Overview

This trial is active, not recruiting.

Condition anticancer treatment
Treatments chemotherapy, cross-over to azd9291
Phase phase 3
Target EGFR
Sponsor AstraZeneca
Start date August 2014
End date April 2016
Trial size 1104 participants
Trial identifier NCT02151981, D5160C00003

Summary

A Phase III, Open Label, Randomized Study of AZD9291 versus Platinum-Based Doublet Chemotherapy for Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer whose Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and whose Tumours harbour a T790M mutation within the Epidermal Growth Factor Receptor Gene

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
AZD9291 80 mg, orally, once daily
chemotherapy AZD9291
Randomization to either AZD9291 or platinum-based doublet-chemotherapy on Day 1 of every 21d cycle in a 2:1 (AZD9291:platinum-based doublet-chemotherapy) ratio
cross-over to azd9291
Once subjects on the platinum-based doublet chemotherapy arm are determined to have objective radiological progression according to RECIST 1.1 by the investigator and confirmed by independent central imaging review, they will be given the opportunity to begin treatment with AZD9291 80mg, once daily. These subjects may continue treatment with AZD9291 even after disease progression, as long as they are continuing to show clinical benefit, as judged by the investigator. Subjects who stop platinum-based doublet chemotherapy for reasons other than objective disease progression according to RECIST 1.1 will not be eligible to cross-over to AZD9291.
(Active Comparator)
pemetrexed 500mg/m2 + carboplatin AUC5 or pemetrexed 500mg/m2 + cisplatin 75mg/m2
chemotherapy AZD9291
Randomization to either AZD9291 or platinum-based doublet-chemotherapy on Day 1 of every 21d cycle in a 2:1 (AZD9291:platinum-based doublet-chemotherapy) ratio

Primary Outcomes

Measure
Progression-Free Survival (PFS)
time frame: At baseline and every 6 weeks from randomization until progression (up to approximately 12 months)

Secondary Outcomes

Measure
Objective Response Rate (ORR)
time frame: At baseline and every 6 weeks from randomization until progression (up to approximately 12 months)
Duration of Response (DoR)
time frame: At baseline and every 6 weeks from randomization until progression (up to approximately 12 months)
Disease Control Rate (DCR)
time frame: At baseline and every 6 weeks from randomization until progression (up to approximately 12 months)
Overall Survival (OS)
time frame: From randomization to end of study (Last subject last visit (LSLV)) (up to approximately 24 months)
Tumour shrinkage according to RECIST 1.1
time frame: At baseline and every 6 weeks from randomization until progression (up to approximately 12 months)
Patient Reported Outcomes by EORTC QLQ-C30 questionnaire
time frame: Questionnaires completed at baseline and every 6 weeks from randomization until end of study (up to approximately 24 months)
Patient Reported Outcomes by EORTC QLQ-LC13 questionnaire
time frame: Questionnaires completed at baseline and every 3 weeks from randomization until end of study (up to approximately 24 months)
Patient Reported Outcomes by EQ-5D-5L questionnaire
time frame: Questionnaires completed at baseline and every 6 weeks from randomization until end of study (up to approximately 24 months)

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Subjects with histologically or cytologically documented NSCLC. - Locally advanced or metastatic NSCLC - Radiological documentation of disease progression following 1st line EGFR TKI Treatment without any further treatment - Eligible to receive treatment with the selected doublet-chemotherapy - Central confirmation of T790M+ mutation status - World Health Organization (WHO) performance status 0-1 - At least one lesion, not previously irradiated. Exclusion Criteria: - • Prior neo-adjuvant or adjuvant chemotherapy treatment within 6 months prior of starting 1st EGFR TKI treatment - Treatment with more than one prior line of treatment for advanced NSCLC - Treatment with an approved EGFR-TKI (e.g.,erlotinib, gefitinib, afatinib) within 8 days or approximately 5x half-life of the first dose of study treatment - Any investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment - Previous treatment with AZD9291, or a 3rd generation EGFR TKI For subjects who cross-over to AZD9291: - Once subjects on the platinum-based doublet chemotherapy arm are determined to have objective radiological progression according to RECIST 1.1 by the investigator and confirmed by independent central imaging review. - At least 14 days since last dose of platinum-based doublet chemotherapy

Additional Information

Official title A Phase III, Open Label, Randomized Study of AZD9291 Versus Platinum-Based Doublet Chemotherapy for Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Whose Disease Has Progressed With Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Whose Tumours Harbour a T790M Mutation Within the Epidermal Growth Factor Receptor Gene (AURA3)
Principal investigator Tony Mok, MD
Description This is a phase III, open label, randomized study assessing AZD9291 (80 mg, orally, once daily) versus platinum-based doublet chemotherapy (standard of care) in subjects with confirmed diagnosis of Epidermal Growth Factor Receptor (EGFR) mutation positive NSCLC, who have progressed following prior therapy with an approved Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) agent and whose tumours harbour a T790M mutation within the EGFR Gene. Subjects must be chemotherapy naive and must agree to provide a biopsy for central confirmation of T790 mutation status following confirmed disease progression on their first line EGFR-TKI treatment (e.g. erlotinib, gefitinib or afatinib). Suitable subjects will then be randomized to receive either AZD9291 (80mg orally, once daily) or platinum-based doublet chemotherapy (pemetrexed 500 mg/m2 + carboplatin area under the plasma concentration-time curve AUC 5 or pemetrexed 500 mg/m2 + cisplatin 75 mg/m2) on Day 1 of every 21-day cycle in a 2:1 (AZD9291: platinum-based doublet chemotherapy) ratio. Once subjects on the platinum-based doublet chemotherapy arm are determined to have objective radiological progression according to RECIST 1.1 by the investigator and confirmed by independent central imaging review, they will be given the opportunity to begin treatment with AZD9291 80mg, once daily. These subjects may continue treatment with AZD9291 even after disease progression, as long as they are continuing to show clinical benefit, as judged by the investigator. The primary objective of the study is to assess the efficacy of AZD9291 compared with platinum-based doublet chemotherapy by assessment of Progression Free Survival (PFS), using investigator assessments according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1), as well as asensitivity analysis of Progression Free Survival using Blinded Independent Central Review (BICR).
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by AstraZeneca.