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