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

NCT01544179 | Completed Phase 3 Results DMC

• 1 other identifier: D791LC00001
• Study Type: interventional
• Target: 265
• Locations: 11 countries
• Sites: 61

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

Non Small Cell Lung Cancer; Gefitinib; Pemetrexed; Treatment Beyond Progression

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (10)

• Overall Survival (OS)

  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)

  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)

  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

  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.

Study Arms (2)

Gefitinib

EXPERIMENTAL

Gefitinib and cisplatin plus pemetrexed combination chemotherapy

Drug: Gefitinib; Drug: Pemetrexed; Drug: Cisplatin

Placebo

PLACEBO COMPARATOR

Placebo and cisplatin plus pemetrexed combination chemotherapy.

Drug: Placebo; Drug: Pemetrexed; Drug: Cisplatin

Interventions

Gefitinib DRUG

Investigational Drug

Gefitinib

Placebo DRUG

Matching placebo as comparator

Placebo

Pemetrexed DRUG

Chemotherapy (concomitant therapy)

Gefitinib; Placebo

Cisplatin DRUG

Chemotherapy (concomitant therapy)

Gefitinib; Placebo

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (61)

Research Site

Beijing, 100020, China

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Beijing, 100021, China

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Beijing, 100071, China

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Beijing, 100730, China

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Beijing, 100853, China

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Beijing, 101149, China

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Changchun, 130012, China

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Changchun, 130021, China

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Chengdu, 610041, China

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Chengdu, 610042, China

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Dalian, 116011, China

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Guangzhou, 510000, China

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Guangzhou, 510120, China

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Hangzhou, 310003, China

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Kunming, 650118, China

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Nanjing, 210002, China

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Shanghai, 200030, China

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Shanghai, 200032, China

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Shenyang, 110001, China

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Shijiazhuang, 050011, China

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Suzhou, 215004, China

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Taiyuan, 030000, China

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Ürümqi, 830000, China

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Wuhan, 430022, China

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Xi'an, 710061, China

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Clermont-Ferrand, 63003, France

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Lille, 59037, France

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Lyon, 69373, France

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Paris, 75020, France

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Villejuif, 94805, France

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Hamburg, 21075, Germany

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Löwenstein, 74245, Germany

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Würzburg, 97067, Germany

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Hong Kong, Hong Kong

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Shatin, Hong Kong

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Budapest, 1121, Hungary

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Budapest, 1145, Hungary

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Genova, 16100, Italy

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Parma, 43126, Italy

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Perugia, 06132, Italy

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Pisa, 56124, Italy

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Roma, 00128, Italy

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Roma, 00144, Italy

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Rozzano, 20089, Italy

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Fukuoka, 811-1395, Japan

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Kashiwa, 277-8577, Japan

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Sakaishi, 591-8555, Japan

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Sayama, 589-8511, Japan

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Sunto-gun, 411-8777, Japan

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Saint Petersburg, 197022, Russia

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Seoul, 05505, South Korea

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Seoul, 135-710, South Korea

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Barcelona, 08003, Spain

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Barcelona, 08025, Spain

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Madrid, 28041, Spain

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Majadahonda, 28222, Spain

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Málaga, 29010, Spain

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Seville, 41009, Spain

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Zaragoza, 50009, Spain

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Taichung, 40705, Taiwan

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Taipei, 10002, Taiwan

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Related Publications (1)

• 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.

  PMID: 26159065 DERIVED

Related Links

• D791LC00001\_CSR\_Synopsis
• D791LC00001REDACTED\_PROTOCOL

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Gefitinib; Pemetrexed; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Haiyi Jiang/Asia Medical Director
• Organization: AstraZeneca

haiyi.jiang@astrazeneca.com

+86 21 60302408

Study Officials

• Yuri Rukazenkov, MD PhD, GCL Oncology

  AstraZeneca Global R&D, Alderley park, Cheshire, SK10 4TG, UK

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

• Haiyi Jiang, M.D. MSc

  Zhangjiang Hi-tech Park, 3F, Room 3102, 199 Liangjing Road, Pudong Shanghai, postal code:201203

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2012
• First Posted: March 5, 2012
• Study Start: March 15, 2012
• Primary Completion: May 5, 2014
• Study Completion: November 20, 2019
• Last Updated: September 25, 2020
• Results First Posted: February 15, 2016

Record last verified: 2020-09

Locations

CN (25); TW (2); JP (5); FR (5); HK (2); RU (1); DE (3); IT (7); KR (2); ES (7); HU (2)