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A Molecular Profiling Study of Patients With EGFR Mutation-positive Locally Advanced or Metastatic NSCLC Treated With Osimertinib (ELIOS)

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: NCT03239340
Recruitment Status : Active, not recruiting
First Posted : August 4, 2017
Last Update Posted : October 20, 2021
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE July 27, 2017
First Posted Date  ICMJE August 4, 2017
Last Update Posted Date October 20, 2021
Actual Study Start Date  ICMJE May 30, 2018
Estimated Primary Completion Date January 14, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 8, 2019)
Proportion of patients with a given tumour genetic and proteomic marker at the point of disease progression as defined by the Investigator [ Time Frame: Tumour Genetic and Proteomic markers will be assessed from tissue samples collected prior to initiation of treatment and at the time of disease progression for max 4.2 years ]
To characterize the frequency of genetic and proteomic markers at disease progression regardless of their prevalence.
Original Primary Outcome Measures  ICMJE
 (submitted: August 1, 2017)
Proportion of patients with a given genetic and proteomic marker at the point of disease progression as defined by the Investigator [ Time Frame: Genetic and Proteomic markers will be assessed from tissue samples collected prior to initiation of treatment and at the time of disease progression for up to 4 years ]
To examine the genetic and proteomic profile at the point of disease progression in patients receiving osimertinib as first-line EGFR tyrosine kinase inhibitor therapy for EGFR mutation-positive locally advanced or metastatic non-small cell lung cancer compared to the profile prior to initiation of treatment
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 8, 2019)
  • Progression-free survival (PFS) [ Time Frame: At baseline and every 8 weeks from enrolment until disease progression or death or end of study for max 4.2 years ]
    PFS is defined as the time from first dose of osimertinib until the date of Investigator assessed RECIST 1.1-defined progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anticancer therapy prior to progression.
  • Objective Response Rate (ORR) [ Time Frame: At baseline and every 8 weeks from enrolment until disease progression or death or end of study for max 4.2 years ]
    ORR is defined as the number (%) of patients with at least one visit response of complete response or partial response that is confirmed at least 4 weeks later.
  • Duration of Response (DoR) [ Time Frame: From time of first documented response until date of documented progression or death in the absence of disease progression or end of study up to max 4.2 years ]
    DoR is defined as the time from the date of first documented response, (that is subsequently confirmed) until date of documented progression or death in the absence of disease progression, the end of response should coincide with the date of progression or death from any cause used for the PFS endpoint.
  • Time toTreatment Discontinuation or Death (TTD) [ Time Frame: At every visit from enrolment to end of treatment or death or end of study for max 4.2 years ]
    TTD is defined as the time from the date of first dose of osimertinib to the earliest of treatment discontinuation or death.
  • Time to first subsequent therapy or Death (TFST) [ Time Frame: At every visit from enrolment to start of first subsequent therapy or death or end of study for max 4.2 years ]
    TFST is defined as the time from the date of first dose of osimertinib to the earlier of the date of anticancer therapy start date following study treatment discontinuation, or death.
  • Disease Control Rate [ Time Frame: At baseline and every 8 weeks from enrolment until disease progression or death or end of study for max 4.2 years ]
    Percentage of patients who have a best overall response, complete response, partial response or stable disease.
  • PFS in patient subgroups defined by molecular profile [ Time Frame: At baseline and every 8 weeks from enrolment until disease progression or death or end of study for max 4.2 years ]
    PFS will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: Positive pre-treatment T790M mutation, epidermal growth factor receptor (EGFR) Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived circulating tumour deoxyribonucleic acid (ctDNA).
  • ORR in patient subgroups defined by molecular profile [ Time Frame: At baseline and every 8 weeks from enrolment until disease progression or death or end of study for max 4.2 years ]
    ORR will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: Positive pre-treatment T790M mutation, EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA.
  • TTD in patient subgroups defined by molecular profile [ Time Frame: At every visit from enrolment to start of first subsequent therapy or death or end of study for max 4.2 years ]
    TTD will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: Positive pre-treatment T790M mutation, EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA.
  • Tumour shrinkage/depth of response in patient subgroups defined by molecular profile [ Time Frame: At baseline and every 8 weeks from enrolment until disease progression or death or end of study for max 4.2 years ]
    Tumour shrinkage is defined as the best change from baseline in the sum of diameters of target lesions. Tumour shrinkage/depth of response will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: Positive pre-treatment T790M mutation, EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA.
  • Proportion of patients with pre-specified characteristics will be summarised by molecular profile [ Time Frame: At baseline ]
    The patient characteristics will include: gender (male/female), age (<65yrs/>65yrs), race (Asian/non Asian), and WHO Performance Status (0/1). These will be summarized by subgroups defined by molecular profile, including but not limited to: Positive pre-treatment T790M mutation, EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 1, 2017)
  • Progression-free survival (PFS) [ Time Frame: At baseline and every 8 weeks from enrolment until disease progression or death or end of study for up to 4 years ]
    PFS is defined as the time from first dose of osimertinib until the date of RECIST 1.1-defined progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anticancer therapy prior to progression.
  • Objective Response Rate (ORR) [ Time Frame: At baseline and every 8 weeks from enrolment until disease progression or death or end of study up to 4 years ]
    ORR is defined as the number (%) of patients with at least one visit response of complete response or partial response that is confirmed at least 4 weeks later.
  • Duration of Response (DoR) [ Time Frame: At baseline and every 8 weeks from enrolment until disease progression of death or end of study up to 4 years ]
    DoR is defined as the time from the date of first documented response, (that is subsequently confirmed) until date of documented progression or death in the absence of disease progression, the end of response should coincide with the date of progression or death from any cause used for the PFS endpoint.
  • Time to Treatment Discontinuation or Death (TTD) [ Time Frame: At every visit from enrolment to end of treatment or death or end of study up to 4 years ]
    TTD is defined as the time from the date of first dose of osimertinib to the earliest of treatment discontinuation or death.
  • Time to first subsequent therapy or Death (TFST) [ Time Frame: At every visit from enrolment to start of first subsequent therapy or death or end of study up to 4 years ]
    TFST is defined as the time from the date of first dose of osimertinib to the earlier of the date of anticancer therapy start date following study treatment discontinuation, or death.
  • Tumour shrinkage/ depth of response [ Time Frame: At baseline and every 8 weeks from enrolment until disease progression or death or end of study up to 4 years ]
    Tumour shrinkage is defined as the best change from baseline in the sum of diameters of target lesions
Current Other Pre-specified Outcome Measures
 (submitted: March 1, 2018)
Adverse events graded by Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: At every visit from signing informed consent until 28 days after last dose of study treatment ]
To summarize the safety and tolerability profile of osimertinib as first-line EGFR tyrosine kinase inhibitor therapy for patients with EGFR mutation-positive locally advanced or metastatic non-small cell lung cancer
Original Other Pre-specified Outcome Measures
 (submitted: August 1, 2017)
Adverse events graded by Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: At every visit from signing informed consent until 28 days after last dose of study treatment up to 4 years ]
To summarize the safety and tolerability profile of osimertinib as first-line EGFR tyrosine kinase inhibitor therapy for patients with EGFR mutation-positive locally advanced or metastatic non-small cell lung cancer
 
Descriptive Information
Brief Title  ICMJE A Molecular Profiling Study of Patients With EGFR Mutation-positive Locally Advanced or Metastatic NSCLC Treated With Osimertinib
Official Title  ICMJE A Multicentre, Open-label, Single-arm, Molecular Profiling Study of Patients With EGFR Mutation-positive Locally Advanced or Metastatic NSCLC Treated With Osimertinib
Brief Summary A multicentre, open-label, single-arm, molecular profiling study of patients with EGFR mutation-positive locally advanced or metastatic NSCLC treated with osimertinib.
Detailed Description Study design This is a phase II, open-label, single-arm tissue and plasma acquisition study assessing the efficacy, safety and underlying resistance mechanisms of osimertinib (80 mg orally, once daily) as first-line treatment in patients with locally advanced or metastatic EGFR mutation positive non-small cell lung cancer who are EGFR tyrosine kinase inhibitor treatment-naïve and eligible for first-line treatment. Participants with EGFR mutation-positive non-small cell lung cancer will be required to consent to 2 mandatory tumour biopsies to be considered for enrolment in this study. The first biopsy will be done prior to initiating treatment with osimertinib and the second biopsy will be obtained any time between Investigator assessed, Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1)-defined progression and up to 7 days after the discontinuation of osimertinib. A third optional biopsy may be taken during the course of treatment at the Investigator's discretion if the patient consents and if clinically feasible. Tumour tissue and plasma samples will be collected and examined for genetic and non genetic aberrations that may be important in determining response and resistance to the treatment that participants will receive as a part of their cancer care. Patients should continue on osimertinib until progression or until other treatment discontinuation criteria are met. However, if patients continue to show clinical benefit to treatment as judged by the Investigator, patients may continue to receive osimertinib beyond RECIST 1.1-defined progression. Therefore, there is no maximum duration of treatment. Tumour assessments are to be performed at baseline and then every 8 weeks until progression. Patients will be followed up for a period of 28 days following discontinuation of osimertinib. Target patient population Male and female patients aged 18 years and over with locally advanced or metastatic pathologically confirmed adenocarcinoma of the lung, not amenable to curative surgery or radiotherapy. Patients will have a tumour that harbours one of the EGFR mutations known to be associated with EGFR tyrosine kinase inhibitor sensitivity, either alone or in combination with other EGFR mutations (EGFR mutation status determined by a local laboratory). Patients must be EGFR tyrosine kinase inhibitor treatment-naïve and eligible to receive first line treatment with osimertinib. Osimertinib is an oral, potent, selective, irreversible inhibitor of both EGFR tyrosine kinase inhibitor sensitizing and resistance mutations in non-small cell lung cancer with a significant selectivity margin over wild type EGFR. Osimertinib (80 mg orally, once daily) will be administered. Doses may be reduced to 40 mg if needed.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE EGFR Mutation Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Intervention  ICMJE Drug: Osimertinib
Osimertinib is an oral, potent, selective, irreversible inhibitor of both EGFR tyrosine kinase inhibitor sensitizing and resistance mutations in non-small cell lung cancer with a significant selectivity margin over wild type EGFR.
Other Name: TAGRISSO, AZD9291
Study Arms  ICMJE Experimental: Osimertinib
An oral, potent, selective, irreversible inhibitor of both EGFR tyrosine kinase inhibitor sensitizing and resistance mutations in non-small cell lung cancer
Intervention: Drug: Osimertinib
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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 29, 2019)
154
Original Estimated Enrollment  ICMJE
 (submitted: August 1, 2017)
100
Estimated Study Completion Date  ICMJE October 16, 2022
Estimated Primary Completion Date January 14, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Provision of informed consent prior
  2. Patients aged 18 years or older
  3. Patients with histological confirmation of locally advanced or metastatic NSCLC
  4. Patients with M1 stage according to the Tumor, Node and Metastasis Classification of Malignant Tumours (TNM)
  5. Patients with an EGFR deletion or mutation known (from tumour biopsy or plasma) to be associated with EGFR TKI sensitivity
  6. Existence of measurable or evaluable disease (as per RECIST 1.1 criteria).
  7. Possibility of obtaining sufficient tissue sample, via a biopsy or surgical resection of the primary tumour or metastatic tumour tissue
  8. WHO performance status 0-1
  9. Life expectancy ≥12 weeks
  10. Capacity to swallow
  11. Patients able to complete study and within geographical proximity allowing for adequate follow up
  12. Resolution of all acute toxic effects of previous anticancer therapy
  13. Female patients should be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of childbearing potential
  14. Male patients should be willing to use barrier contraception

Exclusion Criteria:

  1. Locally advanced lung cancer candidate for curative treatment through radical surgery and/or radio(chemo)therapy
  2. Patients diagnosed with another lung cancer subtype
  3. Patients with an EGFR exon 20 insertion
  4. Patients with just one measurable or evaluable tumour lesion that has been resected or irradiated prior to their enrolment in the study
  5. Second active neoplasia
  6. Treatment with an investigational drug within five half-lives of the compound
  7. Participation in another clinical study with an investigational product (IP) during the last 3 weeks before the first day of study treatment
  8. Patients who have received prior immunotherapies
  9. Patients who have received prior EGFR treatments for lung cancer
  10. Patients who have received prior treatment with an EGFR TKI including in the adjuvant setting
  11. Patients who have received previous treatment for metastatic or stage IV disease
  12. Prior treatment with cytotoxic chemotherapy for advanced NSCLC
  13. Patients with a history of cancer that has been completely treated, with no evidence of malignant disease currently cannot be enrolled in the study if their chemotherapy was completed less than 6 months prior and/or have received a bone marrow transplant less than 2 years before the first day of study treatment
  14. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy
  15. Any evidence of severe or uncontrolled systemic diseases
  16. Patients who have had a surgical procedure unrelated to the study within 14 days or major surgery within 1 month prior to the administration of the study drug
  17. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis
  18. Any of the following cardiac criteria: Mean resting QT interval corrected for heart rate (QTc) more than 470 msec, obtained from 3 ECGs, using the screening clinic ECG machine derived QTc value. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval
  19. Spinal cord compression, symptomatic and unstable brain metastases except for those patients who have completed definitive therapy, and have had a stable neurological status for at least 2 weeks after completion of definitive therapy. 20.Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib

21.Inadequate bone marrow reserve or organ function 22.Female patients who are breastfeeding 23.Patients currently receiving medications or herbal supplements known to be potent inducers of cytochrome P450 24.Patient unwilling to undergo a biopsy at the time of disease progression 25.History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib 26.Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements 27.Involvement in the planning and/or conduct of the study 28.Previous enrolment in the present study

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 Italy,   Korea, Republic of,   Malaysia,   Spain,   United States
Removed Location Countries Austria
 
Administrative Information
NCT Number  ICMJE NCT03239340
Other Study ID Numbers  ICMJE D5161C00003
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Parexel
Investigators  ICMJE
Principal Investigator: Zosia Piotrowska, MD Massachusetts General Hospital
PRS Account AstraZeneca
Verification Date October 2021

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