Erlotinib Versus Pemetrexed as Second-Line Therapy in Treating Patients With Advanced Lung Adenocarcinoma

Study Overview
=================
Brief Summary
-----------------
Both pemetrexed and erlotinib are second-line treatment options for patients with advanced non-small cell lung cancer. It is controversial that whether it is necessary to detect epidermal growth factor receptor (EGFR) mutation status for the EGFR-targeted therapy after the failure of standard chemotherapy. The role of EGFR gene copy number as a predictive marker remains controversial. Therefore, we investigate the efficacy of erlotinib and pemetrexed as second-line therapy in treating in patients with EGFR wild-type and EGFR FISH-positive advanced lung adenocarcinoma.

Detailed Description
-----------------
Standard first-line treatment for advanced-stage non-small cell lung cancer (NSCLC) usually consists of platinum-based doublet chemotherapy, but progression ultimately occurs for most patients. Second-line treatment options available to patients who suffer failure of first-line treatment include further chemotherapy (docetaxel and pemetrexed) or targeted therapy. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) show great efficacy in patients with advanced NSCLC with EGFR mutation. High EGFR gene copy number was associated with great sensitivity and prolonged progression-free survival of NSCLC from EGFR-TKIs. This phase II study was designed to assess the efficacy and safety of erlotinib compared with pemetrexed as second-line treatment for EGFR wild-type and EGFR FISH-positive lung adenocarcinoma.

Official Title
-----------------
A Randomized Phase II Trial of Erlotinib Versus Pemetrexed as Second-Line Therapy in Treating Patients With Advanced EGFR Wild-Type and EGFR FISH-Positive Lung Adenocarcinoma

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

Intervention / Treatment
-----------------
* Drug: Erlotinib
* Drug: Pemetrexed


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed Lung adenocarcinoma Wld-type EGFR Stage IIIB/IV Failure to prior chemotherapy Life expectancy of more than 3 months Tissue sample desired for genomic study Age ≥ 18 years Performance status (WHO) < 3 Adequate bone marrow function (absolute neutrophil count > 1000/mm^3, platelet count > 100000/mm^3, hemoglobin > 9gr/mm^3) Adequate liver (bilirubin < 1.5 times upper limit of normal and SGOT/SGPT < 2 times upper limit of normal) and renal function (creatinine < 2mg/dl) Presence of two-dimensional measurable disease. The measurable disease should not have been irradiated Informed consent Exclusion Criteria: Have previously received pemetrexed or TKIs Other concurrent uncontrolled illness

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erlotinib<br>Erlotinib at the dose of 150 mg orally once a day continually until progression. | Drug: Erlotinib<br>* 150 mg Given orally<br>* Other names: Tarceva;|
| Experimental: Pemetrexed<br>Pemetrexed at the dose of 500mg/m2 IV infusion every 3 weeks until progression. | Drug: Pemetrexed<br>* 500mg/m2 Given IV<br>* Other names: ALIMTA;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | From the date of randomization to the date of tumour progression or death from any cause, assessed until at least 12 months after randomization. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Tumor Response | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | From the date of randomization, assessed every 6 weeks, until at least 12 months after randomization. | 
| Overall Survival |  | From date of randomization until the date of death from any cause, assessed until at least 12 months after randomization. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cancer, Non-small-cell lung cancer, Adenocarcinoma, EGFR gene mutation, Chemotherapy, Pemetrexed, Erlotinib