Erlotinib or Placebo Following Chemoradiotherapy (Chemo/RT) in Stage III Non-Small Cell Lung Cancer (NSCLC)

Study Overview
=================
Brief Summary
-----------------
This is a national, randomized, web-based, double-blind study to determine whether erlotinib (Tarceva) compared to placebo improves progression-free survival (PFS) for patients with inoperable, stage III NSCLC following concurrent docetaxel, carboplatin and thoracic radiotherapy. We hypothesize that the introduction of this orally active, well-tolerated agent following concurrent chemoradiation and prior to the emergence of drug resistance will prolong the progression-free survival by 40% (10 months → 14 months).

Detailed Description
-----------------
The promising activity of erlotinib as a single agent in advanced refractory NSCLC along with its oral administration and favorable adverse event profile makes this agent an excellent candidate to incorporate into combined modality therapy in the early stages of lung cancer. Based on these data, erlotinib is an attractive novel approach to maintenance therapy in unresectable stage III NSCLC following completion of concomitant chemoradiation. Although, a subset of patients with unresectable stage III NSCLC will be long-term survivors following chemotherapy and thoracic radiation therapy, the vast majority relapse within the first year following therapy and eventually die from chemotherapy refractory disease. We hypothesize that the introduction of an potent tyrosine kinase inhibitor to the epidermal growth factor receptor following effective concomitant chemoradiotherapy with docetaxel and carboplatin will prolong the progression-free survival time for these patients.

Official Title
-----------------
A National Web-Based Randomized Phase III Study of Erlotinib or Placebo Following Concurrent Docetaxel, Carboplatin, and Thoracic Radiotherapy in Patients With Inoperable Stage III Non-Small Cell Lung Cancer (D0410).

Conditions
-----------------
NSCLC, Carcinoma, Non-Small-Cell Lung, Non-small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: Erlotinib (tarceva)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Unresectable, stage IIIA or IIIB NSCLC (measurable disease is not required) No evidence of metastatic disease No prior treatment Adequate organ function Adequate pulmonary function (FEV >= 1.0L or predicted FEV >0.8L) Exclusion Criteria: Metastasis Prior treatment Malignant pleural or pericardial effusion Peripheral neuropathy >= grade 2

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Erlotinib (Tarceva) 150mg: Erlotinib 150mg orally each day. Patients will be treated on a continuous, once daily oral dosing schedule until disease progression, withdrawal of consent, unacceptable adverse events, death or completion of 3 years of therapy. | Drug: Erlotinib (tarceva)<br>* Erlotinib 150mg orally each day. Patients will be treated on a continuous, once daily oral dosing schedule until disease progression, withdrawal of consent, unacceptable adverse events, death or completion of 3 years of therapy.<br>|
| Placebo Comparator: 2<br>Matched Placebo: Matched placebo orally each day. Patients will be treated on a continuous, once daily oral dosing schedule until disease progression, withdrawal of consent, unacceptable adverse events death or completion of 3 years of therapy. | Drug: Placebo<br>* Matched placebo orally each day. Patients will be treated on a continuous, once daily oral dosing schedule until disease progression, withdrawal of consent, unacceptable adverse events death or completion of 3 years of therapy.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression Free Survival is defined as time from randomization until documented disease progression or death from any cause. The Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.0) was used to determine disease progression. Irradiated target lesions were considered non-measurable disease. Symptomatic radiographic changes of irradiated non-measurable disease required pathologically confirmation or positive FDG-PET scan 6 months following completion of concurrent chemoradiation to be considered locoregional disease progression. Global deterioration of health status requiring discontinuation of treatment without objective evidence of progression was considered distant disease progression. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | From date of randomization until the date of death from any cause, assessed up to 50 months | 
| Percent of Participants Surviving 3 Years |  | 36 months | 
| Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Concurrent Chemoradiation | Number of participants with treatment-related serious adverse events (SAEs) observed in each SAE category for each arm relating to death, disability, life-threatening, hospitalization, and impairment/damage is reported. For participants with multiple SAEs, the SAE report having the strongest relationship to study drug is summarized. | 18 months | 
| Serious Adverse Event Profile Relating to Death, Disability, Life-threatening, Hospitalization, and Impairment/Damage for Erlotinib and Placebo | Number of participants with treatment-related serious adverse events (SAEs) observed in each SAE category for each arm relating to death, disability, life-threatening, hospitalization, and impairment/damage is reported. For participants with multiple SAEs, the SAE report having the strongest relationship to study drug is summarized. | 18 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Erlotinib, Tarceva, Web based, Stage III NSCLC