S0528 Lapatinib and Everolimus in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma
S0528 Lapatinib and Everolimus in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma
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.
OBJECTIVES:

 -  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.
DISEASE CHARACTERISTICS:

 -  Histologically or cytologically confirmed advanced solid tumor or non-Hodgkin's
 lymphoma for which no curative options exist

 -  Measurable or nonmeasurable disease

 -  Patients with brain metastases who require corticosteroids or anticonvulsants must be
 on a stable or decreasing dose of corticosteroids and seizure free for 30 days prior
 to study entry

 -  Patients with known brain metastases must have had brain irradiation (whole brain
 or gamma knife)

 -  No untreated (non-irradiated) brain metastases

 PATIENT CHARACTERISTICS:

 -  Zubrod performance status 0-2

 -  Absolute neutrophil count ≥ 1,500/mm³

 -  Platelet count ≥ 100,000/mm³

 -  SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases
 are present)

 -  Bilirubin normal

 -  Creatinine normal OR creatinine clearance > 60 mL/min

 -  Cardiac ejection fraction normal by echocardiogram or MUGA

 -  Able to swallow enteral medications

 -  No feeding tubes

 -  No intractable nausea or vomiting

 -  No gastrointestinal (GI) tract disease resulting in an inability to take oral
 medication

 -  No current active hepatic or biliary disease with the exception of Gilbert's syndrome
 or asymptomatic gallstones

 -  No malabsorption syndrome

 -  No requirement for IV alimentation

 -  No uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis)

 -  No history of allergic reactions attributed to compounds of similar chemical or
 biologic composition to lapatinib or everolimus, including other quinazoline
 compounds, such as gefitinib and erlotinib, or other rapamycins, such as sirolimus and
 temsirolimus

 -  No known HIV positivity

 -  No concurrent uncontrolled illness, including, but not limited to, any of the
 following:

 -  Ongoing or active infection

 -  Symptomatic congestive heart failure

 -  Unstable angina pectoris

 -  Cardiac arrhythmia

 -  Myocardial infarction or cerebrovascular accident within the past 3 months

 -  Uncontrolled diarrhea

 -  Psychiatric illness or social situation that would preclude compliance with study
 requirements

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  Fertile patients must use effective contraception

 -  Willing to undergo pharmacokinetic (PK) sampling and blood collection for PK and
 correlative studies (for patients enrolled in part II)

 PRIOR CONCURRENT THERAPY:

 -  See Disease Characteristics

 -  Recovered from prior therapy

 -  No prior lapatinib or everolimus

 -  No prior surgical procedures affecting absorption

 -  More than 14 days since prior major surgery, chemotherapy (42 days for nitrosoureas or
 mitomycin C), or radiotherapy

 -  More than 28 days since prior investigational agents

 -  At least 7 days since prior and no concurrent CYP3A4 inhibitors

 -  At least 14 days since prior and no concurrent CYP3A4 inducers

 -  At least 14 days since prior and no concurrent herbal or dietary supplements

 -  No concurrent chemotherapy, hormone therapy, radiotherapy, immunotherapy, live
 vaccines or any other anticancer therapy

 -  Concurrent luteinizing hormone-releasing hormone agonists allowed

 -  Concurrent bisphosphonates or epoetin alfa or its analogue allowed

 -  No concurrent gastric H2 blockers (e.g., cimetidine, ranitidine, nizatidine,
 famotidine) or proton pump inhibitors (e.g., omeprazole, esomeprazole, rabeprazole,
 pantoprazole, or lansoprazole)

 -  Antacids allowed provided they are not administered within 1 hour before and
 after lapatinib

 -  No concurrent glucocorticoids or immunosuppressants