Erlotinib and Sirolimus in Treating Patients With Recurrent Malignant Glioma

Inclusion Criteria:

* Histologically confirmed malignant glioma, including any of the following:
* Glioblastoma multiforme (GBM)
* Gliosarcoma (GS)
* Anaplastic astrocytoma (AA)
* Anaplastic oligodendroglioma (AO)
* Anaplastic mixed oligoastrocytomas (AMA)
* Malignant astrocytoma not otherwise specified (NOS)
* Prior low-grade glioma allowed provided there is histologic evidence of progression to a malignant glioma
* Must meet the following criteria for phase I:
* All types of malignant gliomas allowed
* No limitations on the number of relapses
* Must meet the following criteria for phase II:
* Only patients with GBM or GS are allowed
* Must be in first, second, or third relapse
* patients who had prior therapy (must include external beam radiotherapy) for a low-grade glioma that is considered standard, non-surgical treatment for a high-grade glioma, the surgical diagnosis of high-grade glioma will be considered the first relapse
* Must have shown unequivocal radiographic evidence for tumor progression by MRI or CT scan and have either measurable or evaluable disease
* Measurable disease is defined as bidimensionally measurable lesions with clearly defined margins by MRI scan
* Evaluable disease is defined as unidimensionally measurable lesions or masses with margins not clearly defined
* Karnofsky performance status ≥ 60%
* Life expectancy \> 8 weeks
* Absolute neutrophil count ≥ 1,500/μL
* Platelets ≥ 100,000/μL
* Total bilirubin \< 2.0 x upper limit of institutional normal (ULN)
* AST \< 2.0 x ULN
* Creatinine \< 1.5 x ULN
* Fasting serum triglycerides \< 2.5 x ULN
* Fasting serum cholesterol \< 350 mg/dL
* Women of child-bearing potential and men must agree to use adequate contraception (i.e., hormonal or barrier method of birth control) prior to study entry and for the duration of study participation
* Recovered from all toxicities associated with prior surgery, radiotherapy, or chemotherapy
* At least 1 week since prior surgery
* At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
* At least 12 weeks since prior radiation therapy
* Must not receive any P450-enzyme-inducing anticonvulsants (EIAC) for at least 2 weeks prior to and during participation in this trial

Exclusion Criteria:

* Women who are pregnant or lactating
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib hydrochloride or sirolimus
* Uncontrolled intercurrent illness including, but not limited to, any of the following:
* Ongoing or active infection requiring IV antibiotics
* Symptomatic congestive heart failure
* Unstable angina pectoris
* Cardiac arrhythmia
* Hyperlipidemia (e.g., grade 3 or greater hypercholesterolemia or hypertriglyceridemia) not controlled with medication
* Psychiatric illness or social situations that would limit compliance with study requirements
* Disorders associated with significant immunocompromise (e.g., HIV or systemic lupus erythematosus \[SLE\])
* Patients with another primary malignancy that has required treatment other than surgery within the past year (except for nonmelanoma skin cancer or carcinoma in situ)
* Patients with the inability to comply with the protocol requirements in the opinion of the investigator including those who can not take oral medications
* Patients who are unable to undergo routine imaging evaluations with magnetic resonance imaging scans
* Prior EGFR-directed or mTOR-directed therapies including sirolimus or sirolimus analogs
* Patients taking concurrent immunosuppressive agents other than prescribed corticosteroids
* Concurrent antineoplastic or antitumor agents that are not part of the study therapy including chemotherapy, radiation therapy, immunotherapy, and hormonal anticancer therapy
* Blood products during cycle 1 unless a patient experiences hematologic DLT or if it is medically imperative to administer a transfusion
* Concurrent grapefruit or grapefruit juice
* Other concurrent investigational agents
* Receiving concurrent enzyme-inducing antiepileptic drugs