A phase II trial of low dose fractionated radiation therapy as a chemo-potentiator of salvage temozolomide for recurrent glioblastoma multiforme
To evaluate the safety and effectiveness of low dose rate radiation therapy plus temozolomide. This will be in patients with recurrent glioblastoma Multiforme who have previously been treated with surgery followed by radiation surgical resection followed by adjuvant radiation therapy plus temozolomide.
Inclusion Criteria: â?¢Patients must have recurrent GBM. â?¢The diagnosis of GBM â?¢At the time of initial diagnosis, patients must have been treated with surgical resection followed by adjuvant radiation therapy plus temozolomide â?¢Patients must be at least 12 months from completion of radiation therapy â?¢At least 9 months from completion of adjuvant temozolomide. â?¢Age greater than 18 years â?¢ECOG performance status less than 2 (Karnofsky greater than 60%, see appendix A). â?¢There must be measurable disease on MRI. â?¢Patients must have normal organ and marrow function as defined below: â?¢Women must not be pregnant â?¢Ability to understand and the willingness to sign a written informed consent document â?¢Temozolomide re-treatment is planned by the treating neuro-oncologist. â?¢The most recent brain tumor pathology obtained for the patient must be glioblastoma. Exclusion Criteria: â?¢Must be able to receive an MRI â?¢Patients may not be receiving any other investigational cancer treatment agents at the time of enrollment. â?¢Patients may not have previously failed treatment with salvage temozolomide. â?¢Patients may not have previously failed treatment with a VEGF inhibitor. â?¢Patients may not have previously been treated with greater than 1 course of radiotherapy. â?¢Patients may not have previously been treated with radiosurgery to the brain. â?¢Uncontrolled intercurrent illness â?¢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.
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: Temozolomide 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.
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