A Study of Tarceva (Erlotinib) to Compare Two Different Doses in in Currently Smoking Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (CURRENTS)

Study Overview
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Brief Summary
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This prospective, double-blind, randomized study will evaluate the safety and efficacy of two dose levels of erlotinib [Tarceva] on progression-free survival, response and disease control rates and overall survival in patients with advanced or metastatic non-small cell lung cancer (NSCLC) after failure of first-line platinum-based chemotherapy. Patients must be current smokers and not intending to stop smoking during the study. Patients will be randomized to receive either 150 mg or 300 mg of study drug as single daily oral doses. Treatment will continue until disease progression.

Official Title
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A Prospective, Double-blind Randomized Phase III Study of 300 mg Versus 150 mg Erlotinib in Current Smokers With Locally Advanced or Metastatic NSCLC in Second-line Setting After Failure on Chemotherapy (CURRENTS)

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Erlotinib [Tarceva]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients aged ≥18 years inoperable, locally advanced (stage IIIB/IV) with supraclavicular lymph node metastases or malignant pleural or pericardial effusion) or metastatic (stage IV) non-small cell lung cancer (NSCLC) Disease must be characterized according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria Patients have received one prior platinum-based chemotherapy regimen for advanced NSCLC, but must have recovered from any treatment-related toxicity Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Life expectancy ≥12 weeks Current cigarette smoker (having smoked >100 cigarettes in entire lifetime and currently smoking on average ≥1 cigarette per day), not intending to stop during the study Exclusion Criteria: Prior antibody or small molecule therapy against Epidermal growth factor receptor (EGFR) Radiotherapy within 28 days prior to enrollment Received more than one line of chemotherapy for locally advanced/metastatic NSCLC (first-line maintenance chemotherapy after first-line platinum-based chemotherapy is allowed)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erlotinib 150 mg<br>Erlotinib 150 mg single daily oral dose until disease progression. | Drug: Erlotinib [Tarceva]<br>* Single daily oral dose<br>* Other names: Tarceva;|
| Experimental: Erlotinib 300 mg<br>Erlotinib 300 mg single daily oral dose until disease progression. | Drug: Erlotinib [Tarceva]<br>* Single daily oral dose<br>* Other names: Tarceva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS is defined as the time from randomization to the date of first occurrence of disease progression or death. For target lesions, Progressive Disease (PD) was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. | Randomization to Clinical Cutoff: 28 October 2013 (Up to 36.5 Months) | 
| Progression-Free Survival (PFS) at the End of Study | PFS is defined as the time from randomization to the date of first occurrence of disease progression or death. For target lesions, Progressive Disease (PD) was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. | Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS defined as the time from randomization to the date of death due to any cause. | Randomization to Clinical Cutoff: 28 October 2013 (Up to 36.5 months) | 
| Overall Response Rate (ORR) | Tumor response was assessed by the investigator using computer tomography (CT) or magnetic resonance imaging (MRI) scans according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A participant was defined as a responder if they sustained a complete response (CR) or partial response (PR) for at least 4 weeks during randomized treatment (confirmed response). Patients with no tumor assessment after the start of study treatment were to be considered as non-responders. The percentage of participants in each best response category is presented. | Randomization to Clinical Cutoff: 28 October 2013 (Up to 36.5 months) | 
| Disease Control Rate (DCR) | Tumor response was assessed by the investigator using computer tomography (CT) or magnetic resonance imaging (MRI) scans. Disease control rates were measured according to RECIST version 1.1 criteria. A participant was defined as having controlled disease if they sustained a Complete Response (CR) or Partial Response (PR) for at least 4 weeks during randomized treatment (confirmed response), or Stable Disease (SD) for at least 6 weeks. Patients with no tumor assessment after the start of study treatment were considered as having uncontrolled disease. The percentage of participants with Disease Control is presented. | Randomization to Clinical Cutoff: 28 October 2013 (Up to 36.5 months) | 
| Time to Progression (TTP) | Tumor response was assessed by the investigator using computer tomography (CT) or magnetic resonance imaging (MRI) scans according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. Time to progression (TTP) in weeks was defined as the time from randomization to the date of disease progression. Participants without event were censored at the date of the last tumor assessment when the patient was known to be progression free. | Randomization to Clinical Cutoff: 28 October 2013 (Up to 36.5 months) | 
| Number of Participants With Adverse Events (AEs) at the End of the Study | An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. Adverse Events in the following categories are presented: Adverse Events, Serious Adverse Events, AEs leading to withdrawal from treatment and AEs leading to death. | Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) | 
| Overall Survival (OS) at the End of Study | OS defined as the time from randomization to the date of death due to any cause. | Randomization to End of Study: 14 October 2010 - 7 February 2014 (Up to 39.8 months) |