A Study of Tarceva (Erlotinib) as First Line Therapy in Participants With Non-Small Cell Lung Cancer Harbouring Epidermal Growth Factor Receptor (EGFR) Mutations

An Open-Label Multicenter Study of Erlotinib (Tarceva®) as First Line Therapy Until and Beyond RECIST Progression in NSCLC Patients Who Harbour EGFR Mutations

This open-label, single arm study will evaluate the safety and efficacy of Tarceva (erlotinib) as first-line therapy in participants with stage IV or recurrent non-small cell lung cancer who harbour epidermal growth factor receptor (EGFR) mutations. All participants will receive Tarceva 150 mg daily orally until disease progression or unacceptable toxicity occurs. At the investigator's discretion, participants may receive Tarceva beyond disease progression.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 208
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Princess Margaret Hospital; Oncology
  • Hong Kong, Hong Kong
    • Queen Elizabeth Hospital; Clinical Oncology
  • Shatin, Hong Kong
    • Prince of Wales Hosp; Dept. Of Clinical Onc
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Incheon, Korea, Republic of, 405-760
    • Gil Hospital. Gachon University
  • Seoul, Korea, Republic of, 120-752
    • Yonsei University Severance Hospital; Medical Oncology
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center; Medical Oncology
  • Seoul, Korea, Republic of, 06591
    • Seoul St Mary's Hospital
• Taiwan
  • Changhua, Taiwan, 500
    • Changhua Christian Hospital; Internal Medicine
  • Kaohsiung, Taiwan, 00833
    • Kaohsiung Chang Gung Memorial Hospital; Dept of Internal Medicine
  • Kaohsiung, Taiwan, 813
    • Veterans General Hospital; Internal Medicine
  • Taichung, Taiwan, 40447
    • China Medical University Hospital; Pulmonary and Critical Care Medicine
  • Taichung, Taiwan, 407
    • Taichung Veterans General Hospital; Dept of Internal Medicine
  • Tainan, Taiwan, 710
    • Chi-Mei Medical Centre; Hematology & Oncology
  • Tainan, Taiwan, 704
    • National Cheng Kung Uni Hospital; Dept of Hematology and Oncology
  • Taipei, Taiwan, 100
    • National Taiwan Uni Hospital; Internal Medicine
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital; Chest Dept , Section of Thoracic Oncology
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation - Linkou; Chest Dept
• Thailand
  • Bangkok, Thailand, 10400
    • Pramongkutklao Hospital; Medicine - Medical Oncology Unit
  • Bangkok, Thailand, 10330
    • Chulalongkorn Hospital; Medical Oncology
  • Songkhla, Thailand, 90110
    • Songklanagarind Hospital; Department of Internal Medicine, Division of Respiratory

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 participants, >/= 18 years of age
• Stage IV or recurrent non-small cell lung cancer (NSCLC)
• Presence of mutation(s) in exon 18 through exon 21 of epidermal growth factor receptor (EGFR), (except T790M single mutation only)
• Measurable disease (at least one lesion >= 10 mm in longest diameter)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Adequate hematological, renal and liver function

Exclusion Criteria:

• Patients with T790M single mutation only
• Prior exposure to agents directed at the human epidermal receptor (HER) axis, e.g. erlotinib, gefitinib, cetuximab, trastuzumab
• Prior chemotherapy or systemic anti-cancer therapy for advanced NSCLC disease
• Symptomatic or uncontrolled central nervous system (CNS) metastases
• Other malignancy within the last 5 years, except for carcinoma in situ of the cervix, or basal or squamous cell carcinoma of the skin, or surgically treated localized prostate cancer, or surgically treated ductal cell carcinoma in situ of the breast
• Any significant ophthalmologic abnormality
• Pre-existing parenchymal lung disease such as pulmonary fibrosis
• Use of coumarins (for anti-coagulation therapy the use of low molecular weight heparin is recommended instead)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Erlotinib; Erlotinib 150 mg daily	Drug: Erlotinib; Erlotinib 150 mg was administered orally daily until disease progression or unacceptable toxicity.; Other Names: Tarceva

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival Per RECIST, v. 1.1 (PFS1)	PFS1 was defined as time from first dose until documented progressive disease (PD), assessed per Response Evaluation Criteria in Solid Tumors RECIST, v. 1.1, or death from any cause, whichever occurred first. PD was defined as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; and the appearance of one or more new lesions.	Approximately 68 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival Per Investigator (PFS2)	PFS2 was defined as time from first study dose to off-erlotinib progressive disease (PD), assessed by the investigator based on overall clinical evaluation.	Approximately 68 months
Objective Response Rate (ORR) for All Participants and Participants With EGFR Mutation E19del or L858R	ORR was defined as the occurrence of either a confirmed complete (CR) or a partial response (PR, as a best overall response), as determined by RECIST, v. 1.1 criteria. CR was defined as disappearance of all target lesions. PR was defined as least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	Approximately 68 months
Disease Control Rate (DCR) for All Participants and Participants With EGFR Mutation E19del or L858R	DCR was defined as CR + PR + Stable disease (SD). CR was defined as disappearance of all target lesions. PR was defined as least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. PD was defined as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; and the appearance of one or more new lesions.	Approximately 68 months
Progression-free Survival for Participants With EGFR Mutation E19del or L858R Per RECIST, v. 1.1 (PFS1)	PFS1 was defined as time from first dose until documented progressive disease (PD), assessed per Response Evaluation Criteria in Solid Tumors RECIST, v. 1.1, or death from any cause, whichever occurred first. PD was defined as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; and the appearance of one or more new lesions.	Approximately 68 months
Overall Survival (OS) for All Participants and Participants With EGFR Mutation E19del or L858R	OS was defined as the time from baseline to the date of death from any cause.	Approximately 68 months
Number of Participants With Adverse Events	An adverse event is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug.	Approximately 68 months
Correlation Between EGFR Mutations in Plasma and Clinical Outcome (ORR/PFS/OS)	This outcome measure was not assessed.	Approximately 68 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Park K, Yu CJ, Kim SW, Lin MC, Sriuranpong V, Tsai CM, Lee JS, Kang JH, Chan KC, Perez-Moreno P, Button P, Ahn MJ, Mok T. First-Line Erlotinib Therapy Until and Beyond Response Evaluation Criteria in Solid Tumors Progression in Asian Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer: The ASPIRATION Study. JAMA Oncol. 2016 Mar;2(3):305-12. doi: 10.1001/jamaoncol.2015.4921.

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2011
• Primary Completion (Actual): February 14, 2014
• Study Completion (Actual): December 30, 2016

Study Registration Dates

• First Submitted: February 18, 2011
• First Submitted That Met QC Criteria: March 4, 2011
• First Posted (Estimate): March 7, 2011

Study Record Updates

• Last Update Posted (Actual): September 12, 2018
• Last Update Submitted That Met QC Criteria: September 10, 2018
• Last Verified: September 1, 2018

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: ML25637