Erlotinib and Sirolimus in Treating Patients With Recurrent Malignant Glioma

• Status: Completed
• Trial end date: 2012-09-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Erlotinib and sirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I/II trial is studying the side effects and best dose of erlotinib when given together with sirolimus and to see how well they work in treating patients with recurrent malignant glioma.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Jonsson Comprehensive Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Erlotinib Hydrochloride; Everolimus; Sirolimus

Criteria

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