A Study In Patients Who Will Undergo Surgical Removal Of Non-Small Cell Lung Cancer To Evaluate Molecular Changes That Occur In Tumor Tissue After Short Term Exposure To PF-00299804

Study Overview
=================
Brief Summary
-----------------
This study will enroll patients who are planned to undergo surgical removal of their tumor. The goal of the study is to evaluate the changes that occur in the tumor after brief (about 8 days) exposure to the study drug.

Detailed Description
-----------------
The A7471031 study was terminated on May 2, 2012. The decision for unplanned study termination was triggered by feasibility of further conduct of this trial as only 22 of the protocol-specified 75 patients were enrolled since the study initiated in February 2010. Based on this low accrual rate it was determined that the study was highly unlikely to complete accrual and provide meaningful data. The discontinuation of the study is not due to any safety issue.

Official Title
-----------------
A Presurgical Study To Evaluate Molecular Changes That Occur In Human Non-Small Cell Lung Cancer Tissue After Short Term Exposure To PF-00299804

Conditions
-----------------
Non-Small Cell Lung Cancer (NSCLC)

Intervention / Treatment
-----------------
* Drug: PF-00299804


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Radiographs consistent with lung cancer for which resection is indicated upon histologic confirmation of non-small cell lung cancer. Patient willing to take PF-00299804 for 5 to 11 days and provide blood and tissue specimens as required in the study. Exclusion Criteria: Prior or concurrent systemic anticancer therapy for cancer (immunotherapy, hormonotherapy, biological therapy, or chemotherapy) less than one year from time of consent. Prior or concurrent radiation therapy to tumor at site of planned resection. Congestive heart failure (LVEF < 50%), uncontrolled hypertension, significant ventricular arrythmia. Drugs that are highly dependent on CYP2D6 for metabolism, or are generally accepted to have a risk of causing Torsades de Pointes. Prior or concurrent radiation therapy to tumor at site of planned resection.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment<br>Patients treated with brief exposure to PF-00299804 prior to surgical resection | Drug: PF-00299804<br>* Brief exposure (5- 11 days) to study drug prior to surgical resection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To identify the molecular changes which occur in human non-small cell lung cancer tissue after short-term exposure to PF-00299804 administered at 45 mg daily after a loading dose |  | 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To correlate molecular changes with specific gene and protein changes (eg, mutations, amplifications, over expression) in members of the EGFR and HER2 signal transduction pathways (eg, KRAS, EGFR, HER2) |  | 30 months | 
| To assess the effect of short term treatment of PF-00299804 on serum levels of the extracellular domain of EGFR and other serum markers of HER signaling (eg, serum HER2/neu and serum E-cadherin) |  | 30 months | 
| To assess the relationship between the pharmacokinetic parameters with molecular changes detected in non-small cell lung cancer |  | 30 months | 
| To assess the safety and tolerability of PF-00299804 in this setting |  | 30 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Stage I - III surgical resection molecular change brief pre-operative exposure