion of radiation therapyï¿½At least 2 months from completion of adjuvant temozolomide.ï¿½Age greater than 18 yearsï¿½ECOG performance status less than 2 (Karnofsky greater than 60%, see appendix A).ï¿½There must be measurable disease on MRI.ï¿½Patients must have normal organ and marrow function as defined below:ï¿½Women must not be pregnantï¿½Ability to understand and the willingness to sign a written informed consent documentï¿½Temozolomide re-treatment is planned by the treating neuro-oncologist.ï¿½The most recent brain tumor pathology obtained for the patient must be glioblastoma.Exclusion Criteria:ï¿½Must be able to receive an MRIï¿½Patients may not be receiving any other investigational cancer treatment agents at the time of enrollment.ï¿½Patients may not have previously failed treatment with salvage temozolomide.ï¿½Patients may not have previously failed treatment with a VEGF inhibitor.ï¿½Patients may not have previously been treated with greater than 1 course of radiotherapy.ï¿½Patients may not have previously been treated with radiosurgery to the brain.ï¿½Uncontrolled intercurrent illnessï¿½Pregnant 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.
Radiation: Low Dose Fractionated Radiation Therapy (LDFRT)All patients will receive 0.5 Gy of radiation therapy twice daily. This study will include a safety run-in component. If greater than 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. Otherwise, following a 1 month waiting period after the first cycle of adjuvant LDFRT plus temozolomide for the first cohort of patients, the phase 2 study will open for full accrual. Patients will receive radiation with the first six 28-day cycles of temozolomide.Drug: TemozolomideAll 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.
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