The purpose of this study is to test the safety of different ways of taking erlotinib. The
investigators want to find out what effects, good and/or bad, combination daily low dose and
twice weekly high dose erlotinib has on the patient and lung cancer. The investigators are
also seeing whether different schedules of erlotinib are better at treating lung cancer that
has spread to the central nervous system.
CNS expansion phase:
The pulse continuous regimen will be then assess in patients with EGFR mutant lung cancers
and CNS involvement. An additional expansion cohort (A) will enroll 19 patients with newly
diagnosed EGFR mutant lung cancer with CNS involvement at diagnosis. The patients in the
expansion cohorts will undergo the same treatment plan as the patients in the dose expansion
cohort. A patient in the expansion cohorts will not be replaced if he/she does not finish
the first 28 day (cycle 1) treatment period.
- MSKCC pathologically-proven diagnosis locally advanced Stage III not amenable to
definitive, curative treatment or Stage IV or recurrent non-small cell lung cancer
- Documented presence of EGFR mutation confirmed by MSKCC or a local facility.
- No prior treatment with erlotinib, gefitinib, or other EGFR tyrosine kinase
- Age 18 years
- Measurable (RECIST 1.1) indicator lesion not previously irradiated.
- Karnofsky Performance Status 70%
- Ability to take oral medications
- A negative serum pregnancy test obtained within 4 weeks prior to the start of
treatment in all women of child-bearing potential.
- All women of child bearing potential and sexually active men must agree to use
adequate methods of birth control throughout the study which includes use of oral
contraceptives with an additional barrier methods, double barrier methods,
Depo-Provera, permanent sterilization of patient or partner or total abstinence.
- brain metastases or leptomeningeal not previously treated with radiation or surgery
- Inadequate recovery from any toxicity related to prior treatment (to Grade 2 or
- Inadequate hematologic function defined as ANC < 1000 cells/mm, Platelet count
<75,000/mm or Hemoglobin <9.0g/dL.
- Inadequate hepatic function defined by AST/ALT >3x upper limit of normal (ULN), Total
bilirubin>2x ULN, Alkaline phosphatase >3x ULN.
- Symptomatic brain metastasis requiring radiation therapy or escalating doses of
- Patients with clinically stable brain metastases or leptomeningeal disease
(previously treated or untreated) are eligible. Patients in expansion cohort A must
have at least one untreated CNS lesion
- Women who are breastfeeding or pregnant.
- Any evidence of clinically active interstitial lung disease.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both