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

This is an interventional treatment trial for Lung Cancer focused on measuring tumors metastatic to brain, recurrent non-small cell lung cancer, stage IV non-small cell lung cancer Read More

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