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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01342965
First received: April 26, 2011
Last updated: February 5, 2015
Last verified: February 2015
  Purpose

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 Intervention Phase
Non-Small Cell Lung Cancer
Drug: Erlotinib
Drug: Chemotherapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Investigator-assessed Duration of Progression-free Survival [ Time Frame: Baseline to the data cut-off date of 20 Jul 2012 (1 year, 4 months) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to the data cut-off date of 19 Nov 2012 (1 year, 8 months) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Quality of Life: Functional Assessment of Chronic Illness Therapy - Lung (FACIT-L) Questionnaire [ Time Frame: approximately 21 months ] [ Designated as safety issue: No ]

Enrollment: 217
Study Start Date: March 2011
Study Completion Date: April 2014
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01342965

Locations
China
Beijing, China, 100071
Beijing, China, 101149
Changchun, China, 130012
ChongQing, China, 400042
Chongqing, China, 400038
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, Malaysia, 46150
Petaling Jaya, Selangor, Malaysia, 46050
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

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01342965     History of Changes
Other Study ID Numbers: YO25121
Study First Received: April 26, 2011
Results First Received: February 5, 2015
Last Updated: February 5, 2015
Health Authority: China: Ministry of Health

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Cisplatin
Erlotinib
Gemcitabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2015