Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01544179
First received: February 15, 2012
Last updated: September 19, 2016
Last verified: September 2016
  Purpose
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.

Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: Gefitinib
Drug: Placebo
Drug: Pemetrexed
Drug: Cisplatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Progression-Free Survival (Site Read, Investigator Assessment) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.

  • Median Progression-Free Survival (Site Read, Investigator Assessment) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.

  • Median Overall Survival (OS) at Time of PFS Analysis [ Time Frame: 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. ] [ Designated as safety issue: No ]
  • Objective Response Rate (ORR) (Site Read Data) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.

  • Disease Control Rate (DCR) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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

  • Improvement in Trial Outcome Index [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.

  • Time to Worsening in Trial Outcome Index [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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

  • Improvement in FACT-L Total Score [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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

  • Time to Worsening in FACT-L Total Score [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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

  • Improvement in Lung Cancer Subscale [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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

  • Time to Worsening in Lung Cancer Subscale [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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


Enrollment: 287
Study Start Date: March 2012
Estimated Study Completion Date: December 2016
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Placebo
Matching placebo as comparator
Drug: Pemetrexed
Chemotherapy (concomitant therapy)
Drug: Cisplatin
Chemotherapy (concomitant therapy)

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

Ages Eligible for Study:   18 Years to 130 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01544179

  Show 47 Study Locations
Sponsors and Collaborators
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
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01544179     History of Changes
Other Study ID Numbers: D791LC00001 
Study First Received: February 15, 2012
Results First Received: April 29, 2015
Last Updated: September 19, 2016
Health Authority: China: Food and Drug Administration
Hong Kong: Ethics Committee
Taiwan: Institutional Review Board
Korea: Food and Drug Administration
Japan: Ministry of Health, Labor and Welfare
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Ministry of Health
Italy: Ethics Committee
Spain: Ministry of Health and Consumption
Russia: Ministry of Health of the Russian Federation
Hungary: National Institute of Pharmacy

Keywords provided by AstraZeneca:
Non Small Cell Lung Cancer
Gefitinib
Pemetrexed
Treatment Beyond Progression

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
Cisplatin
Pemetrexed
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on December 09, 2016