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

Tracking Information

• First Submitted Date: April 26, 2011
• First Posted Date: April 27, 2011
• Results First Submitted Date: February 5, 2015
• Results First Posted Date: February 24, 2015
• Last Update Posted Date: February 24, 2015
• Study Start Date: March 2011
• Actual Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 5, 2015)

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.

• Original Primary Outcome Measures (submitted: April 26, 2011): Progression-free survival (tumor assessments according to RECIST criteria) [ Time Frame: approximately 21 months ]

Current Secondary Outcome Measures (submitted: February 5, 2015)

• 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.
• 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.
• 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.
• 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.
• Safety: Incidence of Adverse Events [ Time Frame: 36 months ]
• Quality of Life: Functional Assessment of Chronic Illness Therapy - Lung (FACIT-L) Questionnaire [ Time Frame: approximately 21 months ]

Original Secondary Outcome Measures (submitted: April 26, 2011)

• Objective response rate (complete response + partial response) [ Time Frame: approximately 21 months ]
• Disease control rate (complete response + partial response + stable disease) [ Time Frame: approximately 21 months ]
• Duration of response [ Time Frame: approximately 21 months ]
• Overall survival [ Time Frame: 36 months ]
• Safety: Incidence of adverse events [ Time Frame: 36 months ]
• Quality of life: Functional Assessment of Chronic Illness Therapy - Lung (FACIT-L) questionnaire [ Time Frame: approximately 21 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer

Intervention

• Drug: Erlotinib
  Erlotinib was supplied as tablets.
  Other Name: Tarceva
• Drug: Chemotherapy
  Cisplatin and gemcitabine were locally sourced with commercial products.

Study Arms

• Experimental: Erlotinib
  Participants received erlotinib 150 mg orally once daily until progressive disease or unacceptable toxicity.
  Intervention: Drug: Erlotinib
• 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.
  Intervention: Drug: Chemotherapy

Publications *

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 3, 2014): 217
• Original Estimated Enrollment (submitted: April 26, 2011): 150
• Actual Study Completion Date: April 2014
• Actual Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China, Malaysia, Philippines

Administrative Information

• NCT Number: NCT01342965
• Other Study ID Numbers: YO25121
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Disclosures Group, Hoffmann-La Roche
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: February 2015