High Dose Gefitinib for the Treatment of Carcinomatous Meningitis in Adult Patients With Non-Small Cell Lung Cancer and Known or Suspected EGFR Mutations

- The standard therapy for this type of cancer is to give chemotherapy directly into the
spinal fluid, usually by a spinal tap. Some chemotherapy may, in some cases, be combined
with radiation. This study looks at a different way of treating this type of cancer.

- This study is specifically for patients whose lung cancer has changes in a protein
called the epidermal growth factor receptor (EGFR). The study drug, gefitinib, was
developed to stop the signals from the EGFR that tell certain types of lung cancers
tumors to grow. By using higher doses than are normally used, we hope to increase the
amount of drug in the spinal fluid to attempt to kill the cancer cells around the spinal
cord and brain.

- Since we are looking for the highest dose of gefitinib that can be given safely, not
everyone who participates in this study will be receiving the same amount of drug.

- Patients will start taking gefitinib daily by mouth on Day 1 and will continue taking
this medication daily at home. On the first day the patient takes gefitinib and on Day
14 of each treatment cycle (1 cycle equals 28 days), the patient will undergo: Physical
examination by the study doctor and a detailed neurological exam by a neuro-oncologist;
sampling of cerebrospinal fluid (CSF) by lumbar puncture; review of current medications;
measurement of vital signs; check on the patients ability to perform daily activities;
blood work.

- If the patient is tolerating the study medication well, then the patient will receive a
lower dose for days 15-28 of the cycle.

- At the end of each cycle on Day 28, the patient will meet with the study doctor and have
the following: a physical examination; review of current medications; measurement of
vital signs, check on the patients ability to perform daily activities; blood tests; MRI
of the brain and spinal cord to assess tumor response; every two cycles a CT scan of the
chest and abdomen to assess the tumor response.

Inclusion Criteria:

- Histologically or cytologically proven diagnosis of non-small cell lung cancer of any
histologic subtype

- High likelihood of gefitinib sensitivity, as evidenced by one or more of the
following: previous complete or partial response to treatment with an epidermal growth
factor receptor-tyrosine kinase inhibitor, erlotinib, or gefitinib; known somatic
mutation of the EGFR tyrosine kinase

- Recurrent or persistent disease as manifested by carcinomatous meningitis

- ECOG PS 0-3

- Age 18 years or older

- Greater than 2 weeks since prior radiation therapy

- Greater than 3 weeks since prior major surgery

- Adequate hematologic, renal, and/or hepatic function

- Coagulation parameters: international normalized ratio(INR)less than or equal to 1.5
and an activated thromboplastin time < 50 seconds

Exclusion Criteria:

- Previous Grade 4 toxicity on gefitinib or erlotinib leading to dose reduction or
interruption

- Uncontrolled brain metastases, or brain metastases associated with mass effect that
would contraindicate lumbar puncture

- Any other malignancy within the past five years, except for adequately treated
carcinoma of the cervix, basal or squamous cell carcinomas of the skin

- Dysphagia

- Active gastrointestinal disease or disorder that alters gastrointestinal motility or
absorption

- Incomplete healing from previous oncologic or other major surgery

- Any pre-existing severe or unstable medical condition

- Any condition requiring concurrent and ongoing use of anticoagulation

- Inability to undergo collection of CSF, either by repeated lumbar puncture or
placement of an Omaya reservoir

- Pregnant or breastfeeding

- Concurrent intrathecal drug administration or radiotherapy

- Concurrent systemic chemotherapy or investigational agent

- Anticoagulant except aspirin or heparin flushes

- Enzyme-inducing anti-epileptic drug

- CYP3A4 inhibitors