ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    ASTRIS D5160C00022
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02474355
Recruitment Status : Active, not recruiting
First Posted : June 17, 2015
Last Update Posted : February 11, 2019
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease Intervention/treatment Phase
Lung Cancer Procedure: T790M+ Testing Procedure: Baseline Visit Blood & Urine Testing Procedure: Baseline ECG Procedure: Visual Slit-Lamp Testing Drug: AZD9291 Dosing Phase 3

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 : Interventional  (Clinical Trial)
Actual Enrollment : 3020 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : September 18, 2015
Estimated Primary Completion Date : April 9, 2019
Estimated Study Completion Date : April 9, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Osimertinib

Arm Intervention/treatment
Experimental: AZD9291
Single arm of AZD9291, starting dose of 80mg
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)




Primary Outcome Measures :
  1. 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.

  2. 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 ]

Secondary Outcome Measures :
  1. 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.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02474355


  Show 202 Study Locations
Sponsors and Collaborators
AstraZeneca
Parexel

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02474355     History of Changes
Other Study ID Numbers: D5160C00022
First Posted: June 17, 2015    Key Record Dates
Last Update Posted: February 11, 2019
Last Verified: February 2019

Keywords provided by AstraZeneca:
NSCLC
EGFRm
T790M

Additional relevant MeSH terms:
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Osimertinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action