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)

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)

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.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Erlotinib [Tarceva]

• Study Type: Interventional
• Enrollment (Actual): 315
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100071
  • Changchun, China, 130012
  • Chengdu, China, 610041
  • Fuzhou, China, 350014
  • Guangzhou, China, 510030
  • Nanjing, China, 210009
  • Nanning, China, 530021
  • Shanghai, China, 200433
  • Shanghai, China, 200030
  • Shenyang, China, 110001
  • Tianjin, China, 300060
  • Wuhan, China, 430030
• Denmark
  • Hillerod, Denmark, 3400
  • København, Denmark, 2100
  • Naestved, Denmark, 4700
  • Roskilde, Denmark, 4000
• Egypt
  • Cairo, Egypt, 11796
  • Cairo, Egypt
• France
  • Caen, France, 14076
  • Limoges, France, 87042
  • Marseille, France, 13915
  • Paris, France, 75014
  • Paris, France, 75908
  • Paris, France, 75674
  • Pontoise, France, 95300
• Germany
  • Berlin, Germany, 13125
  • Berlin, Germany, 14165
  • Essen, Germany, 45122
  • Gauting, Germany, 82131
  • Grosshansdorf, Germany, 22927
  • Hannover, Germany, 30625
  • Hannover, Germany, 30659
  • Immenhausen, Germany, 34376
  • Lostau, Germany, 39291
  • München, Germany, 81925
  • Nürnberg, Germany, 90419
  • Rheine, Germany, 48431
  • Villingen-Schwenningen, Germany, 78052
  • Wuerselen, Germany, 52146
  • Wuppertal, Germany, 42283
• Netherlands
  • Amsterdam, Netherlands, 1007 MB
  • Breda, Netherlands, 4818 CK
  • Nieuwegein, Netherlands, 3435 CM
  • Zwolle, Netherlands, 8011 JW
• Spain
  • Barcelona, Spain, 08035
  • Barcelona, Spain, 08041
  • Madrid, Spain, 28040
  • Madrid, Spain, 28041
  • Malaga, Spain, 29010
  • Sevilla, Spain, 41013
  • Valencia, Spain, 46009
  • Barcelona
    • Sabadell, Barcelona, Barcelona, Spain, 08208
• Switzerland
  • Baden, Switzerland, 5404
  • Basel, Switzerland, 4031
  • Bern, Switzerland, 3011
  • Fribourg, Switzerland, 1708
• Turkey
  • Ankara, Turkey, 06200
  • Ankara, Turkey, 06000
  • Eskisehir, Turkey, 26480
  • Gaziantep, Turkey, 27310
  • Izmir, Turkey, 35340
  • Izmir, Turkey, 35110
  • Konya, Turkey, 42050

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Erlotinib 150 mg; Erlotinib 150 mg single daily oral dose until disease progression.	Drug: Erlotinib [Tarceva]; Single daily oral dose; Other Names: Tarceva
Experimental: Erlotinib 300 mg; Erlotinib 300 mg single daily oral dose until disease progression.	Drug: Erlotinib [Tarceva]; Single daily oral dose; Other Names: Tarceva

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: August 16, 2010
• First Submitted That Met QC Criteria: August 16, 2010
• First Posted (Estimate): August 18, 2010

Study Record Updates

• Last Update Posted (Estimate): August 19, 2015
• Last Update Submitted That Met QC Criteria: July 23, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: MO22162; 2010-018476-24 (EudraCT Number)