Phase I Trial of the Combination of Dasatinib and Lapatinib

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed advanced solid tumor

- Unresectable disease

- Must be refractory to or have refused all standard treatment for the disease

- Willing to provide the biologic specimens (cohort II only)

- No known standard therapy for disease that is not refractory to treatment that is
potentially curative or definitely capable of extending life expectancy

- No CNS metastases that are not stable for at least 4 weeks prior to registration
based on imaging, clinical assessment, and use of steroids

- No uncontrolled pleural or pericardial effusion of any grade

PATIENT CHARACTERISTICS:

Inclusion criteria:

- ECOG performance status 0-2

- Life expectancy ≥ 12 weeks.

- Absolute neutrophil count ≥ 1,500/μL

- Platelet count ≥ 100,000/μL

- Total bilirubin ≤ upper limit of normal (ULN)

- AST ≤ 3 times ULN (5 times ULN if liver involvement)

- Creatinine ≤ 1.5 times ULN

- Hemoglobin ≥ 9.0 g/dL

- Potassium and magnesium must be within normal limits

- LVEF > 50% by ECHO

- Able to swallow pills

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for at least 4 weeks
after completion of study therapy

Exclusion criteria:

- Uncontrolled infection

- New York Heart Association classification III or IV

- Seizure disorder

- Uncontrolled angina, congestive heart failure, or myocardial infarction within the
past 6 months

- Diagnosed congenital long-QT syndrome

- History of clinically significant ventricular arrhythmias (such as ventricular
tachycardia, ventricular fibrillation, or torsades de pointes)

- Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec)

- Hypokalemia or hypomagnesemia that cannot be corrected

- Diagnosed congenital bleeding disorders (e.g., von Willebrand disease)

- Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII
antibodies)

- Ongoing or recent (≤ 3 months prior to registration) significant gastrointestinal
bleeding

- Gastrointestinal conditions that may interfere with drug absorption such as
ulcerative colitis, Crohn disease, and short bowel syndrome

PRIOR CONCURRENT THERAPY:

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin C)
and recovered

- More than 4 weeks since prior immunotherapy, or biologic therapy (i.e., bevacizumab,
trastuzumab [Herceptin®], or cetuximab)

- More than 4 weeks since prior molecular target agents (i.e., erlotinib hydrochloride,
sunitinib malate, sorafenib tosylate, gefitinib, imatinib mesylate)

- More than 4 weeks since prior radiotherapy

- No prior radiotherapy to > 25% of bone marrow

- No other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary
therapy considered investigational

- No concurrent therapy with a CYP3A4 inhibitor or inducer

- No concurrent prophylactic colony-stimulating factors