A Study of Tarceva (Erlotinib) in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (TRIGGER)

Phase II, Open-label Study of Erlotinib (Tarceva®) Treatment in Patients With Locally Advanced or Metastatic Non-small-cell Lung Cancer Who Present Activating Mutations in the Tyrosine Kinase Domain of the Epidermal Growth Factor Receptor (EGFR) - (TRIGGER)

This single-arm, open-label study evaluated the efficacy and safety of Tarceva (erlotinib) in participants with locally advanced or metastatic non-small cell lung cancer. Participants received daily oral doses of 150 mg Tarceva. The anticipated time on study treatment was 12 months.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica A
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40133
      • Ospedale Bellaria; U.O. Oncologia Medica
    • Modena, Emilia-Romagna, Italy, 41100
      • A.O. Universitaria Policlinico Di Modena; Ematologia
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Istituto Regina Elena; Oncologia Medica A
  • Lombardia
    • Milano, Lombardia, Italy, 20141
      • Istituto Europeo di Oncologia
    • Rozzano, Lombardia, Italy, 20089
      • Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
  • Sicilia
    • Catania, Sicilia, Italy, 95122
      • Az Ospedaliera Nuovo Garibaldi Quartiere Nesima; Oncologia Medica
    • Palermo, Sicilia, Italy, 90127
      • Policlinico P. Giaccone; Istituto Di Oncologia, Clinica Medica 1
  • Toscana
    • Pisa, Toscana, Italy, 56124
      • A.O. Universitaria Pisana-Ospedale Cisanello; Dipartimento Cardio Toracico-Pneumologia Ii
  • Umbria
    • Perugia, Umbria, Italy, 06156
      • Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica

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, >/=18 years of age
• Locally advanced or metastatic non-small cell lung cancer
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Life expectancy over >/=12 weeks
• Adequate hematological, liver, or kidney function

Exclusion Criteria:

• Previous therapy against epidermal growth factor receptor for metastatic disease
• Treatment with investigational drug during the 3 weeks before enrollment
• History of neoplasm
• Patients with symptomatic cerebral metastases
• Unstable systemic disease

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: Single Arm	Drug: erlotinib; 150 mg orally once a day for 12 months; Other Names: Tarceva

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Disease Progression or Death at 12 Months After Baseline	According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), progressive disease (PD) was defined as at least a 20 percent (%) 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.	12 months
Progression-Free Survival (PFS)	PFS was defined as the time from baseline to the date of first occurrence of disease progression or death. According to RECIST v1.1, 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. PFS was assessed using Kaplan-Meier method.	Up to 1 year after enrollment of the last participant (maximum up to 27 months)
Probability of Being Progression Free 12 Months After Baseline	According to RECIST v1.1, 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.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Died		Every 8 weeks during treatment, after discontinuation participants were followed for up to 1 year after enrollment of the last participant (maximum up to 27 months)
Overall Survival (OS)	OS was defined as the time from randomization to the date of death due to any cause. OS was assessed using Kaplan-Meier method.	Every 8 weeks during treatment, after discontinuation participants were followed for up to 1 year after enrollment of the last participant (maximum up to 27 months)
Percentage of Participants With a Response by Best Overall Response	Tumor response was assessed according to RECIST v1.1. Complete response (CR): complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes must decrease to normal (short axis less than 10 mm), with no new lesions. Partial response (PR): greater than or equal to (>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease, and no new lesions. PD: >=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, appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Stable disease (SD): not qualifying for CR, PR, or PD.	Baseline up to disease progression or end of study (up to 12 Months)
Percentage of Participants With Objective Response	Objective response was defined as the percentage of participants with CR or PR as best overall response by RECIST v1.1. To be assigned the status of PR or CR, changes in tumor measurements were to be confirmed by repeated assessments no less than 4 weeks after the criteria for response were first met. CR was defined as complete disappearance of all target lesions and non-target disease, with exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than 10 mm), with no new lesions. PR was defined as >=30% decrease under baseline of sum of diameters of all target lesions. The short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions. No unequivocal progression of non-target disease, and no new lesions. Participants with no tumor assessment after start of study treatment were considered as non-responders. The percentage of participants with response is presented.	Baseline up to disease progression or end of study (up to 12 Months)
Percentage of Participants Achieving CR, PR, or SD as Best Overall Response	The Disease Control Rate was defined as the percentage of participants who had CR or PR or SD as Best Overall Response achieved within the time between the first drug administration and documented disease progression or end of study. According to RECIST v1.1, CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than 10 mm), with no new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease, and no new lesions. SD was defined as not qualifying for CR, PR, or PD.	Baseline up to disease progression or end of study (up to 12 Months)
Percentage of Participants With Primary and Secondary Resistance	Primary resistance: participants did not reach SD or PR or CR before going to PD. Secondary resistance: participants experienced PD after having reached SD or PR or CR at least once. CR: complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes must decrease to normal (short axis less than 10 mm), with no new lesions. PR: >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease, and no new lesions. PD: >=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, appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.	Baseline up to disease progression (up to 12 Months)
Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Mutation by Mutation Type	EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR mutation was determined in liquid biopsies by reverse transcriptase-polymerase chain reaction (RT-PCR /Cobas).	Baseline, At progression of disease (up to 12 Months)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2011
• Primary Completion (Actual): June 30, 2013
• Study Completion (Actual): January 31, 2017

Study Registration Dates

• First Submitted: June 21, 2011
• First Submitted That Met QC Criteria: June 21, 2011
• First Posted (Estimate): June 23, 2011

Study Record Updates

• Last Update Posted (Actual): January 23, 2018
• Last Update Submitted That Met QC Criteria: December 21, 2017
• Last Verified: December 1, 2017

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: ML25514