Phase I Study Evaluating the Combination of Lapatinib (GW572016; NSC-727989) and Everolimus (RAD001) in Patients With Advanced Solid Tumors
- Estimate the maximum tolerated dose (MTD) of lapatinib and everolimus in patients with
advanced solid tumors or non-Hodgkin's lymphoma. (Part I)
- Investigate the pharmacokinetics of everolimus and lapatinib (when given alone and in
combination) at the MTD determined in Part I. (Part II)
- Investigate the effects of everolimus and lapatinib (when given alone and in
combination) on serum levels of vascular endothelial growth factor (VEGF), basic
fibroblast growth factor (bFGF), matrix metalloproteinase (MMP)-2 and MMP-9,
interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). (Part II)
OUTLINE: This is a multicenter, dose-escalation study followed by a randomized study.
Initial patients enrolled on the study are treated in part I. After the maximum tolerated
dose (MTD) is determined in part I, subsequent patients are enrolled and treated in part II.
- Part I: Patients receive oral everolimus and oral lapatinib once daily on days 1-28.
Courses repeat every 28 days in the absence of disease progression or unacceptable
Cohorts of 3-6 patients receive escalating doses of everolimus and lapatinib until the MTD
is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients
experience dose-limiting toxicity.
- Part II: Patients are randomized to 1 of 2 treatment arms. Everolimus and lapatinib are
administered at the MTD determined in part I.
- Arm I: Patients receive oral everolimus once daily on days 1-28. Patients also
receive oral lapatinib once daily on days 8-28 during the first course and on days
1-28 during all subsequent courses. Courses repeat every 28 days in the absence of
disease progression or unacceptable toxicity.
- Arm II: Patients receive oral lapatinib once daily on days 1-28. Patients also
receive oral everolimus once daily on days 8-28 during the first course and on
days 1-28 during all subsequent courses. Courses repeat every 28 days in the
absence of disease progression or unacceptable toxicity.
Patients in part II undergo blood collection periodically for correlative biomarker and
After finishing treatment, patients are followed periodically for 28 days.
PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of lapatinib and everolimus (Part I)
Shirish M. Gadgeel, MD
Barbara Ann Karmanos Cancer Institute
United States: Federal Government
|University of Michigan Comprehensive Cancer Center||Ann Arbor, Michigan 48109-0752|
|USC/Norris Comprehensive Cancer Center and Hospital||Los Angeles, California 90033-0804|
|University of California Davis Cancer Center||Sacramento, California 95817|
|University Cancer Center at University of Washington Medical Center||Seattle, Washington 98195|
|Lucille P. Markey Cancer Center at University of Kentucky||Lexington, Kentucky 40536-0093|
|University of Colorado Cancer Center at UC Health Sciences Center||Aurora, Colorado 80045|