A Study to Assess the Incidence of EGFR Mutation in Patients With Newly Diagnosed Locally Advanced or Metastatic Non-Small Cell Lung Cancer in the UK, And of Tarceva (Erlotinib) as First-Line Therapy in EGFR Mutation Positive Patients.

Assess the Incidence of Mutations in the Tyrosine Kinase Domain of the Endothelial Growth Factor Receptor in UK Patients With Newly Diagnosed Metastatic or Recurrent Non-small Cell Lung Cancer and to Investigate the Quality of Life of These Patients Undergoing First-line Therapy With Erlotinib.

This study will assess the prevalence of epidermal growth factor receptor (EGFR) mutations in newly diagnosed patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). Patients with positive EGFR mutation results will enter an open-label, single arm study to evaluate progression-free survival and quality of life with first-line Tarceva (erlotinib) therapy. Patients will receive Tarceva at a dose of 150 mg orally daily. Anticipated time on study treatment is until progressive disease or unacceptable toxicity occurs. Patients with negative EGFR mutation results will be offered treatment as per the centre's standard of care.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 688
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
  • Belfast, United Kingdom, BT47 6SB
  • Bradford, United Kingdom, BD9 6RJ
  • Brighton, United Kingdom, BN2 5BE
  • Chelsmford, United Kingdom, CM1 7ET
  • Colchester, United Kingdom, C03 3NB
  • Dudley, United Kingdom, DY1 2HQ
  • Glasgow, United Kingdom, G12 0YN
  • Grimsby, United Kingdom, DN33 2BA
  • London, United Kingdom, W6 8RF
  • London, United Kingdom, NW1 2PG
  • London, United Kingdom, N18 1QX
  • London, United Kingdom, NW3 2QG
  • London, United Kingdom, SW17 0QT
  • London, United Kingdom, DD1 9SY
  • Newtownards, United Kingdom, BT16 1RH
  • Portadown, United Kingdom, BT63 5QQ
  • Rhyl, United Kingdom, LL18 5UJ
  • Sutton in Ashfield, United Kingdom, NG17 4JL
  • Truro, United Kingdom, TR1 3LJ
  • Westcliffe-on-sea, United Kingdom, SS0 0RY
  • York, United Kingdom, BD20 6TD

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 (stage IIIB/IV) non-small cell lung cancer (NSCLC)
• ECOG performance status 0-3
• Treatment phase: histologically confirmed EGFR exon 19 deletion or exon 21 mutation in the diagnostic phase of the study
• Adequate haematological, liver and renal function
• Female patients must be postmenopausal, surgically sterile, or agree to use a barrier method of contraception
• Male patients must be surgically sterile or agree to use a barrier method of contraception

Exclusion Criteria:

• Previous treatment for NSCLC with chemotherapy or therapy against EGFR, either with antibody or small molecule (tyrosine kinase inhibitor)
• Symptomatic cerebral metastases
• Pregnant or lactating women
• Any other concomitant anti-cancer therapy (until disease progression and discontinuation of Tarceva therapy)

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 [Tarceva]; 150 mg daily, orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Tested Positive for EGFR Mutations	All participants newly diagnosed with recurrent or metastatic NSCLC were tested for EGFR exon 19 deletion or exon 21 mutations.	14 days
Percentage of Participants With EGFR Mutations by Subgroup	Incidence of EGFR mutations were summarized with respect to different subgroups as follows: (1) equals (=) Histopathology, (2) = Stage of disease, (3) = Age at consent, (4) = Gender, (5) = Race, (6) = Smoking history.	14 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Response by Best Objective Tumor Response	Best objective response was defined as the best response recorded from the start of treatment until disease progression/recurrence. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1". Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). Partial Response (PR): At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.	Screening, Day 1 of each 6 week visit starting from Visit 3 until PD, Death, Unacceptable Toxicity or Withdrawal of Consent up to 34 months
Probability of Being Alive and Free of Progression by Timepoint	Progression Free Survival (PFS) was defined as the interval (number of days) from the trial treatment start date to the earlier of the date of the first tumor response assessment of PD or the date of death by any cause. Participants who experienced neither of these events or who were lost to followup at the time of the analysis were censored at date of last contact. PFS was summarized according to the Kaplan-Meier method.	Months 0, 3, 6, 9, 12, 15, and 18
Survival Time in Months	Duration of time in months from Screening until Death due to any cause.	Baseline, Day 1 of each 6-week visit starting from Visit 3 until PD, Death, Unacceptable toxicity or Withdrawal of consent up to 34 months
Quality of Life Assessment Using EuroQol(EQ) 5D Visual Analog Score (VAS) Instrument	The EQ-5D contains a descriptive system that measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. The EQ-5D also contains a visual analog scale (EQ-VAS), which records the respondent's self-rated health status on a vertical graduated visual analog scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). A negative change indicates improvement.	Screening, Baseline and Final or Withdrawal Visit up to 34 months
Percentage of Participants With Problems With Mobility as Assessed Using the EQ-5D	The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. The participants were required to rate their mobility as the following categories: Category 1. I have no problems in walking about; Category 2. I have some problems in walking about; Category 3. I am confined to bed.	Baseline (Visit 1), Days 10 to 14 (Visit 2), Day 1 of every 6 weeks until PD, Death, Unacceptable toxicity or Withdrawal of consent up to 34 months
Percentage of Participants With Problems With Self-Care as Assessed Using the EQ-5D	The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. The participants were required to rate their self-care as the following categories: Category 1. I have no problems with self-care; Category 2. I have some problems washing or dressing myself; Category 3. I am unable to wash or dress myself.	Baseline (Visit 1), Days 10 to 14 (Visit 2), Day 1 of every 6 weeks until PD, Death, Unacceptable toxicity or Withdrawal of consent up to 34 months
Percentage of Participants With Problems With Usual Activities as Assessed Using the EQ-5D	The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. The participants were required to rate their ability to perform usual activities as the following categories: Category 1. I have no problems with performing my usual activities; Category 2. I have some problems with performing my usual activities; Category 3. I am unable to perform my usual activities.	Baseline (Visit 1), Days 10 to 14 (Visit 2), Day 1 of every 6 weeks until PD, Death, Unacceptable toxicity or Withdrawal of consent up to 34 months
Percentage of Participants With Pain/Discomfort as Assessed Using the EQ-5D	The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. The participants were required to rate their pain as the following categories: Category 1. I have no pain or discomfort; Category 2. I have moderate pain or discomfort; Category 3. I have extreme pain or discomfort.	Baseline (Visit 1), Days 10 to 14 (Visit 2), Day 1 of every 6 weeks until PD, Death, Unacceptable toxicity or Withdrawal of consent up to 34 months
Percentage of Participants With Anxiety/Depression as Assessed Using the EQ-5D	The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. The participants were required to rate their pain as the following categories: Category 1. I am not anxious or depressed; Category 2. I am moderately anxious or depressed; Category 3.I am extremely anxious or depressed.	Baseline (Visit 1), Days 10 to 14 (Visit 2), Day 1 of every 6 weeks until PD, Death, Unacceptable toxicity or Withdrawal of consent up to 34 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: November 29, 2010
• First Submitted That Met QC Criteria: November 29, 2010
• First Posted (Estimate): November 30, 2010

Study Record Updates

• Last Update Posted (Estimate): March 14, 2016
• Last Update Submitted That Met QC Criteria: February 16, 2016
• Last Verified: February 1, 2016

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: ML25279; 2010-021120-96