Back to resultsA Study of Erlotinib (Tarceva) Versus Gemcitabine/Cisplatin as First-line Treatment in Patients With Non-small Cell Lung Cancer With EGFR Mutations
Primary Purpose
Non-Small Cell Lung Cancer
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Erlotinib
Chemotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Non-Small Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria:
- Adult participants, ≥ 18 years of age.
- Locally advanced or recurrent (stage IIIB) or metastatic (stage IV) non-small cell lung cancer.
- Presence of epidermal growth factor receptor (EGFR) mutations in tumours.
- Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria.
- European Cooperative Oncology Group (ECOG) performance status ≤ 2.
Exclusion Criteria:
- Prior exposure to agents directed at the human epidermal receptor (HER) axis (eg, but not limited to erlotinib, gefitinib, cetuximab, or trastuzumab).
- Prior chemotherapy or systemic anti-neoplastic therapy for advanced disease.
- Lack of physical integrity of the upper gastrointestinal tract, or malabsorption syndrome, or inability to take oral medication, or active gastroduodenal ulcer disease.
- Any inflammatory changes of the surface of the eye.
- ≥ Grade 2 peripheral neuropathy.
- History of any other malignancies within 5 years, except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer.
- Brain metastasis or spinal cord compression that has not yet been definitely treated with surgery and/or radiation, or treated but without evidence of stable disease for at least 2 months.
- Human immunodeficiency virus (HIV) infection.
- Pregnant, nursing, or lactating women.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Erlotinib
Chemotherapy
Arm Description
Participants received erlotinib 150 mg orally once daily until progressive disease or unacceptable toxicity.
Participants received gemcitabine 1250 mg/m^2 intravenously (IV) on Days 1 and 8 and cisplatin 75 mg/m^2 IV on Day 1 of every 3 week cycle until disease progression, unacceptable toxicity, or a total of 4 cycles, whichever came first.
Outcomes
Primary Outcome Measures
Investigator-assessed Duration of Progression-free Survival
The duration of progression-free survival was defined as the time from randomization to disease progression (PD) or death from any cause, whichever occurs first. PD was defined as: (1) 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. (2) An unequivocal progression of existing non-target lesions. When the patient has measurable disease, the overall tumor burden must have increased sufficiently to merit discontinuation of therapy. When the patient has only non-measurable disease, the increase in overall disease burden should be comparable in magnitude to the increase that would be required to declare PD for measurable disease. (3) The appearance of new malignant lesions.
Secondary Outcome Measures
Percentage of Responders as Assessed by the Investigator
A responder was defined as a participant with either a complete response (CR) or a partial response (PR), as determined using the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. A CR was defined as: (1) The disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to < 10 mm. (2) The disappearance of all non-target lesions and normalization of tumor marker levels. All lymph nodes must be non-pathological in size (< 10 mm in the short axis). A PR was defined as: (1) At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. (2) The persistence of 1 or more non-target lesion(s) and/or maintenance of tumor marker levels above normal limits.
Percentage of Participants With Disease Control
A participant with disease control was defined as a participant with either a complete response (CR), a partial response (PR), or stable disease (SD), as determined using RECIST v1.1. A CR was defined as the disappearance of all target lesions (TL). A PR was defined as at least a 30% decrease in the sum of the longest diameter of TLs taking as reference the Baseline sum longest diameter (SLD). 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 SLD since treatment started. For non-TLs, SD was defined as the persistence of 1 or more lesions. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since treatment started or the unequivocal progression of existing non-TLs. A SLD for all TLs will be calculated and reported as the Baseline SLD.
Duration of Response
Duration of response was defined as the time from the first documented complete response (CR) or partial response (PR) to the first documented disease progression (PD) or death, whichever occurs first. A CR was defined as the disappearance of all target lesions (TL). A PR was defined as at least a 30% decrease in the sum of the longest diameter (SLD) of TLs taking as reference the Baseline SLD. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since treatment started or the unequivocal progression of existing non-TLs.
Overall Survival
Overall survival was defined as the time from the date of randomization to the date of death from any cause.
Safety: Incidence of Adverse Events
Quality of Life: Functional Assessment of Chronic Illness Therapy - Lung (FACIT-L) Questionnaire
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01342965
Brief Title
A Study of Erlotinib (Tarceva) Versus Gemcitabine/Cisplatin as First-line Treatment in Patients With Non-small Cell Lung Cancer With EGFR Mutations
Official Title
A Multicenter, Open-label, Randomized Phase III Study to Evaluate the Efficacy and Safety of Erlotinib (Tarceva®) Versus Gemcitabine/Cisplatin as the First-line Treatment for Stage IIIB/IV Non-small Cell Lung Cancer (NSCLC) Patients With Mutations in the Tyrosine Kinase Domain of Epidermal Growth Factor Receptor (EGFR) in Their Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
February 2015
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
July 2012 (Actual)
Study Completion Date
April 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
Brief Summary
This open-label, randomized, parallel arm study assessed the efficacy and safety of Tarceva (erlotinib) versus gemcitabine/cisplatin combination chemotherapy as first-line treatment in patients with stage IIIB/IV non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations in their tumours. Patients were randomized to receive either Tarceva 150 mg orally daily or 3-week cycles of gemcitabine 1250 mg/m^2 intravenously (iv) on Days 1 and 8 plus cisplatin 75 mg/m^2 iv on Day 1.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
217 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Erlotinib
Arm Type
Experimental
Arm Description
Participants received erlotinib 150 mg orally once daily until progressive disease or unacceptable toxicity.
Arm Title
Chemotherapy
Arm Type
Active Comparator
Arm Description
Participants received gemcitabine 1250 mg/m^2 intravenously (IV) on Days 1 and 8 and cisplatin 75 mg/m^2 IV on Day 1 of every 3 week cycle until disease progression, unacceptable toxicity, or a total of 4 cycles, whichever came first.
Intervention Type
Drug
Intervention Name(s)
Erlotinib
Other Intervention Name(s)
Tarceva
Intervention Description
Erlotinib was supplied as tablets.
Intervention Type
Drug
Intervention Name(s)
Chemotherapy
Intervention Description
Cisplatin and gemcitabine were locally sourced with commercial products.
Primary Outcome Measure Information:
Title
Investigator-assessed Duration of Progression-free Survival
Description
The duration of progression-free survival was defined as the time from randomization to disease progression (PD) or death from any cause, whichever occurs first. PD was defined as: (1) 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. (2) An unequivocal progression of existing non-target lesions. When the patient has measurable disease, the overall tumor burden must have increased sufficiently to merit discontinuation of therapy. When the patient has only non-measurable disease, the increase in overall disease burden should be comparable in magnitude to the increase that would be required to declare PD for measurable disease. (3) The appearance of new malignant lesions.
Time Frame
Baseline to the data cut-off date of 20 Jul 2012 (1 year, 4 months)
Secondary Outcome Measure Information:
Title
Percentage of Responders as Assessed by the Investigator
Description
A responder was defined as a participant with either a complete response (CR) or a partial response (PR), as determined using the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. A CR was defined as: (1) The disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to < 10 mm. (2) The disappearance of all non-target lesions and normalization of tumor marker levels. All lymph nodes must be non-pathological in size (< 10 mm in the short axis). A PR was defined as: (1) At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. (2) The persistence of 1 or more non-target lesion(s) and/or maintenance of tumor marker levels above normal limits.
Time Frame
Baseline to the data cut-off date of 19 Nov 2012 (1 year, 8 months)
Title
Percentage of Participants With Disease Control
Description
A participant with disease control was defined as a participant with either a complete response (CR), a partial response (PR), or stable disease (SD), as determined using RECIST v1.1. A CR was defined as the disappearance of all target lesions (TL). A PR was defined as at least a 30% decrease in the sum of the longest diameter of TLs taking as reference the Baseline sum longest diameter (SLD). 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 SLD since treatment started. For non-TLs, SD was defined as the persistence of 1 or more lesions. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since treatment started or the unequivocal progression of existing non-TLs. A SLD for all TLs will be calculated and reported as the Baseline SLD.
Time Frame
Baseline to the data cut-off date of 19 Nov 2012 (1 year, 8 months)
Title
Duration of Response
Description
Duration of response was defined as the time from the first documented complete response (CR) or partial response (PR) to the first documented disease progression (PD) or death, whichever occurs first. A CR was defined as the disappearance of all target lesions (TL). A PR was defined as at least a 30% decrease in the sum of the longest diameter (SLD) of TLs taking as reference the Baseline SLD. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since treatment started or the unequivocal progression of existing non-TLs.
Time Frame
Baseline to the data cut-off date of 19 Nov 2012 (1 year, 8 months)
Title
Overall Survival
Description
Overall survival was defined as the time from the date of randomization to the date of death from any cause.
Time Frame
Baseline to the end of the study (3 years, 1 month)
Title
Safety: Incidence of Adverse Events
Time Frame
36 months
Title
Quality of Life: Functional Assessment of Chronic Illness Therapy - Lung (FACIT-L) Questionnaire
Time Frame
approximately 21 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult participants, ≥ 18 years of age.
Locally advanced or recurrent (stage IIIB) or metastatic (stage IV) non-small cell lung cancer.
Presence of epidermal growth factor receptor (EGFR) mutations in tumours.
Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria.
European Cooperative Oncology Group (ECOG) performance status ≤ 2.
Exclusion Criteria:
Prior exposure to agents directed at the human epidermal receptor (HER) axis (eg, but not limited to erlotinib, gefitinib, cetuximab, or trastuzumab).
Prior chemotherapy or systemic anti-neoplastic therapy for advanced disease.
Lack of physical integrity of the upper gastrointestinal tract, or malabsorption syndrome, or inability to take oral medication, or active gastroduodenal ulcer disease.
Any inflammatory changes of the surface of the eye.
≥ Grade 2 peripheral neuropathy.
History of any other malignancies within 5 years, except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer.
Brain metastasis or spinal cord compression that has not yet been definitely treated with surgery and/or radiation, or treated but without evidence of stable disease for at least 2 months.
Human immunodeficiency virus (HIV) infection.
Pregnant, nursing, or lactating women.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Beijing
ZIP/Postal Code
100071
Country
China
City
Beijing
ZIP/Postal Code
101149
Country
China
City
Changchun
ZIP/Postal Code
130012
Country
China
City
Chongqing
ZIP/Postal Code
400038
Country
China
City
ChongQing
ZIP/Postal Code
400042
Country
China
City
Fuzhou
ZIP/Postal Code
350014
Country
China
City
Guangzhou
ZIP/Postal Code
510080
Country
China
City
Hangzhou
ZIP/Postal Code
310016
Country
China
City
Nanjing
ZIP/Postal Code
210002
Country
China
City
Shanghai
ZIP/Postal Code
200030
Country
China
City
Shanghai
ZIP/Postal Code
200032
Country
China
City
Shanghai
ZIP/Postal Code
200433
Country
China
City
Shantou
ZIP/Postal Code
515041
Country
China
City
Wuhan
ZIP/Postal Code
430023
Country
China
City
Xi'an
ZIP/Postal Code
710061
Country
China
City
Kelantan
ZIP/Postal Code
16150
Country
Malaysia
City
Kuala Lumpur
ZIP/Postal Code
50603
Country
Malaysia
City
Kuala Lumpur
ZIP/Postal Code
59100
Country
Malaysia
City
Nilai
ZIP/Postal Code
71800
Country
Malaysia
City
Pahang
ZIP/Postal Code
25100
Country
Malaysia
City
Petaling Jaya, Selangor
ZIP/Postal Code
46050
Country
Malaysia
City
Petaling Jaya
ZIP/Postal Code
46150
Country
Malaysia
City
Pulau Pinang
ZIP/Postal Code
11600
Country
Malaysia
City
Davao
ZIP/Postal Code
8000
Country
Philippines
City
Desmarinas City
ZIP/Postal Code
4114
Country
Philippines
City
Manila
ZIP/Postal Code
1000
Country
Philippines
City
Quezon City
ZIP/Postal Code
1104
Country
Philippines
City
San Juan
ZIP/Postal Code
1500
Country
Philippines
12. IPD Sharing Statement
Citations:
PubMed Identifier
29654023
Citation
Wen F, Zheng H, Zhang P, Hutton D, Li Q. OPTIMAL and ENSURE trials-based combined cost-effectiveness analysis of erlotinib versus chemotherapy for the first-line treatment of Asian patients with non-squamous non-small-cell lung cancer. BMJ Open. 2018 Apr 13;8(4):e020128. doi: 10.1136/bmjopen-2017-020128.
Results Reference
derived
PubMed Identifier
26105600
Citation
Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, Lu S, Cheng Y, Han B, Chen L, Huang C, Qin S, Zhu Y, Pan H, Liang H, Li E, Jiang G, How SH, Fernando MCL, Zhang Y, Xia F, Zuo Y. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol. 2015 Sep;26(9):1883-1889. doi: 10.1093/annonc/mdv270. Epub 2015 Jun 23.
Results Reference
derived
Learn more about this trial
A Study of Erlotinib (Tarceva) Versus Gemcitabine/Cisplatin as First-line Treatment in Patients With Non-small Cell Lung Cancer With EGFR Mutations
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