A Window of Opportunity Trial of Afatinib In Early Stage Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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This study is for patients that have Non-Small Cell Lung Cancer (NSCLC) and he or she will have surgery to remove the tumor. The main purpose of this study is to study how safe and suitable treatment with Afatinib is in participants before surgery to remove the tumor. Another goal of the study is to see if treatment with Afatinib affects the growth and activity of the tumor. Afatinib has not been approved for use by the FDA (Food and Drug Administration) and is experimental. In some persons, the growth of cancer cells is thought to be stimulated by Epidermal Growth Factor (EGF). This is a protein found in the body which binds to the cell wall to sites called receptors and stimulates cell growth. Some cells have too many receptors and uncontrolled growth and because of this, develop into a cancer tumor. There are several other cancer drugs that bind to these receptors to slow or stop cancer growth such as Gefitinib and erlotinib which are FDA approved and used for the treatment of NSCLC. The drug Afatinib has been shown to inhibit mutated EGF receptors in clinical trials and may be a candidate for the treatment of NSCLC and a variety of early stage cancers. Participants in this study will take Afatinib by mouth, in pill form, for at least 14 days before having their scheduled surgery to remove their cancer tumor. Participants will be observed for side effects and followed for 30 days after surgery to assess the results after surgery.

Official Title
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A Therapeutic Trial of Afatinib in the Neoadjuvant Setting. Molecular Effects of Afatinib: A Window of Opportunity Trial In Early Stage NSCLC

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: BIBW 2992 (Afatinib)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed NSCLC, who are deemed to be surgical candidates by standard criteria. Patients with all histologies will be allowed to enroll. Patients with Stage IA to IIIA disease ECOG Performance Status 0-1 Measurable disease by RECIST 1.1 criteria Mediastinoscopy and/or Endoscopic Bronchial Ultrasound (EBUS) and/or Endoscopic Ultrasound (EUS) for complete surgical staging when clinically indicated Total bilirubin ≤1.5 mg/dl, SGOT (AST) and SGPT (ALT)≥ 3 x ULN Serum creatinine ≤ 1.5 mg/dl Serious, active infections must be controlled. Patients may be enrolled while still on antibiotics as long as clinical signs of active infection have resolved. A signed informed consent document (ICD) Patients 18 years or older Able and willing to take oral medications Exclusion Criteria: Known preexisting lung disease. History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to randomization. Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g. Crohn's disease, malabsorption or CTC grade ≥2 diarrhea of any etiology. Baseline (<1 month before treatment) cardiac left ventricular function with resting ejection fraction of less than 50% measured by multigated blood pool imaging of the heart (MUGA scan) or echocardiogram Patients may not be receiving any other investigational agents. History of allergic reactions to anilinoquinazolins like gefitinib, erlotinib or BIBW 2992 Uncontrolled intercurrent illness that would preclude a patient from undergoing surgery Psychiatric illness/social situations that would limit compliance with study requirements. Pregnant (positive pregnancy test) or lactating Inability to comply with study and/or follow-up procedures Patients who are not surgical candidates or refuse surgery

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm Study<br>Single arm trial where all patients will be treated with afatinib until the day of surgery and for a minimum of two weeks. Patients will receive treatment with afatinib 40mg orally daily. | Drug: BIBW 2992 (Afatinib)<br>* Patients will receive treatment with afatinib 40mg orally daily for a minimum of 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility | The primary endpoint will demonstrate feasibility of neoadjuvant treatment of BIBW 2992 in patients with early stage (IA to IIIA) NSCLC awaiting surgical resection. Feasibility will be assessed based on the ability to complete the treatment for each patient. For our feasibility endpoint we will declare the treatment completed if a patient completes at least 14 days of treatment, had a thoracotomy for the planned surgical resection, and 30 days of post operative care. | 30 days post operative care | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Efficacy | The secondary objective is to determine whether pre-operative BIBW 2992 treatment affects metabolic tumor labeling, as measured by PET-CT scanning. We will measure the absolute and the percentage change in SUV from baseline to follow-up. | 30 post operative care |