Assess the Efficacy, Safety and Tolerability of Gefitinib (Iressa® 250mg) as Maintenance Therapy in Locally Advanced or Metastatic (Stage IIIB/IV) Non Small Cell Lung Cancer (NSCLC) (INFORM)

• ClinicalTrials.gov Identifier: NCT00770588
• Recruitment Status: Completed
• First Posted: October 10, 2008
• Results First Posted: August 20, 2012
• Last Update Posted: February 8, 2016
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: October 9, 2008
• First Posted Date: October 10, 2008
• Results First Submitted Date: January 17, 2012
• Results First Posted Date: August 20, 2012
• Last Update Posted Date: February 8, 2016
• Study Start Date: September 2008
• Actual Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 20, 2012)

Progression Free Survival (PFS) [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first.The primary analysis of PFS will be performed when at least 265 events have occurred, which is expected to occur approximately. ]

PFS will be calculated from the tumour measurements collected at each tumour assessment per the RECIST criteria and/or the date of patient death. Progression is defined, using RECIST, as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline.

• Original Primary Outcome Measures (submitted: October 9, 2008): PFS: progression free survival will be calculated by AstraZeneca from the tumour measurements per the RECIST criteria and/or the date of patient death. [ Time Frame: The PFS will be assessed from the time of randomisation to the date of any of the following event, whichever occur first: Objective progression is observed and documented and Death from any cause. ]

Current Secondary Outcome Measures (submitted: August 20, 2012)

• Overall Survival (OS) [ Time Frame: The OS will be assessed from the time of randomization to death from any cause.For patients not known to have died or who have withdrawn from the study for whatever reason,OS will be censored at the last date at which patients were known to be alive. ]
  The OS will be assessed from the time of randomisation to death from any cause. For patients not known to have died(which may include those who have been lost to follow up or who have withdrawn from the study for whatever reason), OS will be censored for the analysis at the last date at which the patients were known to be alive.
• Objective Tumour Response (ORR) [ Time Frame: TTumour assessment using RECIST will be performed at baseline then every 42 days (6 weeks) ± 7 days (1 week) from randomisation until objective progression or death from any cause. ]
  The objective tumour response will be calculated as the number of patients with CR or PR per RECIST Criteria. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
• Disease Control Rate (DCR) [ Time Frame: Tumour assessment using RECIST will be performed at baseline then every 42 days (6 weeks) ± 7 days (1 week) from randomisation until objective progression or death from any cause. ]
  DCR will be calculated as the number of patients with CR, PR or sustained SD≥6 weeks per RECIST Criteria. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase
• Symptom Improvement [ Time Frame: at randomization, every 6 weeks until disease progression, and at discontinuation. ]
  Symptom improvement will be assessed from the 7-question Lung Cancer Subscale domain score derived from the FACT-L questionnaire. It is defined as an increase of two or more points on the LCS from randomization, maintained for 21 or more days. It will be calculated as the number of patients analysed with improvement.
• Adverse Event [ Time Frame: AEs and SAEs must be collected from the time that the main study informed consent is obtained to 28 days after discontinuation of study drug. Any ongoing AE or SAE at discontinuation of study treatment and during 28 day follow-up period must be monitored ]
  Appropriate description of AEs and laboratory data/vital signs will be produced. Number of patients who had at least one adverse events will be calculated.

Original Secondary Outcome Measures (submitted: October 9, 2008)

• Overall Survival (OS) [ Time Frame: The OS will be assessed from the time of randomisation to death from any cause. For patients not known to have died, OS will be censored for the analysis at the last date at which the patients were known to be alive. ]
• ORR (Objective tumour response) & DCR (Disease control rate) [ Time Frame: The objective tumour response rate will be calculated as the percentage of patients with CR or PR. The disease control rate will be calculated as the percentage of patients with CR or PR or sustained SD≥6weeks. ]
• Improvement in LCS (Lung Cancer Subscale) will be assessed from the 7-question LCS domain score in FACT-L (Functional Assessment of Cancer Therapy-Lung) questionnaire. [ Time Frame: Overall improvement in LCS is defined as an improvement from baseline in the LCS domain score of 2 points or more maintained for at least 21 days. The LCS improvement rate will be calculated as the percentage of patients analysed with improvement. ]
• Safety profiles will be assessed in terms of AEs and laboratory data/vital signs that will be collected for all patients. [ Time Frame: Appropriate descriptive of AEs and laboratory data/vital signs will be produced for the 2 treatments. Incidence and reasons for study drug dose modifications (interruptions or reductions) and withdrawals will be summarised by each treatment. ]

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

Descriptive Information

• Brief Title: Assess the Efficacy, Safety and Tolerability of Gefitinib (Iressa® 250mg) as Maintenance Therapy in Locally Advanced or Metastatic (Stage IIIB/IV) Non Small Cell Lung Cancer (NSCLC)
• Official Title: A Placebo-Controlled, Multicentre, Randomised, Parallel Group, Trial to Assess the Efficacy, Safety and Tolerability of Gefitinib (Iressa® 250mg) as Maintenance Therapy in Locally Advanced or Metastatic (StageIIIB/IV) Non Small Cell Lung Cancer (NSCLC) Chinese Patients Who HaveNot Experienced Disease Progression or Unacceptable Toxicity During Front Line Standard Platinum-Based Chemotherapy
• Brief Summary: This is a double blind, multicentre, randomized, placebo-controlled study. The eligible patients will be randomized to receive gefitinib or placebo at 1:1 ratio. This study will recruit 296 male or female, histologically or cytologically diagnosed locally advanced or metastatic NSCLC patients with a World Health Organization (WHO) Performance Status (PS) 0-2. Patients must have completed 4 cycles of platinum based first line doublet chemotherapy without experiencing disease progression or unacceptable toxicity. The chemotherapy shall be given every 3 weeks, which includes cisplatin or carboplatin, combined with any one of the following: gemcitabine, paclitaxel, docetaxel, vinorelbine.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Non-small Cell Lung Cancer (NSCLC)

Intervention

• Drug: Gefitinib
  Dose form: 250 mg/tablet; Route: oral; Frequency: 1 tablet per day; Duration: until to objective PD
  Other Name: Iressa
• Drug: Placebo
  To match Gefitinib

Study Arms

• Experimental: gefitinib
  Gefitinib (Iressa® 250 mg) 1 tablet daily
  Intervention: Drug: Gefitinib
• Placebo Comparator: placebo
  placebo 1 tablet daily
  Intervention: Drug: Placebo

Publications *

• Zhao H, Fan Y, Ma S, Song X, Han B, Cheng Y, Huang C, Yang S, Liu X, Liu Y, Lu S, Wang J, Zhang S, Zhou C, Wang M, Zhang L; INFORM investigators. Final overall survival results from a phase III, randomized, placebo-controlled, parallel-group study of gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-small-cell lung cancer (INFORM; C-TONG 0804). J Thorac Oncol. 2015 Apr;10(4):655-64. doi: 10.1097/JTO.0000000000000445.
• Zhang L, Ma S, Song X, Han B, Cheng Y, Huang C, Yang S, Liu X, Liu Y, Lu S, Wang J, Zhang S, Zhou C, Zhang X, Hayashi N, Wang M; INFORM investigators. Gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-small-cell lung cancer (INFORM; C-TONG 0804): a multicentre, double-blind randomised phase 3 trial. Lancet Oncol. 2012 May;13(5):466-75. doi: 10.1016/S1470-2045(12)70117-1. Epub 2012 Apr 17.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 9, 2008): 296
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: February 2011
• Actual Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed locally advanced or metastatic (stage=IIIB/IV) non-small cell lung cancer (NSCLC) before the front line chemotherapy. Note: sputum cytology alone is not acceptable
• Patients have completed 4 cycles of first line platinum contained doublet chemotherapy without progression or intolerable toxicity.
• Patients with PR or SD on study entry need to have one or more measurable lesions according to RECIST criteria.
• The study treatment should be started at least 3 weeks (21 days) but no more than 6 weeks (42 days) since last dose of chemotherapy, and within 4 weeks (28 days) since last tumour assessment.

Exclusion Criteria:

• Prior exposure to monoclonal antibodies or small molecule inhibitors against EGFR receptors. (e.g. gefitinib, erlotinib, C225)
• Patients with previously diagnosed and treated CNS metastases or spinal cord compression may be considered if they are clinically stable and have been discontinued from steroid therapy for at least 4 weeks prior to first dose of study medication.
• Any evidence of clinically active interstitial lung disease (patients with chronic, stable, radiographic changes who are asymptomatic need not be excluded)
• Known biomarker status of one or more of the following: Tumour EGFR gene copy number, tumour EGFR gene mutation status, tumour EGFR protein expression.

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

Administrative Information

• NCT Number: NCT00770588
• Other Study ID Numbers: D7913L00071
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: AstraZeneca
• Original Responsible Party: Karen Atkin/VP, China R&D, AstraZeneca (China) Pharmaceuticals
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: AstraZeneca
• Verification Date: August 2012