Afatinib With CT and RT for EGFR-Mutant NSCLC

Conditions:Lung Cancer, Cancer
Therapuetic Areas:Oncology
Age Range:18 - Any
Start Date:April 2012
End Date:December 2020
Contact:Lecia V Sequist, MD MPH

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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

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

Study treatment will be divided into 5 stages:

Stage 1-induction, consisting of afatinib for two 4-week cycles. Afatinib is a pill that the
patient takes by mouth once per day. The patient will receive a study drug diary in which to
record the doses of afatinib.

Stage 2-concurrent radiation and chemotherapy with cisplatin/pemetrexed for two 3-week

Stage 3-Surgery to remove tumor for participants whose tumor can be removed by surgery. This
will be done about 4-6 weeks after finishing radiation and chemotherapy. The exact timing
will depend upon how quickly the patient recovers from side effects of the radiation and
chemotherapy. The investigators will use a piece of the patients tumor removed by surgery for
research tests to look for biomarkers such as genes and proteins that may be associated with
response to afatinib, chemotherapy or radiation.

Stage 4-Chemotherapy after surgery (adjuvant chemotherapy). The patients doctor will decide
if the patient will receive chemotherapy after the patients surgery but before receiving
consolidation with afatinib. If the patient does receive this, it will start 6-12 weeks after
surgery or finishing radiation if the patient does not have surgery. The chemotherapy will be
the same as that received along with the radiation therapy.

Stage 5-Consolidation with afatinib for twenty-six 4-week cycles (2 years) for participants
who responded to the 2 cycles of induction afatinib.

The investigators would like to keep track of the patients medical condition and status of
the patients disease for up to 5 years after the patient stops study treatment. Keeping in
touch with the patients and checking on the patients condition every year helps the
investigators look at the long-term effects of the research study. The patients will be asked
to have CT scans as follows:

- Every 3 months for the first year after stopping study treatment

- Every 6 months for years 2-4 after stopping study treatment

- Once per year in year 5 after stopping study 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
We found this trial at
185 Cambridge Street
Boston, Massachusetts 02114
Principal Investigator: Lecia V Sequist, MD MPH
Phone: 617-724-4000
Boston, MA
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450 Brookline Ave
Boston, Massachusetts 2215
Principal Investigator: Geoffrey Oxnard, MD
Phone: 617-632-6049
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
Boston, MA
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