Understanding Mechanisms of Acquired Resistance to BIBW2992

• To estimate the response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• To estimate the progression-free and overall survival. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• To describe the safety of obtaining repeat tumor biopsies for genotype analysis. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

In this research study we are looking to see how effective BIBW 2992 is at suppressing the development of the T790M mutation in non-small cell lung cancer (NSCLC) patients. Epidermal growth factor receptors (EGFR) are proteins found on the surface of some cancer cells that promote a growth signal. Some cancer drugs for NSCLC work to block this signal from reaching its target on the cancer cells which in turn may slow or stop the cancer from growing. However, many times patients with EGFR mutations will stop responding to these cancer drugs and develop drug-resistance because they have developed a specific EGFR mutation called T790M. BIBW 2992 my prevent the T790M mutation from becoming active and therefore slow disease progression.

• Participants will take tables of BIBW 2992 once a day during each cycle. Each cycle is 28 days (4 weeks).
• Participants will come to the clinic on Day 1, 8 and 15 of Cycle 1. For Cycle 2 through 8, they woll need to come to the clinic on Day 1. After Cycle 8, they will have study visits every 2 months.
• The following tests and procedures will be performed at these clinic visits: physical examination, routine blood tests, research blood samples, EKG (every fourth cycle starting cycle 5), ECHO or MUGA (every fourth cycle starting cycle 5), an assessment fo the tumor by CT or MRI scan (every 8 weeks).
• Participants may continue to participate in this research study as long as their tumor does not grow and their disease does not worsen and they do not have any severe side effects.
• Participants will have a tumor biopsy performed at the end of their participation in this study if their tumor is growing or if they have a new tumor. The purpose of this biopsy is to assess for the presence or the absence of the mutation T790M.

• Non-small Cell Lung Cancer
• EGFR Mutations

Inclusion Criteria:

• Participants must have histologically or cytologically confirmed stage IIIB, IV or recurrent non-small cell lung cancer
• A somatic mutation in epidermal growth factor receptor (EGFR) must be present as documented by a CLIA-certified laboratory
• There must be radiographic measurable or evaluable disease
• Participants must be willing, at the time of signing consent, to agree to a future biopsy of their tumor tissue at the time of disease progression, provided such a biopsy is safe and feasible at that time.
• Performance status must be 0, 1 or 2 on the Eastern Cooperative Oncology Group scale
• 18 years of age or older
• Normal organ and marrow function as outlined in the protocol
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation

Exclusion Criteria:

• Prior EGFR tyrosine kinase inhibitor therapy (including gefitinib, erlotinib, or any experimental EGFR TKI agents)
• Known brain metastases, unless they have undergone definitive therapy and are neurologically stable at the time of study entry
• Standard chemotherapy or radiation less than 2 weeks of starting BIBW 2992, or experimental systemic cancer therapy less then 4 weeks of starting BIBW 2992. Note that prior palliative radiation to bony disease, CNS disease, or a limited thoracic area is allowed if there is measurable or progressive disease outside the field of radiation.
• Another malignancy within the last 3 years (except for non-melanoma skin cancer or a non-invasive/in situ cancer)
• Known pre-existing and clinically active interstitial lung disease
• Significant gastrointestinal disorders with diarrhea as a major symptom
• History of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia, or myocardial infarction within 6 months
• Cardiac left ventricular function with resting ejection fraction <50%
• Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the study drug
• Pregnancy or breast feeding
• History of allergic reactions attributed to compounds of similar chemical or biologic composition of BIBW 2992
• Life expectancy of < 12 weeks

• University of Texas
• Boehringer Ingelheim Pharmaceuticals