First-line Gefitinib Versus Chemotherapy for Lung Adenocarcinoma in Never Smoker

• ClinicalTrials.gov Identifier: NCT00455936
• Recruitment Status: Completed
• First Posted: April 4, 2007
• Last Update Posted: October 25, 2010
• Sponsor: National Cancer Center, Korea
• Collaborator: AstraZeneca
• Information provided by: National Cancer Center, Korea

Tracking Information

• First Submitted Date: April 3, 2007
• First Posted Date: April 4, 2007
• Last Update Posted Date: October 25, 2010
• Study Start Date: October 2005
• Actual Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 22, 2010): overall survival [ Time Frame: every 12 weeks ]
• Original Primary Outcome Measures (submitted: April 3, 2007): To examine whether gefitinib monotherapy would improve overall survival of never-smokers with adenocarcinoma of lung as compared with standard chemotherapy

Current Secondary Outcome Measures (submitted: October 22, 2010)

• To compare Progression-Free survival [ Time Frame: every 9 weeks ]
• To compare the quality of life [ Time Frame: every 3 weeks ]
• To compare safety profile [ Time Frame: every 9 weeks ]
• To collect the tissue samples for the study of predictors of gefitinib (optional) [ Time Frame: screening period ]
• To compare the objective response rate (CR+PR) [ Time Frame: from the date of randomization to the date of death from any cause the result of each should be recorded separately ]

Original Secondary Outcome Measures (submitted: April 3, 2007)

• To compare the objective response rate (CR+PR)
• To compare disease control rate (SD+PR+CR)
• To compare time to progression
• To compare the quality of life
• To compare safety profile
• To collect the tissue samples for the study of predictors of gefitinib (optional)

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

Descriptive Information

• Brief Title: First-line Gefitinib Versus Chemotherapy for Lung Adenocarcinoma in Never Smoker
• 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

Brief Summary

The investigators 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.

Detailed Description

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)

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lung Cancer

Intervention

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

Study Arms

• Experimental: study arm
  Gefitinib 250mg table/QD, daily every 3 weeks
  Intervention: Drug: Gefitinib
• Active Comparator: control arm
  gemcitabine 1250mg/m2 iv on D1 & D8 every 3 weeks Cisplatin 80mg/m2 iv on D1 every 3 weeks
  Intervention: Procedure: chemotherapy

• Publications *: Lee Y, Kim SH, Han JY, Kim HT, Yun T, Lee JS. Early neutrophil-to-lymphocyte ratio reduction as a surrogate marker of prognosis in never smokers with advanced lung adenocarcinoma receiving gefitinib or standard chemotherapy as first-line therapy. J Cancer Res Clin Oncol. 2012 Dec;138(12):2009-16. doi: 10.1007/s00432-012-1281-4. Epub 2012 Jul 7.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 25, 2008): 315
• Original Enrollment (submitted: April 3, 2007): 314
• Actual Study Completion Date: March 2010
• Actual Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Korea, Republic of

Administrative Information

• NCT Number: NCT00455936
• Other Study ID Numbers: NCCCTS-05-126; D7913L00054 ( Other Grant/Funding Number: AstraZeneca )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Jin Soo Lee, National Cancer Center, Korea
• Original Responsible Party: Not Provided
• Current Study Sponsor: National Cancer Center, Korea
• Original Study Sponsor: Same as current
• Collaborators: AstraZeneca

Investigators

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

• PRS Account: National Cancer Center, Korea
• Verification Date: March 2010