This trial is for patients with colon cancer, head and neck cancer and lung cancer that has not responded to standard therapy.

Cetuximab targets a receptor on cancer cells called the Epidermal Growth Factor Receptor or EGFR. It is thought that this receptor is turned "on" in some cancers, enabling cancer cells to divide and grow. Blocking this receptor can turn this signal off. Cetuximab blocks this receptor from the outside of cancer cells. It is thought that cancer cells can turn this signal back on by the EGFR joining with a related receptor called ErbB2. Lapatinib blocks both EGFR and ErbB2 from the inside of cancer cells. In laboratory experiments it has been found that combining drugs that target both EGFR and ErbB2 might work better in turning this signal back off. The purpose of this study is to determine the maximum dosages that patients can tolerate when these two medicines are given at the same time.

In addition, in order to be on this trial, patients must agree to have a tumor biopsy before starting treatment on this study and 21 days after starting treatment. These biopsies are a required part of the study. Patients must also agree to have blood drawn for research testing to see whether genetic differences between patients explain different reactions to and side effects from, these medicines.

Inclusion Criteria:

• At least one measurable lesion by RECIST criteria
• A tumor lesion that can be readily biopsied using a core needle via clinical exam, ultrasound, CT, or fluoroscopic-guidance
• Over the age of 18 years and able to provide informed consent
• Patients must have progressed after standard therapy for metastatic/ recurrent disease including 5-FU containing regimens for patients with colorectal cancer, and platinum-containing regimens for patients with head and neck cancer and non-small cell lung cancer.
• Patients may have received cetuximab, panitumumab or erlotinib previously
• Adequate kidney, liver, and bone marrow function
• Life expectancy greater than 3 months
• ECOG performance status </= 2
• Normal left ventricular ejection fractions

Exclusion Criteria:

• Chemotherapy or surgery within 4 weeks prior to treatment start
• Radiation treatment within 3 weeks prior to treatment start
• Prior therapy with lapatinib
• Untreated brain metastasis or neurologically unstable CNS metastases
• Any severe or uncontrolled medical condition or other condition that could affect participation in this study including unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction </= 6 months prior to study entry
• Diarrhea > grade 1 at baseline
• Patients on a medication or herbal therapy known to inhibit CYP3A4
• Gastrointestinal tract disease resulting in the inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption or active peptic ulcer disease
• Ongoing ventricular cardiac dysrhythmias of grade >/= 2
• Subjects with a history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation >= 3 beats in a row)
• Serious cardiac arrhythmia requiring medication
• QTc interval > 500 msec
• Female patients who are pregnant or breast feeding, or adults who are of reproductive potential and are unwilling to refrain from conceiving a child during study treatment
• Patients unwilling or unable to comply with the protocol or provide informed consent