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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer (NSCLC)	Drug: Gefitinib; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 296 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Study Start Date: September 2008
• Actual Primary Completion Date: January 2011
• Actual Study Completion Date: February 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: gefitinib; Gefitinib (Iressa® 250 mg) 1 tablet daily	Drug: Gefitinib; Dose form: 250 mg/tablet; Route: oral; Frequency: 1 tablet per day; Duration: until to objective PD; Other Name: Iressa
Placebo Comparator: placebo; placebo 1 tablet daily	Drug: Placebo; To match Gefitinib

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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
4. 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.
5. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

China, Beijing

Research Site

Beijing, Beijing, China

China, Fujian

Research Site

Fuzhou, Fujian, China

China, Guangdong

Research Site

Guangzhou, Guangdong, China

China, Guangxi

Research Site

Nanning, Guangxi, China

China, Henan

Research Site

Zhengzhou, Henan, China

China, Hubei

Research Site

Wuhan, Hubei, China

China, Jiangsu

Research Site

Nanjing, Jiangsu, China

China, Jilin

Research Site

Changchun, Jilin, China

China, Liaoning

Research Site

Shengyang, Liaoning, China

China, Shanghai

Research Site

Shanghai, Shanghai, China

China, Shanxi

Research Site

Xi'an, Shanxi, China

China, Sichuan

Research Site

Chengdu, Sichuan, China

China, Tianjin

Research Site

Tianjin, Tianjin, China

China, Zhejiang

Research Site

Hangzhou, Zhejiang, China

Sponsors and Collaborators

AstraZeneca

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00770588
• Obsolete Identifiers: NCT00769639
• Other Study ID Numbers: D7913L00071
• First Posted: October 10, 2008
• Results First Posted: August 20, 2012
• Last Update Posted: February 8, 2016
• Last Verified: August 2012

Keywords provided by AstraZeneca:

non-small cell lung cancer (NSCLC); Gefitinib

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; Gefitinib; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents