Low Dose Daily Erlotinib in Combination With High Dose Twice Weekly Erlotinib in Patients With EGFR-Mutant Lung Cancer
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 Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase 1 Trial of Low Dose Daily Erlotinib in Combination With High Dose Twice Weekly Erlotinib in Patients With EGFR-Mutant Lung Cancer|
- to determine the maximum tolerated dose (MTD) [ Time Frame: 1 year ]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.
- to evaluate the safety profile [ Time Frame: 1 year ]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.
- Progression Free Survival (PFS) [ Time Frame: 1 year ]Progression free survival (PFS) is defined as the duration of time from first treatment to time of progression or death, whichever occurs first.
- Response rate (RR) [ Time Frame: 1 year ]sum of complete responses and partial responses according to RECIST 1.1
- Overall survival (OS) [ Time Frame: 1 year ]Overall survival (OS) is defined as the duration of time from first treatment to time of death.
|Study Start Date:||October 15, 2013|
|Estimated Study Completion Date:||October 2018|
|Estimated Primary Completion Date:||October 2018 (Final data collection date for primary outcome measure)|
This protocol is a phase 1, single arm, open label study of combination daily low dose erlotinib plus twice weekly high dose erlotinib in patients with EGFR-Mutant lung cancer who have not yet received erlotinib or gefitinib. Six dose levels are planned for escalation, with the pulse dose erlotinib increasing.
Expansion cohort A: Treat an additional 19 pts at the MTD with CNS involvement at diagnosis
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01967095
|United States, New Jersey|
|Memoral Sloan Kettering Cancer Center|
|Basking Ridge, New Jersey, United States|
|United States, New York|
|Memorial Sloan Kettering Commack|
|Commack, New York, United States, 11725|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Memorial Sloan Kettering Rockville Centre|
|Rockville Centre, New York, United States, 11570|
|Memoral Sloan Kettering Cancer Center at Phelps|
|Sleepy Hollow, New York, United States, 10591|
|Principal Investigator:||Helena Yu, MD||Memorial Sloan Kettering Cancer Center|