A Study of Erlotinib (Tarceva) Versus Gemcitabine/Cisplatin as First-line Treatment in Patients With Non-small Cell Lung Cancer With EGFR Mutations

• ClinicalTrials.gov Identifier: NCT01342965
• Recruitment Status: Completed
• First Posted: April 27, 2011
• Results First Posted: February 24, 2015
• Last Update Posted: February 24, 2015
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

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.

Condition or disease	Intervention/treatment	Phase
Non-Small Cell Lung Cancer	Drug: Erlotinib; Drug: Chemotherapy	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 217 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: March 2011
• Actual Primary Completion Date: July 2012
• Actual Study Completion Date: April 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Erlotinib; Participants received erlotinib 150 mg orally once daily until progressive disease or unacceptable toxicity.	Drug: Erlotinib; Erlotinib was supplied as tablets.; Other Name: Tarceva
Active Comparator: Chemotherapy; 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.	Drug: Chemotherapy; Cisplatin and gemcitabine were locally sourced with commercial products.

Outcome Measures

Primary Outcome Measures :

1. Investigator-assessed Duration of Progression-free Survival [ Time Frame: Baseline to the data cut-off date of 20 Jul 2012 (1 year, 4 months) ]
   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 :

1. Percentage of Responders as Assessed by the Investigator [ Time Frame: Baseline to the data cut-off date of 19 Nov 2012 (1 year, 8 months) ]
   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.
2. Percentage of Participants With Disease Control [ Time Frame: Baseline to the data cut-off date of 19 Nov 2012 (1 year, 8 months) ]
   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.
3. Duration of Response [ Time Frame: Baseline to the data cut-off date of 19 Nov 2012 (1 year, 8 months) ]
   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.
4. Overall Survival [ Time Frame: Baseline to the end of the study (3 years, 1 month) ]
   Overall survival was defined as the time from the date of randomization to the date of death from any cause.
5. Safety: Incidence of Adverse Events [ Time Frame: 36 months ]
6. Quality of Life: Functional Assessment of Chronic Illness Therapy - Lung (FACIT-L) Questionnaire [ Time Frame: approximately 21 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

China

Beijing, China, 100071

Beijing, China, 101149

Changchun, China, 130012

Chongqing, China, 400038

ChongQing, China, 400042

Fuzhou, China, 350014

Guangzhou, China, 510080

Hangzhou, China, 310016

Nanjing, China, 210002

Shanghai, China, 200030

Shanghai, China, 200032

Shanghai, China, 200433

Shantou, China, 515041

Wuhan, China, 430023

Xi'an, China, 710061

Malaysia

Kelantan, Malaysia, 16150

Kuala Lumpur, Malaysia, 50603

Kuala Lumpur, Malaysia, 59100

Nilai, Malaysia, 71800

Pahang, Malaysia, 25100

Petaling Jaya, Selangor, Malaysia, 46050

Petaling Jaya, Malaysia, 46150

Pulau Pinang, Malaysia, 11600

Philippines

Davao, Philippines, 8000

Desmarinas City, Philippines, 4114

Manila, Philippines, 1000

Quezon City, Philippines, 1104

San Juan, Philippines, 1500

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01342965
• Other Study ID Numbers: YO25121
• First Posted: April 27, 2011
• Results First Posted: February 24, 2015
• Last Update Posted: February 24, 2015
• Last Verified: February 2015

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Erlotinib Hydrochloride; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents