Study of Blood and Tissue Samples in Predicting Response to Second-Line Therapy Using Erlotinib Hydrochloride or Chemotherapy in Patients With Advanced Non-Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Studying the proteins expressed in samples of blood and tissue from patients with cancer may help doctors identify biomarkers related to cancer. It may also help doctors predict how patients will respond to treatment. PURPOSE: This randomized phase III trial is studying blood and tissue samples in predicting response to second-line therapy using erlotinib hydrochloride or chemotherapy in patients with advanced non-small cell lung cancer.

Detailed Description
-----------------
OBJECTIVES: To evaluate the predictive value of proteomic profiling on the effect of second-line therapy with erlotinib hydrochloride vs standard chemotherapy (pemetrexed disodium or docetaxel) in patients with advanced non-small cell lung cancer. To assess the role of other known tissue-based predictive markers (e.g., EGFR-gene copy number, EGFR-protein expression, pAkt, pMAPK, EGFR mutations, EMT markers, and k-Ras mutation). OUTLINE: This is a multicenter study. Patients are stratified according to smoking status, performance status, proteomic profile, and participating center. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive standard chemotherapy with pemetrexed disodium, docetaxel, or another standard drug. Arm II: Patients receive standard non-chemotherapy treatment with erlotinib hydrochloride. Serum is collected after failure of first-line therapy for proteomic analysis by matrix-associated laser desorption/ionization-time of flight. Tissue and blood samples are collected periodically for analysis including EGFR based on IHC and FISH, EGFR and k-Ras mutations, pAkt, pMAPK by IHC, and EMT markers based on IHC and breath condensate protein profile. After completion of study treatment, patients are followed every 2 months.

Official Title
-----------------
Randomized Proteomic Stratified Phase III Study of Second-Line Erlotinib Versus Chemotherapy in Patients With Inoperable Non Small Cell Lung Cancer

Conditions
-----------------
Lung Cancer

Intervention / Treatment
-----------------
* Drug: docetaxel
* Drug: erlotinib hydrochloride
* Drug: pemetrexed disodium
* Genetic: fluorescence in situ hybridization
* Genetic: mutation analysis
* Genetic: proteomic profiling
* Other: immunohistochemistry staining method
* Other: laboratory biomarker analysis
* Other: matrix-assisted laser desorption/ionization time of flight mass spectrometry
* Procedure: breath test


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) Advanced NSCLC (stage IIIB or IV) Measurable disease Underwent previous treatment with 1 non-tyrosine kinase inhibitor as first-line therapy for advanced NSCLC No clinical evidence of uncontrolled brain metastases PATIENT CHARACTERISTICS: Caucasian ECOG performance status 0-2 Absolute granulocyte count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Bilirubin ≤ 1.5 times upper limit of normal (ULN) (≤ 2.5 times ULN in patients with known liver metastases) ALT or AST ≤ 3 times ULN (≤ 5 times ULN in patients with known liver metastases) Creatinine clearance ≥ 50 mL/min Not pregnant or nursing Able to comply with planned study procedures No multiple severe diseases that can compromise safety (cardiac and renal failure, peripheral neuropathy) No other malignancy (except for basal cell skin carcinoma) or pre-neoplastic condition requiring chemotherapeutic treatment PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 3 weeks since prior surgery or radiotherapy

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: Treatment
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: docetaxel|nan|
|Drug: erlotinib hydrochloride|nan|
|Drug: pemetrexed disodium|nan|
|Genetic: fluorescence in situ hybridization|nan|
|Genetic: mutation analysis|nan|
|Genetic: proteomic profiling|nan|
|Other: immunohistochemistry staining method|nan|
|Other: laboratory biomarker analysis|nan|
|Other: matrix-assisted laser desorption/ionization time of flight mass spectrometry|nan|
|Procedure: breath test|nan|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  |  | 
| Overall response rate according to RECIST criteria |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
recurrent non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer