Clinical trial NCT01544179: A Study of IRESSA Treatment Beyond Progression in Addition to Chemotherapy Versus Chemotherapy Alone
Official title: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Keywords: Non Small Cell Lung Cancer
Gefitinib
Pemetrexed
Treatment Beyond Progression
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2012-03-05
Enrollment: 265
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-Free Survival (Site Read, Investigator Assessment)
timeFrame: 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
measure: Median Progression-Free Survival (Site Read, Investigator Assessment)
timeFrame: 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 outcomes:
measure: Overall Survival (OS)
timeFrame: 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.
measure: Median Overall Survival (OS) at Time of PFS Analysis
timeFrame: 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.
measure: Objective Response Rate (ORR) (Site Read Data)
timeFrame: 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.
measure: Disease Control Rate (DCR)
timeFrame: 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.
measure: Improvement in Trial Outcome Index
timeFrame: 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.
measure: Time to Worsening in Trial Outcome Index
timeFrame: 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.
measure: Improvement in FACT-L Total Score
timeFrame: 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.
measure: Time to Worsening in FACT-L Total Score
timeFrame: 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.
measure: Improvement in Lung Cancer Subscale
timeFrame: 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.
measure: Time to Worsening in Lung Cancer Subscale
timeFrame: 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.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Dalian
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Kunming
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Shijiazhuang
country: China
facility: Research Site
city: Suzhou
country: China
facility: Research Site
city: Taiyuan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Xi'an
country: China
facility: Research Site
city: Ürümqi
country: China
facility: Research Site
city: Clermont Ferrand
country: France
facility: Research Site
city: Lille
country: France
facility: Research Site
city: Lyon
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Villejuif
country: France
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Löwenstein
country: Germany
facility: Research Site
city: Würzburg
country: Germany
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Shatin
country: Hong Kong
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Parma
country: Italy
facility: Research Site
city: Perugia
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Rozzano
country: Italy
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Osakasayama
country: Japan
facility: Research Site
city: Sakai-shi
country: Japan
facility: Research Site
city: Sunto-gun
country: Japan
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: St.Petersburg
country: Russian Federation
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Majadahonda
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
Study officials:
affiliation: AstraZeneca Global R&D, Alderley park, Cheshire, SK10 4TG, UK
name: Yuri Rukazenkov, MD PhD, GCL Oncology
role: STUDY_DIRECTOR
affiliation: 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
name: Tony Mok, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute Gustave Roussy, France
name: Jean-Charles Soria, MD, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Zhangjiang Hi-tech Park, 3F, Room 3102, 199 Liangjing Road, Pudong Shanghai, postal code:201203
name: Haiyi Jiang, M.D. MSc
role: STUDY_DIRECTOR
References:
citation: 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.