Everolimus and Whole-Brain Radiation Therapy in Treating Patients With Brain Metastasis From Non-Small Cell Lung Cancer

• Status: Terminated
• Trial end date: 2011-02-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving everolimus together with whole-brain radiation therapy may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus and to see how well it works when given together with whole-brain radiation therapy in treating patients with brain metastasis from non-small cell lung cancer.

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

Details

• Lead Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Everolimus; Sirolimus

Criteria

DISEASE CHARACTERISTICS:

• Radiographically confirmed brain metastases with histopathologically confirmed primary non-small cell lung cancer that will benefit from whole-brain radiotherapy

• Must have ≥ 1 measurable intracranial site of disease, according to RECIST criteria, that has not been previously treated with stereotactic radiation

• Must have stable extracranial disease for 4 weeks

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Life expectancy ≥ 12 weeks

• ANC > 1,500/mm³

• Platelets > 100,000/mm³

• Hemoglobin > 11 g

• BUN ≤ 25 mg

• Serum creatinine < 1.5 times upper limit of normal (ULN)

• Serum bilirubin ≤ 1.5 times ULN

• Serum transaminases ≤ 2 times ULN (< 5 times ULN if patient has liver metastases)

• Cholesterol ≤ 300 mg/dL

• Triglycerides ≤ 2.5 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment

• No other malignancies within the past 3 years, except for adequately treated carcinoma in situ of the cervix or basal or squamous cell carcinomas of the skin

• No severe and/or uncontrolled medical conditions or other conditions that could affect participation in the study, including any of the following:

• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within the past 6 months, or serious uncontrolled cardiac arrhythmia

• Severely impaired lung function (i.e., FEV1 < 0.8 cc)

• Uncontrolled diabetes as defined by fasting serum glucose ≥ 1.5 times ULN

• Any active (acute or chronic) or uncontrolled infection/disorders

• Non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy

• Liver disease, such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis

• No known history of HIV seropositivity

• No impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)

• No active, bleeding diathesis

• No known hypersensitivity to everolimus or other rapamycin (i.e., sirolimus, temsirolimus) or to its excipients

• No history of noncompliance to medical regimens

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from the acute toxicities of any prior therapy

• Prior surgical resection of a brain metastasis allowed

• The extent of surgical resection in patients having prior resection of 1 of multiple metastases shall be documented as a biopsy, subtotal resection, or total resection as described by the operative report and/or post-operative imaging

• At least 3 weeks since prior major surgery or completion of extracranial radiation

• At least 3 weeks since prior and no concurrent systemic anticancer therapy, other than the study medications administered as part of this study protocol

• At least 6 weeks since prior nitrosoureas

• More than 1 week since prior and no concurrent immunization with attenuated live vaccines

• More than 3 weeks since prior chemotherapy

• No prior brain radiotherapy of any form

• No concurrent chronic treatment with systemic steroids or other immunosuppressive agents, except steroids for neurological stability following the diagnosis of brain metastases

• No prior treatment with an mTOR inhibitor

• No concurrent anti-vitamin K medication, except low dose coumarin

• No concurrent drugs or substances known to be inhibitors or inducers of the isoenzyme CYP3A

• No other concurrent investigational therapy