Afatinib sequenced with concurrent chemotherapy and radiation in EGFR-Mutant non-small cell lung tumors: The ASCENT trial

This research study is a Phase II clinical trial. Phase II clinical trials test the
effectiveness of an investigational drug to learn whether the drug works in treating a
specific cancer. "Investigational" means that the drug is still being studied and that study
doctors are trying to find out more about it-such as the safest dose to use, the side effects
it may cause, and if the drug is effective for treating different types of cancer. It also
means that the FDA has not yet approved the drug for the patients type of cancer or for any
use outside of research studies.

Chemotherapy and radiation is the standard treatment for the patients with stage III
non-small cell lung cancer (NSCLC). For people with epidermal growth factor receptor (EGFR)
mutations, adding a type of drug called a tyrosine kinase inhibitor (TKI) can help increase
the response to treatment.

Afatinib is a tyrosine kinase inhibitor. It has been studied in a previous research study in
participants with more advanced NSCLC. Results from that study indicate it may be helpful in
treating NSCLC with EGFR mutations.

In this study, patients with stage III NSCLC and EGFR mutations will receive the standard
treatment of radiation and chemotherapy. If possible, the patients tumor will be removed by
surgery. Afatinib will be given before radiation and chemotherapy and after surgery. The aim
of giving afatinib before radiation therapy is to try to shrink the tumor. This may make the
radiation therapy more effective since radiation therapy tends to work better on smaller
tumors.

The goal of this study is to see if adding afatinib to standard treatment helps to improve
the response to treatment.

Inclusion Criteria:

- Histologically confirmed stage IIIA NSCLC

- Measurable disease

- Have lung cancer harboring an EGFR mutation

- Must be evaluated by a medical oncologist, radiation oncologist and thoracic surgeon
within 4 weeks of enrollment into study to document that they are a candidate for
chemoradiation and for consideration of surgical resection (not required to be a
surgical candidate)

Exclusion Criteria:

- Pregnant or breastfeeding

- Prior EGFR TKI therapy

- Prior treatment with radiation to the thoracic region (including breast irradiation)

- Known pre-existing interstitial lung disease

- Significant or recent gastrointestinal disorders with diarrhea as a major symptom

- History or presence of relevant cardiovascular abnormalities

- Any other concomitant serious illness or organ system dysfunction

- Active hepatitis B, C or known HIV carrier

- Known or suspected active drug or alcohol use

- Known hypersensitivity to afatinib, cisplatin, or pemetrexed

- Concomitant treatment with strong inhibitor of P-gp

- History of an active malignancy within the last 3 years