Phase I Study Evaluating the Combination of Lapatinib (GW572016; NSC-727989) and Everolimus (RAD001) in Patients With Advanced Solid Tumors

Inclusion Criteria

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