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Real World Treatment Study of AZD9291 for Advanced/Metastatic EGFR T790M Mutation NSCLC (ASTRIS)

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ClinicalTrials.gov Identifier: NCT02474355
Recruitment Status : Completed
First Posted : June 17, 2015
Last Update Posted : March 17, 2020
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE May 27, 2015
First Posted Date  ICMJE June 17, 2015
Last Update Posted Date March 17, 2020
Actual Study Start Date  ICMJE September 18, 2015
Actual Primary Completion Date April 19, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 15, 2015)
  • Efficacy of AZD9291 by the analysis of overall survival. [ Time Frame: From first dose intake to end of study (Last subject last visit (LSLV)) (up to approximately 24 months) ]
    Efficacy will be measured by the analysis of Overall Survival defined as the date of 1st dose until date of death.
  • Safety of AZD9291 by assessment of Serious Adverse Events, Adverse Events of special interest (Interstitial Lung Disease/pneumonitis-like events, Cardiac events) [ Time Frame: Patient receiving at least one dose until 30 days post last dose of AZD9291 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2015)
Efficacy of AZD9291 by the analysis of Progression Free Survival (PFS) [ Time Frame: from first dose intake to progression or death. ]
PFS will be summarized using Kaplan-Meier estimates of the median time to progression or death and quartiles with their 95% confidence intervals.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Real World Treatment Study of AZD9291 for Advanced/Metastatic EGFR T790M Mutation NSCLC
Official Title  ICMJE Open Label, Multinational, Multicenter, Real World Treatment Study of Single Agent AZD9291 for Patients With Advanced/Metastatic Epidermal Growth Factor Receptor (EGFR) T790M Mutation-Positive Non-Small Cell Lung Cancer (NSCLC) Who Have Received Prior Therapy With an EGFR Tyrosine Kinase Inhibitor (EGFR-TKI)
Brief Summary The aim of this study is to assess the efficacy and safety of single agent AZD9291 in a real world setting in adult patients with advanced or metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer (NSCLC), who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy.
Detailed Description

Objective: The primary objective of this study is to assess the efficacy and safety of single agent AZD9291 in a real world setting in adult patients with advanced or metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer (NSCLC), who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy.

Study site(s) and number of patients planned: Approximately 1500 patients will be recruited in Europe. The recruitment will be increased beyond that as the study will expand in other regions of the world (America, Asia).

Study Design This will be an open-label, single-arm, multinational, multicenter, real world treatment study.

Target patient population: Adult patients (fulfilling the definition of "age of majority" per local regulations) with locally advanced (stage IIIB) or metastatic (stage IV) NSCLC with confirmed T790M mutation, who have received prior EGFR-TKI therapy.

Investigational product (IP), dosage, and mode of administration: AZD9291 is an oral, potent, selective, irreversible inhibitor of both EGFR-TKI sensitising and resistance mutations in NSCLC with a significant selectivity margin over wild-type EGFR. AZD9291 will be administered orally as one 80 mg tablet once a day.

Duration of IP administration: Patients may continue to receive AZD9291 as long as they continue to show clinical benefit, as judged by the investigator, and in the absence of discontinuation criteria). The study will be closed in each participating country as soon as possible following national reimbursement of AZD9291 in that country (up to a max of 90 days post reimbursement). Enrolment will be closed within 6 months after market license approval in that country or at national reimbursement, whichever is sooner. Patients withdrawing from the treatment prior to national reimbursement will be followed up as part of this study. Patients on treatment will receive commercial supply until documented disease progression as per investigator assessment.

In the event that national reimbursement should not be granted following a reasonable time after market license approval in the country, the study will be closed in a maximum period of 18 months after the last patient is enrolled in that country. If applicable, timelines for conversion to commercial drug will be agreed with local bodies which may include regulatory agencies, ethics committees, and institutions. Patient will be followed until death or lost to follow-up.

Study measures: Data collected will include patient demographics, information needed to determine patient eligibility (including medical history, past and current disease characteristics, and tumor EGFR mutational status), AZD9291 exposure, investigator-reported efficacy (including tumor response and disease progression), overall survival (OS), and safety (including serious adverse events [SAEs], adverse events leading to dose modification, and adverse events of special interest [interstitial lung disease/pneumonitis-like events, and QTc prolongation events]).

Statistical methods: All data will be presented for the overall full analysis/evaluable set, and also by cohorts defined by number and type of previous treatment lines for the advanced disease. Descriptive statistics will be used for all variables, as appropriate. Continuous variables will be summarised by the number of observations, mean, standard deviation, median, minimum, and maximum. Categorical variables will be summarised by frequency counts and percentages for each category. OS and PFS will be summarized using Kaplan-Meier estimates of the median time to death or censoring and quartiles together with their 95% confidence intervals.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lung Cancer
Intervention  ICMJE
  • Procedure: T790M+ Testing
    If a previous lab report is unavailable, the patient will need to have T790M+ testing.
  • Procedure: Baseline Visit Blood & Urine Testing
    Blood count and standard chemistry testing to ensure patient meets inclusion/exclusion criteria
  • Procedure: Baseline ECG
    ECG to ensure absence of any cardiac abnormality
  • Procedure: Visual Slit-Lamp Testing
    Slit-lamp testing performed to ensure patients do not have any eye abnormalities or symptoms
  • Drug: AZD9291 Dosing
    Patients to be provided with AZD9291 every 6 weeks (+/- 7 days)
Study Arms  ICMJE Experimental: AZD9291
Single arm of AZD9291, starting dose of 80mg
Interventions:
  • Procedure: T790M+ Testing
  • Procedure: Baseline Visit Blood & Urine Testing
  • Procedure: Baseline ECG
  • Procedure: Visual Slit-Lamp Testing
  • Drug: AZD9291 Dosing
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 7, 2017)
3020
Original Estimated Enrollment  ICMJE
 (submitted: June 15, 2015)
2550
Actual Study Completion Date  ICMJE April 19, 2019
Actual Primary Completion Date April 19, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Provision of signed and dated written informed consent by the patient or legally acceptable representative prior to any study-specific procedures
  2. Adults (according to each country regulations for age of majority)
  3. Locally advanced (stage IIIB) or metastatic (stage IV) EGFRm NSCLC, not amenable to curative surgery or radiotherapy, with confirmation of the presence of the T790M mutation
  4. Prior therapy with an EGFR-TKI. Patients may have also received additional lines of treatment
  5. World Health Organization (WHO) performance status 0-2
  6. Adequate bone marrow reserve and organ function as demonstrated by complete blood count, biochemistry in blood and urine at baseline (please refer to IB for guidance)
  7. ECG recording at baseline showing absence of any cardiac abnormality as per exclusion criterion #6
  8. Female patients of childbearing potential must be using adequate contraceptive measures, must not be breast feeding, and must have a negative pregnancy test prior to start of dosing. Otherwise, they must have evidence of nonchildbearing potential
  9. Male patients must be willing to use barrier contraception, i.e., condoms

Exclusion Criteria:

  1. Previous (within 6 months) or current treatment with AZD9291
  2. Patients currently receiving (or unable to stop use at least 1 week prior to receiving the first dose of AZD9291) any treatment known to be potent inhibitors or inducers of cytochrome P450 (CYP) 3A4
  3. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, active infection including hepatitis B, hepatitis C, and human immunodeficiency virus, or significantly impaired bone marrow reserve or organ function, including hepatic and renal impairment, which in the investigator's opinion would significantly alter the risk/benefit balance.
  4. Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids to manage CNS symptoms within the 2 weeks prior to start AZD9291 administration;
  5. Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
  6. Any of the following cardiac criteria:

    1. Mean resting corrected QT interval (QTcF) > 470 ms using Fredericia's formula :
    2. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block)
    3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
  7. Any unresolved toxicity from prior therapy CTCAE > grade 3 at the time of starting treatment
  8. History of hypersensitivity to excipients of AZD9291 or to drugs with a similar chemical structure or class to AZD9291
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   China,   Denmark,   Ireland,   Italy,   Korea, Republic of,   Saudi Arabia,   Spain,   Sweden,   Taiwan,   United Arab Emirates,   United Kingdom
Removed Location Countries Finland,   Mexico,   Netherlands,   Norway,   Switzerland
 
Administrative Information
NCT Number  ICMJE NCT02474355
Other Study ID Numbers  ICMJE D5160C00022
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Parexel
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP