Genotype-Driven Treatment of Advanced Non-small Cell Lung Cancer Based on mRNA Expression of ERCC1 & RRM1 as First-line Chemotherapy

Study Overview
=================
Brief Summary
-----------------
This is a prospective phase II trial, in patients with unresectable or metastatic NSCLC using chemotherapy regimens which will be defined according to the mRNA expression of ERCC1 and RRM1 of the tumor cells.

Conditions
-----------------
Non-small Cell Lung Carcinoma

Intervention / Treatment
-----------------
* Drug: chemotherapy
* Drug: chemotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed unresectable advanced or metastatic non-small cell lung cancer (NSCLC) (stage IIIB or IV) Chemotherapy naïve patient (Previous adjuvant or neoadjuvant chemotherapy allowed if the last dose was administered equal to or greater than 6 months ago.) Age > 18 Performance status 0 to 2 by Eastern Cooperative Oncology Group (ECOG) criteria At least one measurable lesion by Response Evaluation Criteria In Solid Tumors (RECIST) Adequate organ functions (assessed within 14 days of starting treatment) 1) Bone marrow: Absolute neutrophil count ≥ 1,500/mm³, Platelet count ≥ 100,000/mm³, Hemoglobin ≥ 9.0 mg/dL 2) Liver: Total bilirubin ≤ 1.5 x ULN; aspartic transaminase (AST) and alanine transaminase (ALT), alkaline phosphatase(ALP) ≤ 2.5 x ULN 3) Kidney: Serum creatinine ≤ 1.5 x ULN Signed informed consent document Exclusion Criteria: Clinically significant serious illness or medical condition (infection) Prior systemic chemotherapy or immunotherapy for advanced NSCLC. Presence of uncontrolled brain or leptomeningeal metastases Prior radiotherapy within 3 weeks of starting treatment Peripheral neuropathy equal to or greater than grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) v4.0 Pregnant or lactating Absolute contraindication of corticosteroid use Patients with a history of severe hypersensitivity reaction to docetaxel, carboplatin, vinorelbine or gemcitabine

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
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Genomic-driven dual agent chemotherapy Chemotherapy will consist of the assigned two drugs according to ERCC1 and RRM1 mRNA expression level A1: docetaxel + vinorelbine (DV) A2: gemcitabine + vinorelbine (GV) A3: docetaxel + carboplatin (DC) A4: gemcitabine + carboplatin (GC) | Drug: chemotherapy<br>* A1: docetaxel 60mg/m2 on Day 1 vinorelbine 20mg/m2 on Day 1 and Day 8 (DV) A2: gemcitabine 1000mg/m2 on Day 1 vinorelbine 25mg/m2 on Day 1 and Day 8 (GV) A3: docetaxel 75mg/m2 on Day 1 carboplatin AUC5 on Day 1 (DC) A4: gemcitabine 1000mg/m2 on Day 1 and 8 carboplatin AUC5 on Day 1 (GC)<br>* Other names: Gemcitabine: Gemzar;|
| Active Comparator: Arm B<br>standard of care All control arm patients received standard platinum-based doublet chemotherapy with docetaxel plus carboplatin | Drug: chemotherapy<br>* Drug: Docetaxel 75mg/m2 IV on Day 1 Drug: Carboplatin AUC5 IV on Day 1<br>* Other names: Carboplatin: Carplan;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall Response Rate | ORR was assessed by tumor response evaluation according to RECIST 1.1 at every 8 weeks. Tumor assessments will continue about every 8 weeks until disease progression or initiation of subsequent anticancer treatment. (If PR or CR was first documented, confirmation assessment was done between 4 weeks and 8 weeks) | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival |  | up to 4 years | 
| overall survival |  | up to 4 years | 
| duration of response |  | up to 4 years | 
| disease control rate |  | up to 4 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
on-small cell lung carcinoma, chemotherapy naive patient