Ph II Erlotinib + Sirolimus for Pts w Recurrent Malignant Glioma Multiforme

Inclusion Criteria

• Pts have confirmed diagnosis of recurrent primary WHO grade IV malignant glioma (MG). Pts w recurrent disease whose diagnostic pathology confirmed GBM will not need re-biopsy. Pts w prior low-gr glioma / anaplastic glioma are eligible if histologic assessment demonstrates transformation to GBM
• Age >18 yrs
• Interval of >2 wk between prior surgical resection
• Interval of >12 wks between prior external-beam radiation therapy (XRT) unless there is either: histopathologic confirmation of recurrent tumor; new enhancement on MRI outside of XRT treatment field; / progressive radiographic changes after XRT/temo as well as after adjuvant, post-XRT temo
• Interval of >4 wks between chemo & enrollment on protocol unless: unequivocal evidence of tumor progression; & pt has recovered fully from all toxicity associated w prior surgery, XRT/chemo. Pts treated w chemo agents such as VP-16 who would normally be retreated after shorter intervals may be treated at usual starting time even if = 70 percent
• Hematocrit >29 percent, absolute neutrophil count (ANC) >1,500 cells/microliter, platelets >100,000 cells/microliter
• Serum creatinine 7 days prior to baseline Gd-MRI of brain if medically appropriate
• Pts in enzyme inducing antiepileptic drug cohort must be on stable dose of p450-inducing EIAED for >2 wks. Pts in non-EIAED cohort must not receive any p450-EIAED for >2 wks prior to & during participation in trial
• Signed informed consent approved by Institutional Review Board (IRB) prior to pt entry
• If sexually active, pts will take contraceptive measures for duration of treatments & for 3 months following discontinuation of Erlotinib
• Pts who have had prior bevacizumab are eligible however interval of >6 weeks must have elapsed since their last dose

Exclusion Criteria

• Prior mammalian target of rapamycin (mTOR) directed therapy
• Prior epidermal growth factor receptor (EGFR)-directed therapy
• Female pts are pregnant/breast feeding, or adults of reproductive potential not employing effective method of birth control. Women of childbearing potential must have negative serum pregnancy test <72 hours prior to administration of Erlotinib
• Co-medication that may interfere w study results
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, hyperlipidemia not controlled w medication, psychiatric illness/social situations that would limit compliance w study requirements,/disorders associated w significant immunocompromise
• Acute/chronic liver disease
• Impairment of GI function/GI disease that may significantly alter absorption of Erlotinib
• Pts who have received investigational drugs <4 wks prior to entry on study or who have not recovered from toxic effects of such therapy
• Pts who have received biologic, immunotherapeutic/cytostatic agents <1 wk prior to entry on study/have not recovered from toxic effects of such therapy
• Pt is <5 yrs free of another primary malignancy except: if other primary malignancy is not currently clinically significant/requiring active intervention,/if other primary malignancy is basal cell skin cancer/cervical carcinoma in situ. Existence of any other malignant disease is not allowed
• Pts have had any surgery other than resection of brain tumor <2 wks prior to entry on study/have not recovered from side effects of such therapy
• Pts unwilling to/unable to comply w protocol
• Pts w acute/chronic renal insufficiency/those w acute renal insufficiency of any severity due to hepato-renal syndrome/in peri-operative liver transplantation period