Erlotinib and Sirolimus in Treating Patients With Recurrent Malignant Glioma

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring adult giant cell glioblastoma, adult gliosarcoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult mixed glioma, recurrent adult brain tumor, adult glioblastoma, adult pilocytic astrocytoma, adult diffuse astrocytoma, adult subependymal giant cell astrocytoma, adult oligodendroglioma Read More

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