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AZD9291 First Time In Patients Ascending Dose Study (AURA)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01802632
First received: February 25, 2013
Last updated: August 12, 2016
Last verified: August 2016
  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: 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:
  • Objective Response Rate (ORR) for Dose Expansion Population [ Time Frame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 21 months (at time of analysis) ] [ Designated as safety issue: No ]
    Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. ORR is the percentage of patients with at least 1 visit response of CR or PR (by investigator assessment) that was confirmed at least 4 weeks later, prior to progression or further anti-cancer therapy.

  • Best Objective Response (BOR) for Dose Escalation Population [ Time Frame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 25 months (at time of analysis) ] [ Designated as safety issue: No ]
    Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions; Stable disease (SD): Neither sufficient shrinkage to qualify as a response nor sufficient growth to qualify as progression; Progressive Disease (PD): >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. Not evaluable (NE): TL response is missing and there is no evidence of progression of NTLs and no new lesions. BOR is the best response (by investigator assessment) a patient has achieved where the order of best to worst is CR, PR, SD, PD, NE prior to or at progression and prior to further anti-cancer therapy.

  • Objective Response Rate (ORR) for Extension Population [ Time Frame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 12 months (at the time of analysis) ] [ Designated as safety issue: No ]
    Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. ORR is the percentage of patients with at least 1 visit response of CR or PR (by independent central review) that was confirmed at least 4 weeks later, prior to progression or further anti-cancer therapy.


Secondary Outcome Measures:
  • Duration of Response (DoR) for Dose Expansion Population [ Time Frame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 21 months (at time of analysis) ] [ Designated as safety issue: No ]
    Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. DoR was defined as the time from the date of first documented response (CR or PR that was subsequently confirmed) until the date of documented progression (PD) or death in the absence of disease progression (by investigator assessment).

  • Progression-Free Survival (PFS) for Dose Expansion Population [ Time Frame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 21 months (at time of analysis) ] [ Designated as safety issue: No ]
    Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Progressive Disease (PD): >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. PFS is the time from date of first dose until the date of PD (by independent central review) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from AZD9291 therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST 1.1 assessment.

  • Best Objective Response (BOR) for 80mg AZD9291 Extension Population [ Time Frame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 12 months (at the time of analysis) ] [ Designated as safety issue: No ]
    Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions; Stable disease (SD): Neither sufficient shrinkage to qualify as a response nor sufficient growth to qualify as progression; Progressive Disease (PD): >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. Not evaluable (NE): TL response is missing and there is no evidence of progression of NTLs and no new lesions. BOR is the best response (by investigator assessment) a patient has achieved where the order of best to worst is CR, PR, SD, PD, NE prior to or at progression and prior to further anti-cancer therapy.


Enrollment: 974
Study Start Date: March 2013
Estimated Study Completion Date: November 2016
Primary Completion Date: May 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 to 130 Years   (Adult, Senior)
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

  Show 41 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Serban Ghiorghiu, MSD AstraZeneca
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01802632     History of Changes
Other Study ID Numbers: D5160C00001 
Study First Received: February 25, 2013
Results First Received: April 29, 2016
Last Updated: August 12, 2016
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:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Osimertinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 08, 2016