S0528 Lapatinib and Everolimus in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma
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|ClinicalTrials.gov Identifier: NCT00352443|
Recruitment Status : Completed
First Posted : July 14, 2006
Last Update Posted : March 6, 2015
RATIONALE: Lapatinib and everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Everolimus may also stop the growth of cancer cells by blocking blood flow to the cancer. Giving lapatinib together with everolimus may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of lapatinib and everolimus in treating patients with advanced solid tumors or non-Hodgkin's lymphoma.
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma Unspecified Adult Solid Tumor, Protocol Specific||Drug: everolimus Drug: lapatinib ditosylate||Phase 1|
- 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 toxicity.
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 pharmacokinetic studies.
After finishing treatment, patients are followed periodically for 28 days.
PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||66 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study Evaluating the Combination of Lapatinib (GW572016; NSC-727989) and Everolimus (RAD001) in Patients With Advanced Solid Tumors|
|Study Start Date :||September 2006|
|Primary Completion Date :||August 2007|
|Study Completion Date :||September 2013|
Part 1, dose finding: everolimus and lapatinib at assigned dose daily Part 2, cohort A: Everolimus MTD from Part I: 5 mg PO 1-28 Daily Lapatinib MTD from Part I: 1,250 mg PO Cycle 1, Daily Days 8-28** Subsequent Cycles, Days 1-28 Part 2, cohort B: Lapatinib MTD from Part I: 1,250 mg PO 1-28 Daily Everolimus MTD from Part I: 5 mg PO Cycle 1, Daily Days 8-28** Subsequent Cycles, Days 1-28
part 1: dose assigned by ETx online system PO days 1-28 daily part 2: cohort a: 5 mg PO days 1-28 part 2: cohort a: 1250 mg PO days 8-28 (cycle 1) days 1-28 (subsequent cycles)Drug: lapatinib ditosylate
dose assigned by ETx online system PO days 1-28 daily part 2 cohort a: 1250 mg PO d 8-28 (cycle 1) days 1-28 (subsequent cycles) part 2 cohort b: 120 mg PO days 1-28 daily
- Maximum tolerated dose of lapatinib and everolimus (Part I) [ Time Frame: 1 month ]
- Pharmacokinetics (Part II) [ Time Frame: 1 month ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00352443
|United States, California|
|USC/Norris Comprehensive Cancer Center and Hospital|
|Los Angeles, California, United States, 90089-9181|
|University of California Davis Cancer Center|
|Sacramento, California, United States, 95817|
|United States, Colorado|
|University of Colorado Cancer Center at UC Health Sciences Center|
|Aurora, Colorado, United States, 80045|
|United States, Kentucky|
|Lucille P. Markey Cancer Center at University of Kentucky|
|Lexington, Kentucky, United States, 40536-0093|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center|
|Ann Arbor, Michigan, United States, 48109-0942|
|United States, Washington|
|University Cancer Center at University of Washington Medical Center|
|Seattle, Washington, United States, 98195-6043|
|Study Chair:||Shirish M. Gadgeel, MD||Barbara Ann Karmanos Cancer Institute|
|Principal Investigator:||Patricia M. LoRusso, DO||Barbara Ann Karmanos Cancer Institute|