A Phase I/II Study of Foretinib in Patients With Previously Treated Non-Small Cell Lung Cancer Receiving Standard Erlotinib Therapy
- To determine the recommended phase II dose of MET/VEGFR2 inhibitor Foretinibin
combination with standard erlotinib hydrochloride therapy in patients with locally
advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one
prior chemotherapy regimen, and whose EGFR-expression status is positive or unknown.
- To determine the safety, tolerability, toxicity profile, dose-limiting toxicities, and
pharmacokinetic profile of MET/VEGFR2 inhibitor Foretinib and erlotinib hydrochloride
in this schedule.
- To determine the correlation, if any, between the toxicity profile and
- To assess the anti-tumor activity of MET/VEGFR2 inhibitor Foretinib in combination with
erlotinib hydrochloride as evidenced by response rates, clinical benefit (complete or
partial response or stable disease ≥ 8 weeks duration), and an exploratory endpoint of
early assessment of tumor size as a continuous variable (when compared to erlotinib
- To assess one-year survival rate in these patients.
- To investigate the correlation, if any, between response and biomarkers, including EGFR
gene mutation, EGFR gene amplification, EGFR gene polymorphisms, c-Met gene mutation,
amplification and expression, phospho-c-Met expression, K-Ras gene mutation, and
baseline serum HGF levels.
OUTLINE: This is a multicenter, dose-escalation phase I study of MET/VEGFR2 inhibitor
Foretinib followed by a randomized, open-label phase II study.
- Phase I (dose-escalation) : Patients receive oral erlotinib hydrochloride once daily on
days 1-28. Patients receive oral MET/VEGFR2 inhibitor GSK1363089 once daily on days
15-28 during course 1 and on days 1-28 during all other courses. Courses repeat every
28 days until the maximum-tolerated dose of MET/VEGFR2 inhibitor Foretinib is
Blood samples are collected on days 14 and 28 of course 1 for pharmacokinetics and day 1 of
courses 1 and 2 and post treatment for pharmacodynamic studies.
- Phase II: Patients are randomized to 1 of 2 treatment arms:
- Arm I (MET/VEGFR2 inhibitor Foretinib and erlotinib hydrochloride): Patients
receive oral MET/VEGFR2 inhibitor Foretinib (at the recommended phase II dose
determined in phase I) once daily and oral erlotinib hydrochloride once daily on
days 1-28. Courses repeat very 28 days in the absence of disease progression or
- Arm II (erlotinib hydrochloride only): Patients receive oral erlotinib
hydrochloride once daily on days 1-28. Courses repeat every 28 days in the absence
of disease progression or unacceptable toxicity.
In both arms, samples are collected for pharmacodynamic studies as in phase I.
After completion of study treatment, patients are followed at week 4 and then every 3 months
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The recommended phase II dose of daily oral MET/VEGFR2 inhibitor Foretinib when given in combination with standard erlotinib hydrochloride therapy (phase I)
After completion of Phase I portion of the study
Natasha Leighl, MD, FRCPC
Princess Margaret Hospital, Canada
Canada: Health Canada