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

Phase 3

Completed

• Conditions: Non-Small Cell Lung Cancer
• Interventions: Drug: Placebo; Drug: Gefitinib; Drug: Pemetrexed; Drug: Cisplatin

• Registration Number: NCT01544179
• Lead Sponsor: AstraZeneca

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.

Study Timeline

• Study First Submitted: 2012-02-15
• Study First Submitted QC: 2012-03-02
• Study First Posted: 2012-03-05
• Study Start: 2012-03-15
• Primary Completion: 2014-05-05
• Results First Submitted: 2015-04-29
• Results First Submitted QC: 2016-01-19
• Results First Posted: 2016-02-15
• Study Completion: 2019-11-20
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-24
• Last Update Posted: 2020-09-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 265

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Pemetrexed	Placebo and cisplatin plus pemetrexed combination chemotherapy.
Gefitinib	Cisplatin	Gefitinib and cisplatin plus pemetrexed combination chemotherapy
Placebo	Placebo	Placebo and cisplatin plus pemetrexed combination chemotherapy.
Gefitinib	Gefitinib	Gefitinib and cisplatin plus pemetrexed combination chemotherapy
Gefitinib	Pemetrexed	Gefitinib and cisplatin plus pemetrexed combination chemotherapy
Placebo	Cisplatin	Placebo and cisplatin plus pemetrexed combination chemotherapy.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (Site Read, Investigator Assessment)	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	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)	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	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

Name	Time	Method
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.
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.	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
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.	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.
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.	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.
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.	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	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.	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	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.	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	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.	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
Time to Worsening in Lung Cancer Subscale	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.	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
Improvement in Lung Cancer Subscale	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.	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

Trial Locations

Locations (1)

Research Site; 🇨🇳 Taipei, Taiwan