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 Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Non-small Cell Lung Cancer (NSCLC)
• Interventions: Drug: Gefitinib; Drug: Placebo
• Enrollment: 296

Participant Flow

Recruitment Details	A total of 298 patients were screened for the study and 296 subsequently randomized
Pre-assignment Details

Arm/Group Title	Gefitinib	Placebo
Arm/Group Description	Gefitinib (Iressa® 250 mg) 1 tablet daily	placebo 1 tablet daily
Period Title: Overall Study
Started	148	148
Completed	67	53
Not Completed	81	95
Reason Not Completed
Adverse Event	9	2
Death caused by progression of disease	70	91
Lost to Follow-up	1	1
Withdrawal by Subject	1	1

Baseline Characteristics

Arm/Group Title		Gefitinib	Placebo	Total
Arm/Group Description		Gefitinib (Iressa® 250 mg) 1 tablet daily	placebo 1 tablet daily	Total of all reporting groups
Overall Number of Baseline Participants		148	148	296
Baseline Analysis Population Description		[Not Specified]
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	148 participants	148 participants	296 participants
<45 years		22	22	44
45-64 years		107	108	215
65-74 years		18	17	35
>=75 years		1	1	2
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	148 participants	148 participants	296 participants
	Female	65 43.9%	56 37.8%	121 40.9%
	Male	83 56.1%	92 62.2%	175 59.1%
Smoking status; Measure Type: Number; Unit of measure: Participants	Number Analyzed	148 participants	148 participants	296 participants
non-smoker		79	81	160
ex-smoker		57	55	112
current smoker		12	12	24

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	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.
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gefitinib	Placebo
Arm/Group Description:	Gefitinib (Iressa® 250 mg) 1 tablet daily	placebo 1 tablet daily
Overall Number of Participants Analyzed	148	148
Median (95% Confidence Interval); Unit of Measure: month
	4.8; (3.19 to 8.54)	2.6; (1.61 to 2.76)

2. Secondary Outcome

Title	Overall Survival (OS)
Description	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.
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gefitinib	Placebo
Arm/Group Description:	Gefitinib (Iressa® 250 mg) 1 tablet daily	placebo 1 tablet daily
Overall Number of Participants Analyzed	148	148
Median (95% Confidence Interval); Unit of Measure: month
	18.7; (15.6 to 22.2)	16.9; (14.5 to 19.0)

3. Secondary Outcome

Title	Objective Tumour Response (ORR)
Description	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.
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gefitinib	Placebo
Arm/Group Description:	Gefitinib (Iressa® 250 mg) 1 tablet daily	placebo 1 tablet daily
Overall Number of Participants Analyzed	148	148
Measure Type: Number; Unit of Measure: Participants
	35	1

4. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	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
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.

Outcome Measure Data Not Reported

5. Secondary Outcome

Title	Symptom Improvement
Description	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.
Time Frame	at randomization, every 6 weeks until disease progression, and at discontinuation.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gefitinib	Placebo
Arm/Group Description:	Gefitinib (Iressa® 250 mg) 1 tablet daily	placebo 1 tablet daily
Overall Number of Participants Analyzed	148	148
Measure Type: Number; Unit of Measure: Participants
	34	12

6. Secondary Outcome

Title	Adverse Event
Description	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.
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gefitinib	Placebo
Arm/Group Description:	Gefitinib (Iressa® 250 mg) 1 tablet daily	Placebo 1 tablet daily
Overall Number of Participants Analyzed	147	148
Measure Type: Number; Unit of Measure: Participants
	118	79

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Gefitinib	Placebo
Arm/Group Description	Gefitinib (Iressa® 250 mg) 1 tablet daily	placebo 1 tablet daily
All-Cause Mortality
	Gefitinib	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Gefitinib	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	10/147 (6.80%)	5/148 (3.38%)
General disorders
Death † 1	1/147 (0.68%)	0/148 (0.00%)
Sudden Death † 1	1/147 (0.68%)	0/148 (0.00%)
Accidental Death † 1	0/147 (0.00%)	1/148 (0.68%)
Infections and infestations
Lung Infection † 1	2/147 (1.36%)	0/148 (0.00%)
Pneumonia † 1	2/147 (1.36%)	0/148 (0.00%)
Investigations
Alanine Aminotransferase Increased † 1	0/147 (0.00%)	1/148 (0.68%)
Aspartate Aminotransferase Increased † 1	0/147 (0.00%)	1/148 (0.68%)
Nervous system disorders
Paraplegia † 1	1/147 (0.68%)	0/148 (0.00%)
Psychiatric disorders
Completed Suicide † 1	0/147 (0.00%)	1/148 (0.68%)
Respiratory, thoracic and mediastinal disorders
Interstitial Lung Disease † 1	2/147 (1.36%)	0/148 (0.00%)
Haemoptysis † 1	1/147 (0.68%)	0/148 (0.00%)
Pleural Effusion † 1	0/147 (0.00%)	1/148 (0.68%)
Skin and subcutaneous tissue disorders
Subcutaneous Nodule † 1	0/147 (0.00%)	1/148 (0.68%)
Vascular disorders
Arterial Thrombosis Limb † 1	1/147 (0.68%)	0/148 (0.00%)
Circulatory Collapse † 1	1/147 (0.68%)	0/148 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 12.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Gefitinib	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	118	79
Gastrointestinal disorders
diarrhoea † 1	37/147 (25.17%)	13/148 (8.78%)
Investigations
Alanine Aminotransferase Increased † 1	31/147 (21.09%)	12/148 (8.11%)
aspartate aminotransferase increased † 1	21/147 (14.29%)	6/148 (4.05%)
transaminases increased † 1	8/147 (5.44%)	2/148 (1.35%)
serious hepatic dysfunction † 1	43/147 (29.25%)	16/148 (10.81%)
Respiratory, thoracic and mediastinal disorders
cough † 1	9/147 (6.12%)	20/148 (13.51%)
Skin and subcutaneous tissue disorders
rash † 1	73/147 (49.66%)	14/148 (9.46%)
pruritus † 1	10/147 (6.80%)	7/148 (4.73%)
dry skin † 1	9/147 (6.12%)	3/148 (2.03%)
skin exfoliation † 1	9/147 (6.12%)	0/148 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 12.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

PI agrees to collaborate in good faith with AZ regard to contents and formation of any publication and to pay due consideration to the comments, views and opinions offered by AZ. AZ shall have a period of 30 days from receipt of the proposed final manuscript to review and may require submission be delayed in order for AZ to file patent application

Results Point of Contact

• Name/Title: Gerard Lynch
• Organization: AstraZeneca
• Phone: 52564555 ext 86 21
• EMail: aztrial_results_posting@astrazeneca.com

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 Submitted: October 9, 2008
• First Posted: October 10, 2008
• Results First Submitted: January 17, 2012
• Results First Posted: August 20, 2012
• Last Update Posted: February 8, 2016