Phase I Study of Two Different Schedules of Lapatinib (GW572016) in Combination With Vinorelbine in Advanced Solid Tumors

Inclusion Criteria:

- Cytologically or histologically proven advanced solid tumors for which there is no
known standard therapy available or are not eligible for standard therapy because of
their performance status, or have progressed after no more than 2 prior chemotherapy
regimens for metastatic disease.

- Measurable or evaluable disease. Disease in previously irradiated sites is
considered measurable if there is clear disease progression following radiation
therapy.

- 18 years of age or older.

- Zubrod performance status of 0-2.

- Estimated survival of at least 3 months.

- Any prior chemotherapy must have been completed at least 4 weeks prior to start of
this protocol and all side effects (except alopecia) resolved to grade 1 or less.
Any prior radiation must have been completed at least 2 weeks prior to start of
therapy. For prior mitomycin chemotherapy a 6-week interval is required. Patients
must have completed prior trastuzumab at least 4 weeks prior to start of protocol
therapy.

- Adequate renal function

- Adequate liver function

- Pretreatment granulocyte count of >1500/mm3 and platelet count of >100 000/mm3.

- Cardiac ejection fraction within the institutional range of normal as measured by 2-D
echocardiogram or MUGA scan.

- Asymptomatic treated brain metastasis may be included if they are neurologically
stable and have been off steroids and anticonvulsants for at least 4 weeks.

- All patients must give informed consent.

- Able to take and retain oral medication.

- Patients of reproductive potential must agree to use an effective contraceptive
method

Exclusion Criteria:

- Patients may not have previously received lapatinib, vinorelbine or any other EGFR-1
targeted agent. Prior trastuzumab is allowed.

- Females cannot be pregnant or breastfeeding

- Symptomatic brain metastasis or still requiring steroids and anticonvulsants may not
participate.

- Pre-existing neuropathy > grade 2 may not participate.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements, will be excluded.

- History of other diseases, metabolic dysfunction, physical examination finding or
clinical laboratory finding giving reasonable suspicion of a disease or condition
that contraindicates the use of an investigational drug or that might affect the
interpretation of the results of the study or render the patient at high risk from
treatment complications.

- Gastrointestinal tract disease resulting in an inability to take oral medication or a
requirement for IV alimentation, or prior surgical procedures affecting absorption.

- HIV-positive patients receiving combination anti-retroviral therapy are excluded from
the study because of possible pharmacokinetic interactions with lapatinib.

- Patients requiring oral anticoagulants are eligible provided there is appropriate
close INR monitoring is in place. If medically appropriate and treatment available,
the investigator may also consider switching these patients to LMW heparin, where an
interaction with lapatinib is not expected.

- Adherence to the requirements for concomitant medications classified as CYP3A4
inducers or inhibitors, or gastric pH modifiers