Official Title: “A Randomized Phase III Study of Gefitinib (IRESSATM) Versus Standard Chemotherapy (Gemcitabine Plus Cisplatin) as First-Line Treatment for in Never Smokers Advance or Metastatic Adenocarcinoma of Lung”

we will conduct the randomized trial to determine the role of Gefitinib monotherapy as first-line setting in adenocarcinoma patients with no history of smoking, as compared with the standard combination chemotherapy.

This is a randomized, open label, parallel group, phase III study in never-smokers with advanced or metastatic adenocarcinoma of lung.

After stratification by gender, performance status, and disease stage, patients will be randomized to one of the two treatment arms to receive either gefitinib or standard chemotherapy until clinical or objective disease progression, unacceptable toxicity or patient's refusal, whichever is sooner. The chemotherapy will be administered for no more than nine cycles.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: November 2009

Gefitinib (Iressa TM) Arm - Gefitinib administration 250mg tablet once daily every 3 weeks

standard chemotherapy arm - gemcitabine (1,250mg/m2 for 30 minutes on day 1 and 8 of a 3 week cycle) plus cisplatin (80mg/m2 on day 1 of a 3 week cycle)

Intervention(s) in this Clinical Trial

• Drug: Gefitinib
  • gefitinib 250mg tablet/ QD daily until Progression
• Procedure: chemotherapy
  • gemcitabine(1250mg/m2 iv on D1 & 8) plus Cisplatin (80mg/m2 iv on D1) every 3 weeks, maximum 9 cycles

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • Gefitinib 250mg table/QD, daily every 3 weeks
• Active Comparator: B
  • gemcitabine 1250mg/m2 iv on D1 & D8 every 3 weeks Cisplatin 80mg/m2 iv on D1 every 3 weeks

Primary Measures

• To examine whether gefitinib monotherapy would improve overall survival of never-smokers with adenocarcinoma of lung as compared with standard chemotherapy
  • Time Frame: from the date of randomisation to the date of death from any cause
    Safety Issue?: No

Secondary Measures

• To compare the objective response rate (CR+PR)
  • Time Frame: from the date of randomisation to the date of death from any causehe result of each should be recorded separately
    Safety Issue?: No
• To compare disease control rate (SD+PR+CR)
  • Time Frame: from the date of randomisation to the date of death from any causehe result of each should be recorded separately
    Safety Issue?: No
• To compare Progression-Free survival
  • Time Frame: from the date of randomisation to the first date of progression of disease or of death from any cause
    Safety Issue?: No
• To compare the quality of life
  • Time Frame: D1 of each cycle during treatment period
    Safety Issue?: No
• To compare safety profile
  • Time Frame: treatment peirod and up to and including the 30 day follow-up period
    Safety Issue?: Yes
• To collect the tissue samples for the study of predictors of gefitinib (optional)
  • Time Frame: before treatment
    Safety Issue?: No

Inclusion Criteria:

• 1. Histologically or cytologically confirmed diagnosis of adenocarcinoma of lung with or without BAC features; however, adenocarcinoma combined with other histology, such as small cell carcinoma or squamous carcinoma, is not allowed.
• 2. Stage IIIB with malignant pleural effusion/pleural seeding or stage IV patients
• 3. Age 18-75
• 4. Never-smoking defined as not more than 100 cigarettes during the lifetime
• 5. ECOG performance status of 0-2
• 6. No prior invasive malignancies 5 years prior to study entry except adequately treated cutaneous basal cell carcinoma or uterine cervix in situ cancer
• 7. Serum creatinine ≤ 1.5 mg/dL, serum bilirubin ≤ 1.2 mg/dL (1 x UNL) and SGOT/SGPT ≤ 100 IU/L (2.5 x UNL)
• 8. Serum Hgb ≥ 10 gm/dl, platelet count ≥ 100,000/ul, total WBC count >= 4,000/uL, absolute neutrophil count ≥ 1,500/ul
• 9. Patients must sign an informed consent indicating that they are aware of the investigational nature of the study in keeping with the policy of the hospital. The only approved consent form is attached to this protocol
• 10. The presence of CNS metastases is not considered as an exclusion criterion, provided that there is good control of the symptoms with corticosteroids

Exclusion Criteria:

• 1. Pregnancy or breast-feeding (women of child-bearing potential). Women of childbearing potential must practice acceptable methods of birth control to prevent pregnancy.
• 2. Major surgery other than biopsy within the past two week.
• 3. Known severe hypersensitivity to Gefitinib or any of the excipients of this product
• 4. Any evidence of clinically active interstitial lung disease (patients with chronic, stable, radiographic changes who are asymptomatic need not be excluded)
• 5. As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)
• 6. Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the study
• 7. Concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or St John's
• Wort
• 8. Treatment with a non-approved or investigational drug within 30 days before Day 1 of study treatment.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Cancer Center, Korea

Overall Clinical Trial Officials and Contacts

Jin Soo Lee, M.D. Study Chair National Cancer Center, Korea  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00455936

Study ID Number: NCCCTS-05-126

ClinicalTrials.gov Identifier: NCT00455936

Health Authority: South Korea: Korea Food and Drug Administration (KFDA)