Overview

This trial is active, not recruiting.

Condition non small cell lung cancer
Treatment azd9291
Phase phase 2
Target EGFR
Sponsor AstraZeneca
Start date May 2014
End date May 2015
Trial size 472 participants
Trial identifier NCT02094261, D5160C00002

Summary

A Phase II, Open Label, Single-arm Study to Assess the Safety and Efficacy of AZD9291 in Patients with Locally Advanced/Metastatic Non Small Cell Lung Cancer whose Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and whose Tumours are Epidermal Growth Factor Receptor Mutation and T790M Mutation Positive

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Once daily tablet 80 mg
azd9291
Once daily tablet 80 mg

Primary Outcomes

Measure
ORR according to RECIST 1.1
time frame: At baseline and every 6 weeks from time of first dose, participants will be followed by CT/MRI scans for RECIST 1.1 until date of progression, for an average of approximately 11 months

Secondary Outcomes

Measure
PFS according to RECIST 1.1
time frame: At baseline and every 6 weeks from time of first dose, participants will be followed by CT/MRI scans for RECIST 1.1 until date of progression, for an average of approximately 11 months
Plasma concentrations of AZD9291 and active metabolites (AZ5104 and AZ7550) and PK parameters following dosing (Cmax, Css max, tmax, tss max, AUC 0-24, AUCss, Css min, CLss/F, RAC and ratio of metabolite to AZD9291)
time frame: Blood samples will be collected from each participant at pre-specified times after the first dose on Cycle 1 Day 1 (pre-dose, 1, 2, 4, 6, 8 hours), Cycle 2 Day 1 (pre-dose), Cycle 3 Day 1 (pre-dose, 1, 2, 4, 6, 8, 10, 12, and 24 hours)
Patient Reported Outcomes by EORTC QLQ-C30 questionnaire
time frame: Questionnaires completed at baseline, every 6 weeks (relative to first dose), discontinuation and every 6 weeks during the progression and survival follow-up periods for approximately 2 years.
QTc interval by digital ECG
time frame: From baseline to date of progression or treatment discontinuation, whichever comes first, assessed for approximately 11 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 up to approximately 60 months.
DoR according to RECIST 1.1
time frame: At baseline and every 6 weeks from time of first dose, participants will be followed by CT/MRI scans for RECIST 1.1 until date of progression, for an average of approximately 11 months
DCR according to RECIST 1.1
time frame: At baseline and every 6 weeks from time of first dose, participants will be followed by CT/MRI scans for RECIST 1.1 until date of progression, for an average of approximately 11 months
Tumour shrinkage according to RECIST 1.1
time frame: At baseline and every 6 weeks from time of first dose, participants will be followed by CT/MRI scans for RECIST 1.1 until date of progression, for an average of approximately 11 months
Patient Reported Outcomes by EORTC QLQ LC13 questionnaire
time frame: Questionnaires completed at baseline, weekly for the fist 3 weeks, then every 6 weeks (relative to first dose), discontinuation and every 6 weeks during the progression and survival follow-up periods for approximately 2 years.

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion: - Aged at least 18 years. Japan patients aged at least 20 years. - Locally advanced/metastatic NSCLC not amenable to curative surgery or radiotherapy - Radiological documentation of disease progression: following 1st line EGFR TKI treatment but who have not received further treatment OR following prior therapy with an EGFR TKI and a platinum-based doublet chemotherapy. Patients who received prior EGFR TKI and platinum-based doublet chemotherapy may have also received additional lines of treatment. All patients must have documented radiological progression on the last treatment administered prior to enrolling in the study. - Disease progression following 1st line EGFR TKI treatment or following prior EGFR TKI and platinum-containing doublet chemotherapy. - Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q). Patients must have central confirmation of tumour T790M mutation positive status from a biopsy sample taken after confirmation of disease progression on the most recent treatment regimen. - World Health Organisation (WHO) performance status 0-1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks. - At least one lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline as ≥ 10mm in the longest diameter (except lymph nodes which must have short axis ≥ 15mm) with computerised tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements. - Females of child-bearing potential using contraception; negative pregnancy test. Exclusion: - Treatment with an EGFR-TKI within 8 days of study entry; any cytotoxic chemotherapy, investigational agents or other anticancer drugs within 14 days of study entry; previous treatment with AZD9291 (or 3rd generation TKIs); major surgery within 4 weeks; radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks; current treatment with potent inhibitors of CYP2C8 and potent inhibitors/inducers of CYP3A4. - Unresolved toxicities from prior therapy. - Unstable spinal cord compression/brain metastases. - Severe/uncontrolled systemic diseases, including uncontrolled hypertension, bleeding diatheses or infection. - Refractory nausea/vomiting, chronic gastrointestinal diseases or bowel resection. - Cardiac disease. - Past history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease. - Inadequate bone marrow reserve or organ function.

Additional Information

Official title Phase II, Open Label, Single-arm Study to Assess Safety and Efficacy of AZD9291 in Patients With Locally Advanced/Metastatic NSCLC Whose Disease Has Progressed With Previous EGFR TKI and Whose Tumours Are EGFR and T790M Mutation Positive
Principal investigator Glenwood Goss, MD
Description This is a phase II, open label, single arm study assessing the safety and efficacy of AZD9291 (80 mg, orally, once daily) in patients with a confirmed diagnosis of Epidermal Growth Factor Receptor mutation positive and T790M mutation positive NSCLC,who have progressed following prior therapy with an approved Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) agent. Patients must agree to provide a biopsy for central confirmation of T790M mutation status following confirmed disease progression on the most recent treatment regimen. The primary objective of the study is to assess the efficacy of AZD9291 by assessment of Objective Response Rate according to RECIST 1.1 by an Independent Central Review.
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by AstraZeneca.
Location data was received from the National Cancer Institute and was last updated in July 2016.