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

Non-Small Cell Lung Cancer Clinical Trial

— IMPRESS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01544179
• Other study ID #: D791LC00001
• Status: Completed
• Phase: Phase 3
• Start date: March 15, 2012
• Est. completion date: November 20, 2019

Study information

• Verified date: September 2020
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 265
• Est. completion date: November 20, 2019
• Est. primary completion date: May 5, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Gefitinib
Investigational Drug
• Placebo
Matching placebo as comparator
• Pemetrexed
Chemotherapy (concomitant therapy)
• Cisplatin
Chemotherapy (concomitant therapy)

Locations

Country	Name	City	State
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changchun
China	Research Site	Chengdu
China	Research Site	Chengdu
China	Research Site	Dalian
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Kunming
China	Research Site	Nanjing
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Shijiazhuang
China	Research Site	Suzhou
China	Research Site	Taiyuan
China	Research Site	Ürümqi
China	Research Site	Wuhan
China	Research Site	Xi'an
France	Research Site	Clermont Ferrand
France	Research Site	Lille
France	Research Site	Lyon
France	Research Site	Paris
France	Research Site	Villejuif
Germany	Research Site	Hamburg
Germany	Research Site	Löwenstein
Germany	Research Site	Würzburg
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	Shatin
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Italy	Research Site	Genova
Italy	Research Site	Parma
Italy	Research Site	Perugia
Italy	Research Site	Pisa
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Rozzano
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Kashiwa
Japan	Research Site	Osakasayama
Japan	Research Site	Sakai-shi
Japan	Research Site	Sunto-gun
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Russian Federation	Research Site	St.Petersburg
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Majadahonda
Spain	Research Site	Málaga
Spain	Research Site	Sevilla
Spain	Research Site	Zaragoza
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

China,  France,  Germany,  Hong Kong,  Hungary,  Italy,  Japan,  Korea, Republic of,  Russian Federation,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.

External Links

•   D791LC00001_CSR_Synopsis
•   D791LC00001REDACTED_PROTOCOL