Randomized RT +/- Lapatinib for Advanced Solid Tumor Cancer Patients Receiving Radiation Therapy for Metastatic Disease

Lapatinib is an orally bioavailable small molecule inhibitor of ERBB1 and ERBB2 (HER2). It
is currently indicated for use in patients with HER2 over-expressing metastatic breast
cancer. Serum increases in TGFα can have growth potentiating effects on distant sites of
metastatic disease. Palliative irradiation paradoxically may promote distant tumor growth;
blocking shedding of TGFα from irradiated tumors may prevent this effect and improve the
therapeutic index of radiation therapy.

Inclusion Criteria:

- History of stage IV epithelial-derived cancer requiring palliative radiation.
Patients with sarcoma, lymphoma, myeloma or neuroendocrin cancers are not eligible.

- Evidence of metastatic disease

- Recommendation by patient's radiation oncologist to receive palliative external beam
radiation for metastases -- minimum fraction size of 3 Gy.

- Age 18 years or older

- Patients may be undergoing concurrent therapy with GNRH agonists or combined androgen
blockade or anti-estrogen hormonal therapy for breast cancer, as these are standard
care for advanced prostate and some breast cancers respectively.

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Any contraindication to lapatinib treatment.

- Prior radiation therapy within 30 days of the start of the planned course of
treatment.

- Prior cytotoxic chemotherapy within 4-2 weeks of planned first dose of radiation.
Persistent grade 2 or greater non-hematologic toxicity (other than neuropathy) from
cytotoxic chemotherapy regardless of interval since last dose. Persistent grade 3 or
greater hematologic toxicity (other than lymphopenia) reglardless of interval since
last dose.

- Prior administration of an ERBB1 or ERK1/2 inhibitor within 30 days of the start of
the planned course of treatment.

- Patients with a medical necessity to continue active therapy with CYP3A4 strong
inhibitors or inducers. The concomitant use of strong CYP3A4 inhibitors should be
avoided (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir,
nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole,
aprepitant). Grapefruit may also increase plasma concentrations of lapatinib and
should be avoided. Once the strong inhibitor or inducer is discontinued, a washout
period of approximately 1 week should be allowed before the lapatinib administration.
If a patient is unable to discontinue these medications, they are not eligible for
enrollment.

- Concurrent administration of any other investigational agents.

- Uncontrolled concurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, active hepatic or biliary disease with a Child-Pugh class of B or C, or
psychiatric illness/social situations that would limit compliance with study
requirements or that would interfere with accomplishing the study objectives.

- Pregnant or nursing. Women of childbearing potential must have a negative pregnancy
test performed within 7 days prior to the start of treatment. Women of childbearing
potential and men must agree to use a medically accepted form of birth control for
the duration of study participation. Men must agree to use a medically accepted form
of birth control for 4 months following completion of study treatment.