Gefitinib Versus Vinorelbine/Platinum as Adjuvant Treatment in Stage II-IIIA(N1-N2) NSCLC With EGFR Mutation (ADJUVANT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Guangdong Association of Clinical Trials
Sponsor:
Collaborators:
Guangdong General Hospital
First Affiliated Hospital, Sun Yat-Sen University
Sun Yat-sen University
Jilin Provincial Tumor Hospital
Liaoning Tumor Hospital & Institute
China Medical University, China
Chinese PLA General Hospital
Peking Union Medical College Hospital
Peking University People's Hospital
Beijing Chest Hospital
The 309 Hospital of People's Liberation Army
Beijing Cancer Hospital
Peking University First Hospital
Tianjin Medical University Cancer Institute and Hospital
Qingdao University
Jiangsu Cancer Institute & Hospital
The First Affiliated Hospital of Soochow University
Fudan University
Shanghai Pulmonary Hospital, Shanghai, China
Zhejiang Cancer Hospital
Zhejiang University
Wuhan Union Hospital, China
Tongji Hospital
West China Hospital
Tang-Du Hospital
Information provided by (Responsible Party):
Yi-Long Wu, Guangdong Association of Clinical Trials
ClinicalTrials.gov Identifier:
NCT01405079
First received: July 26, 2011
Last updated: September 5, 2013
Last verified: September 2013
  Purpose

Activating somatic mutations of the tyrosine kinase domain of epidermal growth factor receptor (EGFR) have been characterized in a subset of patients with advanced NSCLC.The EGFR mutation rate was 30% in Chinese Non-small Cell Lung Cancer(NSCLC). Patients harboring these mutations in their tumors show excellent response to EGFR tyrosine kinase inhibitors (EGFR-TKIs). This randomized phase III trial is studying gefitinib to see how well it works compared to cisplatin-based chemotherapy in treating patients who have undergone surgery for stage II-IIIA(N1-N2) NSCLC with EGFR activating mutation in Asian population.


Condition Intervention Phase
Non-small Cell Lung Cancer
Drug: Gefitinib
Drug: Vinorelbine/Cisplatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A National, Multi Center, Randomized, Open-label, Phase III Trial of Gefitinib Versus Combination of Vinorelbine Plus Platinum as Adjuvant Treatment in Pathological Stage II-IIIA(N1-N2) Non-small Cell Lung Cancer With Epidermal Growth Factor Receptor Activating Mutation

Resource links provided by NLM:


Further study details as provided by Guangdong Association of Clinical Trials:

Primary Outcome Measures:
  • Disease free survival [ Time Frame: Pts after surgery will receive long-term follow-up including chest CT scan, abdominal ultrasound every 3 months, brain MRI every 6 months, bone scan every 12 months for up to 3 years. The survival after 3 years will be followed up with telephone. ] [ Designated as safety issue: No ]
    To evaluate the disease free survival of gefitinib versus combination of vinorelbine plus platinum as adjuvant treatment for pathological stage II-IIIA(N1-N2) NSCLC with EGFR mutation.Disease free survival (DFS)- defined as the time from randomization to the first documented disease progression or death, whichever occurs first.


Secondary Outcome Measures:
  • Overall survival [ Time Frame: Pts after surgery will receive long-term follow-up including chest CT scan, abdominal ultrasound every 3 months, brain MRI every 6 months, bone scan every 12 months for up to 3 years. The survival after 3 years will be followed up with telephone. ] [ Designated as safety issue: No ]
    To evaluate the overall survival of gefitinib versus combination of vinorelbine plus platinum as adjuvant treatment for stage II-IIIA(N1-N2) NSCLC with EGFR mutation.

  • 3 yeas DFS rate, 5 years DFS rate, 5 years OS rate [ Time Frame: Pts after surgery will receive long-term follow-up including chest CT scan, abdominal ultrasound every 3 months, brain MRI every 6 months, bone scan every 12 months for up to 3 years. The survival after 3 years will be followed up with telephone. ] [ Designated as safety issue: No ]
    To compare the randomized treatment arms in terms of 3 yeas DFS rate, 5 years DFS rate, 5 years OS rate.

  • Number of Participants with Adverse Events [ Time Frame: In the period of Gefitinib 250 mg/day oral daily for 24 months.Vinorelbine 25 mg/m2 intravenous infusion on day 1 and day 8, Cisplatin 75 mg/m2 on day 1 for 4 cycles. ] [ Designated as safety issue: Yes ]
    The safety and tolerability profile of gefitinib at a 250 mg daily dose relative to that of Chemotherapy.

  • Quality of life [ Time Frame: In the period of Gefitinib 250 mg/day oral daily for 24 months.Vinorelbine 25 mg/m2 intravenous infusion on day 1 and day 8, Cisplatin 75 mg/m2 on day 1 for 4 cycles. ] [ Designated as safety issue: No ]
    Quality of life as measured by the total score and Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy - Lung Cancer (FACT-L) questionnaire.


Estimated Enrollment: 220
Study Start Date: July 2011
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gefitinib arm
Gefitinib 250 mg/day oral daily for 24 months or disease progression or unacceptable toxicity
Drug: Gefitinib
Gefitinib 250 mg/day oral daily for 24 months or disease progression or unacceptable toxicity
Other Name: Iressa
Active Comparator: Chemo arm
Vinorelbine 25 mg/m2 intravenous infusion on day 1 and day 8, Cisplatin 75 mg/m2 on day 1 for 4 cycles or disease progression or unacceptable toxicity.
Drug: Vinorelbine/Cisplatin
Vinorelbine 25 mg/m2 intravenous infusion on day 1 and day 8, Cisplatin 75 mg/m2 on day 1 for 4 cycles or disease progression or unacceptable toxicity.

Detailed Description:

Adjuvant cisplatin-based chemotherapy is recommended for routine use in patients with stages IIA, IIB, and IIIA non-small cell lung cancer (NSCLC) after complete resection. Cisplatin and vinorelbine combination is the standard of care in adjuvant setting. The BR. 19 trial reported adjuvant gefitinib after complete resection of early stage NSCLC(stage IB 49%, II 38%, III 13%) did not confer disease free survival(DFS) or overall survival(OS) advantage in overall population. While the median gefitinib treatment time is only 4.8 months. There are only 76 patients with EGFR mutations included in this analysis. The study closed prematurely in 2005.

Activating somatic mutations of the tyrosine kinase domain of epidermal growth factor receptor (EGFR) have been characterized in a subset of patients with advanced NSCLC.The EGFR mutation rate was 30% in Chinese NSCLC. Patients harboring these mutations in their tumors show excellent response to EGFR tyrosine kinase inhibitors (EGFR-TKIs). This randomized phase III trial is studying gefitinib to see how well it works compared to cisplatin-based chemotherapy in treating patients who have undergone surgery for stage II-IIIA(N1-N2) NSCLC with EGFR activating mutation in Asian population.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent provided.
  • Males or females aged ≥18 years, < 75 years.
  • Able to comply with the required protocol and follow-up procedures, and able to receive oral medications.
  • Target population is completely resected pathological stage II-IIIA(N1-N2) NSCLC with EGFR exon 19 deletions and exon 21 L858R activating mutation.
  • Patient who can start the investigational therapy within 3-6 weeks after the complete resection
  • ECOG performance status 0-1.
  • Life expectancy ≥12 weeks.
  • Adequate hematological function: Absolute neutrophil count (ANC) ≥2.0 x 109/L, and Platelet count ≥100 x 109/L, and Hemoglobin ≥9 g/dL (may be transfused to maintain or exceed this level).
  • Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN), Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN in subjects without liver metastases; ≤ 5 x ULN in subjects with liver metastases.
  • Adequate renal function: Serum creatinine ≤ 1.25 x ULN, or ≥ 60 ml/min.
  • Female subjects should not be pregnant or breast-feeding.

Exclusion Criteria:

  • Known severe hypersensitivity to gefitinib or any of the excipients of this product.
  • Known severe hypersensitivity to pre-medications required for treatment with cisplatin / vinorelbine doublet chemotherapy.
  • Inability to comply with protocol or study procedures.
  • A serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study.
  • A serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease.
  • Interstitial pneumonia.
  • Patients with prior exposure to agents directed at the HER axis (e.g. erlotinib, gefitinib, cetuximab, trastuzumab).
  • Patients with prior chemotherapy or therapy with systemic anti-tumour therapy (e.g. monoclonal antibody therapy).
  • Patients with prior radiotherapy
  • History of another malignancy in the last 5 years with the exception of the following:Other malignancies cured by surgery alone and having a continuous disease-free interval of 5 years are permitted. Cured basal cell carcinoma of the skin and cured in situ carcinoma of the uterine cervix are permitted.
  • Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease).
  • Eye inflammation or eye infection not fully treated or conditions predisposing the subject to this.
  • Evidence of any other disease, neurological or metabolic dysfunction, physical examination or laboratory finding giving reasonable suspicion of a disease or condition that contraindicated the use of an investigational drug or puts the subject at high risk for treatment-related complications.
  • Patient who has active serious infection (e.g. pyrexia of or 38.0℃ over)
  • Patients who harbouring exon 20 T790M mutation.
  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: NCT01405079

Contacts
Contact: Yi-Long WU, MD +8620,83877855 syylwu@live.cn
Contact: Wen-Zhao ZHONG, MD 008618688389223 13609777314@163.com

Locations
China
Guangdong General Hospital Recruiting
Guangzhou, China
Contact: Xue-Ning YANG, MD       yangxuening@gmail.com   
Contact: Wen-zhao ZHONG, MD       13609777314@163.com   
Sponsors and Collaborators
Guangdong Association of Clinical Trials
Guangdong General Hospital
First Affiliated Hospital, Sun Yat-Sen University
Sun Yat-sen University
Jilin Provincial Tumor Hospital
Liaoning Tumor Hospital & Institute
China Medical University, China
Chinese PLA General Hospital
Peking Union Medical College Hospital
Peking University People's Hospital
Beijing Chest Hospital
The 309 Hospital of People's Liberation Army
Beijing Cancer Hospital
Peking University First Hospital
Tianjin Medical University Cancer Institute and Hospital
Qingdao University
Jiangsu Cancer Institute & Hospital
The First Affiliated Hospital of Soochow University
Fudan University
Shanghai Pulmonary Hospital, Shanghai, China
Zhejiang Cancer Hospital
Zhejiang University
Wuhan Union Hospital, China
Tongji Hospital
West China Hospital
Tang-Du Hospital
Investigators
Principal Investigator: Yi-Long WU, MD Guangdong General Hospital
Study Chair: Xue-Ning YANG, MD Guangdong General Hospital
Study Director: Wen-Zhao ZHONG, MD Guangdong General Hospital
  More Information

Publications:
Responsible Party: Yi-Long Wu, Dr, Guangdong Association of Clinical Trials
ClinicalTrials.gov Identifier: NCT01405079     History of Changes
Other Study ID Numbers: C-TONG 1104, C-TONG 1104
Study First Received: July 26, 2011
Last Updated: September 5, 2013
Health Authority: China: Food and Drug Administration

Keywords provided by Guangdong Association of Clinical Trials:
Lung cancer
II-IIIA(N1-N2)
Adjuvant treatment
EGFR mutations
Tyrosine kinase inhibitor

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
Vinorelbine
Gefitinib
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 01, 2014