Overview

This trial is active, not recruiting.

Condition locally advanced or metastatic egfr sensitising mutation positive non small cell lung cancer
Treatments azd9291 80 mg/40 mg + placebo, placebo erlotinib 150/100mg, placebo gefitinib 250 mg, erlotinib 150/100 mg, gefitinib 250 mg, placebo azd9291 80 mg/ 40 mg
Phase phase 3
Target EGFR
Sponsor AstraZeneca
Collaborator Parexel
Start date December 2014
End date August 2017
Trial size 650 participants
Trial identifier NCT02296125, 2014-002694-11, D5160C00007, U1111-1160-2242

Summary

To assess the efficacy and safety of AZD9291 versus a standard of care epidermal growth factor receptor tyrosine kinase inhibitor in patients with locally advanced or Metastatic Non Small Cell Lung Cancer

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
AZD9291 (80 mg or 40 mg orally, once daily) plus placebo Erlotinib (150 mg or 100 mg orally, once daily) or placebo Gefitinib (250 mg orally, once daily), in accordance with the randomisation schedule.
azd9291 80 mg/40 mg + placebo
The initial dose of AZD9291 80 mg once daily can be reduced to 40 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
placebo erlotinib 150/100mg Placebo Tarceva 150/100 mg
The initial dose of Placebo Erlotinib 150 mg once daily can be reduced to Placebo 100 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
placebo gefitinib 250 mg Placebo Iressa 250 mg
The initial dose of Placebo Gefitinib 250 mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
(Active Comparator)
Erlotinib (150 mg or 100 mg orally, once daily) or placebo Gefitinib (250 mg orally, once daily) plus placebo AZD9291 (80 mg or 40 mg orally, once daily), in accordance with the randomisation schedule. Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label AZD9291 (crossover to active AZD9291).
erlotinib 150/100 mg Tarceva 150/100 mg
The initial dose of Erlotinib 150mg once daily can be reduced to 10 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria. Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label AZD9291 (crossover to active AZD9291).
gefitinib 250 mg Iressa 250mg
The initial dose of Gefitinib 250mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria. Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label AZD9291 (crossover to active AZD9291).
placebo azd9291 80 mg/ 40 mg
The initial dose of Placebo AZD9291 80 mg once daily can be reduced to Placebo AZD9291 40 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.

Primary Outcomes

Measure
Progression Free Survival (PFS)
time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression (approximately 11.5 months)

Secondary Outcomes

Measure
Objective Response Rate (ORR)
time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression (approximately 11.5 months)
Progression Free Survival (PFS) in patients with positive (or negative) T790M mutation
time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression (approximately 11.5 months)
Overall survival (OS)
time frame: From first dose to end of study or date of death from any cause, whichever comes first, assessed every 6 weeks (approximately 29 months)
Patient Reported Outcome by Therapy Satisfaction (CTSQ-16 Questionnaire)
time frame: Questionnaire completed in cycle 2 and 3, prior to Week 6 scan (approximately 2 months)
Plasma concentrations of AZD9291 and metabolites AZ5104 and AZ7550; and ratio of metabolite to AZD9291
time frame: Blood samples will be collected from each participant at pre-dose, 0.5 to 2 hours, and 3 to 5 hours post-dose on Day 1 Cycle 1, and every other cycle thereafter up to and including Cycle 13 (approximately 9 months)
Patients reported disease-related symptoms and HRQoL by EORTC QLQ-C30
time frame: Questionnaires completed at baseline and every 6 weeks until the time of second progression (approximately 20 months)
Duration of Response (DoR)
time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression (approximately 11.5 months)
Disease Control Rate (DCR)
time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression (approximately 11.5 months)
Depth of response
time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression (approximately 11.5 months)
Patients reported disease-related symptoms and HRQoL by EORTC QLQ-LC13
time frame: Questionnaires completed at baseline, weekly and then every 3 weeks until the time of second progression (approximately 20 months)

Eligibility Criteria

Male or female participants from 18 years up to 130 years old.

Inclusion Criteria: 1. Male or female, aged at least 18 years. 2. Pathologically confirmed adenocarcinoma of the lung. 3. Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy. 4. The tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R). 5. Mandatory provision of an unstained, archived tumour tissue sample in a quantity sufficient to allow for central analysis of EGFR mutation status. 6. Patients must be treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with gefitinib or erlotinib as selected by the participating centre. Prior adjuvant and neo-adjuvant therapy is permitted(chemotherapy, radiotherapy, investigational agents). Exclusion Criteria: 1. Treatment with any of the following: - Prior treatment with any systemic anti-cancer therapy for locally advanced/metastatic NSCLC. - Prior treatment with an EGFR-TKI. - Major surgery within 4 weeks of the first dose of study drug. - Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug. - Patients currently receiving medications or herbal supplements known to be potent inducers of cytochrome P450 (CYP) 3A4. - Alternative anti-cancer treatment - Treatment with an investigational drug within five half-lives of the compound or any of its related material. 2. Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of study drug. 3. Spinal cord compression, symptomatic and unstable brain metastases, except for those patients who have completed definitive therapy, are not on steroids, have a stable neurologic status for at least 2 weeks after completion of the definitive therapy and steroids. 4. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). 5. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9291. 6. Any of the following cardiac criteria: - Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTcF value. - Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG. - Any factors that increase the risk of QTc prolongation or risk of arrhythmic events or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval. 7. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.

Additional Information

Official title A Phase III, Double-blind, Randomised Study to Assess the Safety and Efficacy of AZD9291 Versus a Standard of Care Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor as First Line Treatment in Patients With Epidermal Growth Factor Receptor Mutation Positive, Locally Advanced or Metastatic Non Small Cell Lung Cancer.
Description This is a Phase III, double-blind, randomised study assessing the efficacy and safety of AZD9291 (80 mg orally, once daily) versus a standard of care (SoC) Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) (either gefitinib [250 mg orally, once daily] or erlotinib [150 mg orally, once daily]) in patients with locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) that is known to be EGFR sensitising mutation (EGFRm) positive, treatment-naïve and eligible for first-line treatment with an EGFR-TKI.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by AstraZeneca.