A Study of IRESSA Treatment Beyond Progression in Addition to Chemotherapy Versus Chemotherapy Alone (IMPRESS)

A Phase III Randomised, Double Blind, Placebo Controlled, Parallel, Multicentre Study to Assess the Efficacy and Safety of Continuing IRESSA 250 mg in Addition to Chemotherapy Versus Chemotherapy Alone in Patients Who Have Epidermal Growth Factor Receptor (EGFR) Mutation Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) and Have Progressed on First Line IRESSA

The purpose of this study is to assess the efficacy and safety of gefitinib in patients who have progressed on first line gefitinib, comparing continuing gefitinib in addition to cisplatin plus pemetrexed combination chemotherapy versus cisplatin plus pemetrexed combination chemotherapy alone.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Gefitinib; Drug: Pemetrexed; Drug: Cisplatin; Drug: Placebo

Detailed Description

A Phase III Randomised, Double blind, Placebo controlled, Parallel, Multicentre Study to Assess the Efficacy and Safety of continuing IRESSA 250 mg in addition to Chemotherapy versus Chemotherapy alone in Patients who have Epidermal Growth Factor Receptor (EGFR) Mutation Positive Locally advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) and have progressed on First Line IRESSA.

• Study Type: Interventional
• Enrollment (Actual): 265
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100020
    • Research Site
  • Beijing, China, 100021
    • Research Site
  • Beijing, China, 100071
    • Research Site
  • Beijing, China, 100730
    • Research Site
  • Beijing, China, 100853
    • Research Site
  • Beijing, China, 101149
    • Research Site
  • Changchun, China, 130012
    • Research Site
  • Changchun, China, 130021
    • Research Site
  • Chengdu, China, 610041
    • Research Site
  • Chengdu, China, 610042
    • Research Site
  • Dalian, China, 116011
    • Research Site
  • Guangzhou, China, 510120
    • Research Site
  • Guangzhou, China, 510000
    • Research Site
  • Hangzhou, China, 310003
    • Research Site
  • Kunming, China, 650118
    • Research Site
  • Nanjing, China, 210002
    • Research Site
  • Shanghai, China, 200032
    • Research Site
  • Shanghai, China, 200030
    • Research Site
  • Shenyang, China, 110001
    • Research Site
  • Shijiazhuang, China, 050011
    • Research Site
  • Suzhou, China, 215004
    • Research Site
  • Taiyuan, China, 030000
    • Research Site
  • Wuhan, China, 430022
    • Research Site
  • Xi'an, China, 710061
    • Research Site
  • Ürümqi, China, 830000
    • Research Site
• France
  • Clermont Ferrand, France, 63003
    • Research Site
  • Lille, France, 59037
    • Research Site
  • Lyon, France, 69373
    • Research Site
  • Paris, France, 75020
    • Research Site
  • Villejuif, France, 94805
    • Research Site
• Germany
  • Hamburg, Germany, 21075
    • Research Site
  • Löwenstein, Germany, 74245
    • Research Site
  • Würzburg, Germany, 97067
    • Research Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Research Site
  • Shatin, Hong Kong
    • Research Site
• Hungary
  • Budapest, Hungary, 1121
    • Research Site
  • Budapest, Hungary, 1145
    • Research Site
• Italy
  • Genova, Italy, 16100
    • Research Site
  • Parma, Italy, 43126
    • Research Site
  • Perugia, Italy, 06132
    • Research Site
  • Pisa, Italy, 56124
    • Research Site
  • Roma, Italy, 00128
    • Research Site
  • Roma, Italy, 00144
    • Research Site
  • Rozzano, Italy, 20089
    • Research Site
• Japan
  • Fukuoka-shi, Japan, 811-1395
    • Research Site
  • Kashiwa, Japan, 277-8577
    • Research Site
  • Osakasayama, Japan, 589-8511
    • Research Site
  • Sakai-shi, Japan, 591-8555
    • Research Site
  • Sunto-gun, Japan, 411-8777
    • Research Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Research Site
  • Seoul, Korea, Republic of, 135-710
    • Research Site
• Russian Federation
  • St.Petersburg, Russian Federation, 197022
    • Research Site
• Spain
  • Barcelona, Spain, 08003
    • Research Site
  • Barcelona, Spain, 08025
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Majadahonda, Spain, 28222
    • Research Site
  • Málaga, Spain, 29010
    • Research Site
  • Sevilla, Spain, 41009
    • Research Site
  • Zaragoza, Spain, 50009
    • Research Site
• Taiwan
  • Taichung, Taiwan, 40705
    • Research Site
  • Taipei, Taiwan, 10002
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patients aged 18 years or older (For Japan only- male or female patients aged 20 years or older)
• Cytological or histological confirmation of NSCLC other than predominantly squamous cell histology with an activating EGFR TK mutation as determined locally
• Patients with documented 'acquired resistance' on first line gefitinib
• Patients suitable to start cisplatin based pemetrexed combination chemotherapy.
• Provision of informed consent prior to any study specific procedures.

Exclusion Criteria:

• Prior chemotherapy or other systemic anti-cancer treatment (excluding gefitinib). Palliative bone radiotherapy must be completed at least 2 weeks before start of study treatment with no persistent radiation toxicity).
• Past medical history of interstitial lung disease, drug-induced interstitial disease, radiation pneumonitis which required steroid treatment or any evidence of clinically active interstitial lung disease
• Other co-existing malignancies or malignancies diagnosed within the last 5 years, with the exception of basal cell carcinoma or cervical cancer in situ or completely resected intramucosal gastric cancer
• Any evidence of severe of uncontrolled systemic disease Treatment with an investigational drug within 4 weeks before randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gefitinib; Gefitinib and cisplatin plus pemetrexed combination chemotherapy	Drug: Gefitinib; Investigational Drug; Drug: Pemetrexed; Chemotherapy (concomitant therapy); Drug: Cisplatin; Chemotherapy (concomitant therapy)
Placebo Comparator: Placebo; Placebo and cisplatin plus pemetrexed combination chemotherapy.	Drug: Pemetrexed; Chemotherapy (concomitant therapy); Drug: Cisplatin; Chemotherapy (concomitant therapy); Drug: Placebo; Matching placebo as comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (Site Read, Investigator Assessment)	PFS is the time from randomisation until the date of objective disease progression as defined by Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) or death (by any cause in the absence of progression). Progression is defined using RECIST (v1.1), as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm.	Radiologic evaluations were carried out every 6 weeks from randomization until documented progression, withdrawal of consent, loss to follow up, death or the primary data cut off (DCO) for the analysis, assessed up to 50 weeks
Median Progression-Free Survival (Site Read, Investigator Assessment)	PFS is the time from randomisation until the date of objective disease progression as defined by Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) or death (by any cause in the absence of progression). Progression is defined using RECIST (v1.1), as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm.	Radiologic evaluations were carried out every 6 weeks from randomization until documented progression, withdrawal of consent, loss to follow up, death or the primary data cut off (DCO) for the analysis, assessed up to 50 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is the time from the date of randomisation until death due to any cause. Any subject not known to have died at the time of analysis will be censored based on the last recorded date on which the subject was known to be alive.	Following progression survival data was collected every 8 weeks until documentation of death, withdrawal of consent, loss to follow-up or the final data cut-off, whichever occurs first.
Median Overall Survival (OS) at Time of PFS Analysis		Baseline and then every 6 weeks after randomization until objective disease progression. OS is then assessed 8 weekly following PFS progression up to PFS analysis data cut off.
Objective Response Rate (ORR) (Site Read Data)	ORR rate is defined as the number (%) of subjects with at least one visit response of Complete Response (CR) or Partial Response (PR) , as defined by Response Evaluation Criteria in Solid Tumours (RECIST v1.1) for target lesions and assessed by CT or MRI. CR, Disappearance of all target lesions; PR, ≥30% decrease in the sum of the longest diameter of target lesions. Data obtained up until progression, or last evaluable assessment in the absence of progression, was included in the assessment of ORR.	Radiologic evaluations were carried out every 6 weeks from randomization until documented progression, withdrawal of consent, loss to follow up, death or the primary data cut off (DCO) for the analysis.
Disease Control Rate (DCR)	DCR is the percentage of patients who achieve disease control at 6 weeks following randomisation. DCR is defined as a Best Objective Response (BOR) of Complete Response, Partial Response or Stable Disease, as defined by Response Evaluation Criteria in Solid Tumours (RECIST v1.1) for target lesions and assessed by CT or MRI. CR, Disappearance of all target lesions; PR, ≥30% decrease in the sum of the longest diameter of target lesions; SD, neither sufficient shrinkage to qualify for PR not sufficient increase to qualify for Progressive Disease (PD); PD, ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, and the sum must have shown an absolute increase of ≥5mm	Radiologic evaluations were carried out every 6 weeks from randomization until documented progression, withdrawal of consent, loss to follow up, death or the primary data cut off (DCO) for the analysis.
Improvement in Trial Outcome Index	An improvement is defined as a change from baseline of ≥ +6 (0-84 score range). Measured by the Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L) questionnaire.	At visits 2-8, then every 6 weeks until progression, at progression or treatment discontinuation, and every 8 weeks after progression until PFS analysis data cut off.
Time to Worsening in Trial Outcome Index	A worsening is defined as a change from baseline of ≤ -6 (0-84 score range). Measured by the Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L) questionnaire	At visits 2-8, then every 6 weeks until progression, at progression or treatment discontinuation, and every 8 weeks after progression until PFS analysis data cut off.
Improvement in FACT-L Total Score	An improvement is defined as a change from baseline of ≥ +6 (0-136 score range). Measured by the Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L) questionnaire	At visits 2-8, then every 6 weeks until progression, at progression or treatment discontinuation, and every 8 weeks after progression until PFS analysis data cut off.
Time to Worsening in FACT-L Total Score	A worsening is defined as a change from baseline of ≤ -6 (0-136 score range). Measured by the Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L) questionnaire	At visits 2-8, then every 6 weeks until progression, at progression or treatment discontinuation, and every 8 weeks after progression until PFS analysis data cut off.
Improvement in Lung Cancer Subscale	An improvement is defined as a change from baseline of ≥ +2 (0-28 score range). Measured by the Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L) questionnaire	At visits 2-8, then every 6 weeks until progression, at progression or treatment discontinuation, and every 8 weeks after progression until PFS analysis data cut off.
Time to Worsening in Lung Cancer Subscale	A worsening is defined as a change from baseline of ≤ -2 (0-28 score range). Measured by the Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L) questionnaire	At visits 2-8, then every 6 weeks until progression, at progression or treatment discontinuation, and every 8 weeks after progression until PFS analysis data cut off.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Yuri Rukazenkov, MD PhD, GCL Oncology, AstraZeneca Global R&D, Alderley park, Cheshire, SK10 4TG, UK; Principal Investigator: Tony Mok, M.D., Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong KongDepartment of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong; Principal Investigator: Jean-Charles Soria, MD, PHD, Institute Gustave Roussy, France; Study Director: Haiyi Jiang, M.D. MSc, Zhangjiang Hi-tech Park, 3F, Room 3102, 199 Liangjing Road, Pudong Shanghai, postal code:201203

Publications and helpful links

General Publications

• Soria JC, Wu YL, Nakagawa K, Kim SW, Yang JJ, Ahn MJ, Wang J, Yang JC, Lu Y, Atagi S, Ponce S, Lee DH, Liu Y, Yoh K, Zhou JY, Shi X, Webster A, Jiang H, Mok TS. Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial. Lancet Oncol. 2015 Aug;16(8):990-8. doi: 10.1016/S1470-2045(15)00121-7. Epub 2015 Jul 6.

Helpful Links

• D791LC00001_CSR_Synopsis
• D791LC00001REDACTED_PROTOCOL

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2012
• Primary Completion (Actual): May 5, 2014
• Study Completion (Actual): November 20, 2019

Study Registration Dates

• First Submitted: February 15, 2012
• First Submitted That Met QC Criteria: March 2, 2012
• First Posted (Estimate): March 5, 2012

Study Record Updates

• Last Update Posted (Actual): September 25, 2020
• Last Update Submitted That Met QC Criteria: September 24, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Non Small Cell Lung Cancer; Pemetrexed; Gefitinib; Treatment Beyond Progression
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Folic Acid Antagonists; Gefitinib; Pemetrexed
• Other Study ID Numbers: D791LC00001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No