RATIONALE: Cilengitide may stop the growth of brain metastases by blocking blood flow to the tumor. Radiation therapy uses high energy X-rays to kill tumor cells. Giving cilengitide together with radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of cilengitide when given together with whole-brain radiation therapy in treating patients with brain metastases from lung cancer.

OBJECTIVES:

• Primary

  • To assess the safety and tolerability of daily cilengitide by determining its dose-limiting toxicity and maximum-tolerated dose when combined with concomitant fractionated whole-brain radiation therapy in patients with brain metastases from lung cancer.

• Secondary

  • To collect evidence of the best overall response rate, overall survival, brain-specific progression-free survival, and tumor-specific progression-free survival of these patients.
  • To collect evidence of changes in functional MRI imaging studies at 6 and 12 weeks after initiation of therapy.
  • To collect evidence of early response by functional MRI (ASL technique) on days 1, 4, and 12, immediately before and after the administration of cilengitide.
  • To collect evidence of changes in neurological and neurocognitive function tests at 6 and 12 weeks after initiation of therapy.
  • To further evaluate the safety and toxicity of the combination of cilengitide and whole-brain radiation therapy.
  • To further evaluate the pharmacokinetics of cilengitide administered daily.

OUTLINE:

Patients receive oral cilengitide once daily and undergo whole-brain radiotherapy on the same days. Treatment continues for 2 weeks in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection on days 1, 4, 5, and 12 for pharmacokinetic studies.

After completion of study treatment, patients are followed for 10 weeks.

Inclusion Criteria:

DISEASE CHARACTERISTICS:

• Histologically confirmed lung cancer (small cell or non-small cell lung cancer)
• Patient must be eligible for whole-brain radiotherapy
• Presence of brain metastasis (single or multiple, synchronous or metachronous) from lung cancer not amenable to surgery or radiosurgery (presence of metastases at any other site is allowed)
• No leptomeningeal metastasis or known subarachnoid spread of tumor

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-1 (ECOG PS 2 allowed if due to the presence of cerebral metastases and not due to a high peripheral-tumor load or other reasons)
• Life expectancy ≥ 3 months
• Adequate hematologic function
• Total bilirubin < 1.5 times upper limit of normal (ULN)
• AST, ALT, and alkaline phosphatase < 2.5 times ULN
• Creatinine clearance > 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after completion of study treatment
• No history of acute or chronic renal disease
• No other malignancies treated within the past 5 years, except adequately treated carcinoma in situ of the cervix or basal cell carcinoma of the skin
• No uncontrolled hypertension
• No history of coagulation disorder associated with bleeding or recurrent thrombotic events
• No peptic ulcer disease within the past 6 months
• No congestive heart failure, high risk for uncontrolled arrhythmia, or history of clinically significant coronary heart disease
• No known alcohol or drug abuse
• No other significant or acute concomitant disease
• No dementia or altered mental status

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Concurrent corticosteroids allowed if the dosing regimen has ben stable ≥ 5 days
• Concurrent anticonvulsants allowed if the dosing regimen has been stable for the past week
• More than 30 days since prior participation in another clinical trial
• No concurrent anticoagulation with vitamin K antagonists, therapeutic-dose anticoagulation with heparin resulting in prolonged PTT, or therapeutic-dose anticoagulation with low molecular weight heparin (low-dose [i.e. prophylactic], low molecular weight heparins allowed)
• No prior whole-brain radiation or radiosurgery
• No prior antiangiogenic therapy
• No other concurrent anticancer therapy