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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01310036

Enrollment

208

Registered

2011-03-07

Start date

2011-04-30

Completion date

2016-12-30

Last updated

2018-09-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Non-Squamous Non-Small Cell Lung Cancer

Brief summary

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.

Interventions

DRUGErlotinib

Erlotinib 150 mg was administered orally daily until disease progression or unacceptable toxicity.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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)

Design outcomes

Primary

Measure	Time frame	Description
Progression-free Survival Per RECIST, v. 1.1 (PFS1)	Approximately 68 months	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.

Secondary

Measure	Time frame	Description
Objective Response Rate (ORR) for All Participants and Participants With EGFR Mutation E19del or L858R	Approximately 68 months	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.
Disease Control Rate (DCR) for All Participants and Participants With EGFR Mutation E19del or L858R	Approximately 68 months	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.
Progression-free Survival for Participants With EGFR Mutation E19del or L858R Per RECIST, v. 1.1 (PFS1)	Approximately 68 months	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.
Progression-free Survival Per Investigator (PFS2)	Approximately 68 months	PFS2 was defined as time from first study dose to off-erlotinib progressive disease (PD), assessed by the investigator based on overall clinical evaluation.
Number of Participants With Adverse Events	Approximately 68 months	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.
Correlation Between EGFR Mutations in Plasma and Clinical Outcome (ORR/PFS/OS)	Approximately 68 months	This outcome measure was not assessed.
Overall Survival (OS) for All Participants and Participants With EGFR Mutation E19del or L858R	Approximately 68 months	OS was defined as the time from baseline to the date of death from any cause.

Countries

Hong Kong, South Korea, Taiwan, Thailand

Participant flow

Participants by arm

Arm	Count
Erlotinib Erlotinib 150 mg daily	207
Total	207

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Administrative/other	10
Overall Study	Adverse event or intercurrent illness	12
Overall Study	Death	1
Overall Study	Progression of Disease	164
Overall Study	Refused Treatment/Did not Cooperate	4
Overall Study	Withdrew Consent	11

Baseline characteristics

Characteristic	Erlotinib
Age, Continuous	61.3 years STANDARD_DEVIATION 11.56
Sex: Female, Male Female	129 Participants
Sex: Female, Male Male	78 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	206 / 207
serious Total, serious adverse events	59 / 207

Outcome results

Primary

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.