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AZD9291 First Time In Patients Ascending Dose Study (AURA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by AstraZeneca
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01802632
First received: February 25, 2013
Last updated: October 28, 2014
Last verified: October 2014
  Purpose

This study will treat patients with advanced NSCLC who have already received at least one course of specific anti-cancer treatment but the tumour has started to re-grow following that treatment. This is the first time this drug has ever been tested in patients, and so it will help to understand what type of side effects may occur with the drug treatment, it will measure the levels of drug in the body, it will also measure the anti-cancer activity. By using these pieces of information together the best dose of this drug to use in further clinical trials will be selected.


Condition Intervention Phase
Advanced Non Small Cell Lung Cancer
Advanced (Inoperable) Non Small Cell Lung Cancer
Drug: AZD9291
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of AZD9291 in Patients With Advanced Non Small Cell Lung Cancer Who Progressed on Prior Therapy With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Agent

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Safety, tolerability and efficacy (ORR) of AZD9291, assessed by number and severity of adverse events as recorded on the case report form, vital signs, laboratory variables, physical examination, electrocardiogram, ophthalmic examinations and RECIST1.1 [ Time Frame: Adverse events will be collected from baseline until 28 days after the last dose, expected average 6 months ] [ Designated as safety issue: Yes ]
    Physical exam (screening, first dosing day, first day of multiple dosing, Day 1 of every 3-week cycle and treatment discontinuation). ECG and vital signs (screening, Day 1 and 2 of first dosing, Day 1, 8 and 15 of multiple dosing and Day 1 of every 3-week cycle, treatment discontinuation, and if occurrence of any cardiac adverse event). Lab variables (screening, first dosing day, Day 1, 8 and 15 of multiple dosing, Day 1 of every 3-week cycle and treatment discontinuation). Eye exam (at screening and upon occurrence of any visual AE). CT/MRI at screening and every 6 weeks until progression


Secondary Outcome Measures:
  • Plasma concentrations of AZD9291 and 2 active metabolites (AZ5104 and AZ7550) and pharmacokinetic parameters following single dose (Cmax, tmax, AUC, terminal rate constant, clearance, half life, volume of distribution and mean resistance time) [ Time Frame: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1 (pre-dose, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 48, 72, 120 hours post dose) ] [ Designated as safety issue: No ]
  • Plasma concentrations of AZD9291 and 2 active metabolites (AZ5104 and AZ7550) and pharmacokinetic parameters following dosing with AZD9291 (Cmax, tmax, AUC, terminal rate constant, clearance, half life, volume of distribution and mean resistance time) [ Time Frame: A blood sample will be taken on the day of the optional tumour biopsy (pre-dose and at the time of the tumour biopsy on Cycle 1 Day 15) ] [ Designated as safety issue: No ]
  • Plasma concentrations of AZD9291 and 2 active metabolites (AZ5104 and AZ7550) and pharmacokinetic parameters following multiple doses (steady state Cmax, tmax, Cmin AUC, clearance, accumulation ratio and time dependency) [ Time Frame: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8 and 15. Cycle 2- pre-dose, 1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours post dose) ] [ Designated as safety issue: No ]
  • Pharmacodynamic markers to assess correlations with disease activity, effects of study drug and clinical outcomes [ Time Frame: Optional tumour biopsy samples will be collected at screening, Day 15 and treatment discontinuation, expected average 6 months ] [ Designated as safety issue: No ]
  • Pharmacodynamic markers to assess correlations with disease activity, effects of study drug and clinical outcomes [ Time Frame: Plasma samples for extraction and analysis of circulating free tumour DNA (cfDNA) will be taken at screening, day 1 of dosing, 6 weekly (in line with RECIST assessments), discontinuation, 28 days after last dose and disease progression ] [ Designated as safety issue: No ]
  • Evaluation of tumour response, duration of response, tumour shrinkage, progression free survival and overall survival as assessed by RECIST 1.1 [ Time Frame: CT or MRI at screening and every 6 weeks (from first dose of multiple dosing) until disease progression or withdrawal from study, expected average 6 months ] [ Designated as safety issue: No ]
  • Pharmacodynamic markers in EGFRm+ T790M+ tumours at selective endpoints [ Time Frame: Optional tumour biopsy samples collected at screening and Cycle 1 Day 15 (Paired Biopsy) ] [ Designated as safety issue: No ]
  • Patient reported outcomes: EORTC QLQ C-30 and QLQ-LC13 [ Time Frame: Expansion and Extension cohorts only: Questionnaires completed at screening, Cycle 1 Day 1, every 6 weeks relative to first dose, discontinuation and progression ] [ Designated as safety issue: No ]
  • Pharmacogenetics [ Time Frame: Optional blood sample collected during screening, no more than 28 days before first dose of AZD9291 ] [ Designated as safety issue: No ]

Estimated Enrollment: 375
Study Start Date: March 2013
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Daily dose of AZD9291
Daily oral dose of AZD9291
Drug: AZD9291
Starting dose 20 mg, administered once daily. If tolerated subsequent cohorts will test increasing doses of AZD9291, until a maximum tolerated dose or maximum feasible dose is defined

Detailed Description:

A Phase I/II, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of Ascending Doses of AZD9291 in Patients with Advanced Non Small Cell Lung Cancer who have Progressed Following Prior Therapy with an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Agent (AURA)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses
  • Aged at least 18 years. Patients from Japan aged at least 20 years.
  • Histological or cytological confirmation diagnosis of Non Small Cell Lung Cancer (NSCLC).
  • Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI e.g. gefitinib or erlotinib (with the exception of 1st line expansion cohort). In addition other lines of therapy may have been given. All patients must have documented radiological progression on the last treatment administered prior to enrolling in the study.
  • Patients (with the exception of 1st line expansion cohort) must fulfil one of the following:

    • Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) OR
    • Must have experienced clinical benefit from EGFR TKI, according to the Jackman criteria (Jackman et al 2010) followed by systemic objective progression (RECIST or WHO) while on continuous treatment with EGFR TKI.
  • Previous treatment with a single-agent EGFR TKI (e.g. gefitinib or erlotinib).
  • Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing or evidence of non-child bearing potential.
  • Male patients should be willing to use barrier contraception.
  • For 1st Line expansion cohort ONLY, confirmation that the tumour is EGFRm+ve and have had no prior therapy for their advanced disease (for 1st line patients biopsy will be at time of diagnosis of advanced disease).
  • For dose expansion and extension cohorts, patients must also have confirmation of tumour T790M mutation status (confirmed positive or negative) from a biopsy sample taken after disease progression on the most recent treatment regimen (irrespective of whether this is EGFR TKI or chemotherapy).

Prior to entry a result from the central analysis of the patient's T790M mutation status must be obtained.

- World Health Organisation (WHO) performance status 0-1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks.

Exclusion Criteria:

  • Treatment with an EGFR TKI (erlotinib or gefitinib) within 8 days (approximately 5x half-life) of the first dose of study treatment.
  • Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from the treatment of advanced NSCLC from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment.
  • AZD9291 in the present study (ie, dosing with AZD9291 previously initiated in this study).
  • Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection.
  • Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01802632

Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AstraZeneca Cancer Study Locator Service http://www.emergingmed.com/networks/AstraZeneca 1-877-400-4656 astrazeneca@emergingmed.com

  Show 42 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Serban Ghiorghiu, MSD AstraZeneca
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01802632     History of Changes
Other Study ID Numbers: D5160C00001
Study First Received: February 25, 2013
Last Updated: October 28, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Japan: Ministy of Health, Labor and Welfare
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Agencia Espanola de Medicamentos y Productos Sanitarios
Taiwan: Department of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by AstraZeneca:
Oncology,
Non Small Cell Lung Cancer,
Metastatic,
EGFR sensitivity mutation,
T790M resistance mutation

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms

ClinicalTrials.gov processed this record on November 27, 2014