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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
53
Cycle 1, week 1 (D1-D7) will consist of pulse dose erlotinib on D1 \& D2 without daily low dose erlotinib on D3-7. For all subsequent weeks, patients will take high dose erlotinib on D1 \& D2, \& will receive erlotinib 50 mg oral daily x 5 days on days 3-7. On days 1 \& 2, patients will take one of the following doses of erlotinib, depending on the dose cohort they are enrolled in: Dose level 1 600 mg oral daily on D1, D2 Dose level 2 750 mg oral daily on D1, D2 Dose level 3 900 mg oral daily on D1, D2 Dose level 4 1050 mg oral daily on D1, D2. An additional Dose -1 (pulse dose erlotinib on D1, D2 with 25 mg oral daily x 5 days in D3-D7) will be reserved, in the unlikely situation that Dose 1 is proved too toxic. If Dose -1 is tolerated well (600mg oral daily D1, D2 \& 25mg oral daily D3-D7), pulse dose escalation can continue as described above, with erlotinib at the daily low dose of 25 mg oral on D3-D7.
Memoral Sloan Kettering Cancer Center
Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Commack
Commack, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Memorial Sloan Kettering Rockville Centre
Rockville Centre, New York, United States
Memoral Sloan Kettering Cancer Center at Phelps
Sleepy Hollow, New York, United States
to determine the maximum tolerated dose (MTD)
The study will use a standard 3+3 dose escalation design. Three to six patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (28 days for cycle 1) before dose escalation decision is made.
Time frame: 1 year
to evaluate the safety profile
Toxicity will be graded according to NCI CTCAE, version 4.0. The analysis of safety/tolerability data will be descriptive; toxicity events will be individually tabulated.
Time frame: 1 year
Progression Free Survival (PFS)
Progression free survival (PFS) is defined as the duration of time from first treatment to time of progression or death, whichever occurs first.
Time frame: 1 year
Response rate (RR)
sum of complete responses and partial responses according to RECIST 1.1
Time frame: 1 year
Overall survival (OS)
Overall survival (OS) is defined as the duration of time from first treatment to time of death.
Time frame: 1 year
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