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Lung NeoplasmsPhase 2LiquidLung-ONCT02769286

Osimertinib in First and Second Line Treatment of NSCLC Harboring EGFR Mutations From Circulating Tumor DNA

A Phase 2 study testing Osimertinib in people with Lung Neoplasms and EGFR Gene Mutations, run by Chonnam National University Hospital at 1 site in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Treatment efficacy of osimertinib will be assessed in patients with lung cancer harboring activating epidermal growth factor receptor (EGFR) mutations (cohort 1) and those harboring T790M (cohort 2) which were detected from circulating tumor DNA Read more about this study

Who is it for?
Ages 19 years and older
Conditions the study is for
Lung Neoplasms, EGFR Gene Mutations
What is being tested?
Osimertinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
1 siteSouth Korea
Study dates
Aug 2016to May 2020
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • < Cohort 1 >
  • Provision of informed consent prior to any study specific procedures
  • Patients (male/female) must be > 18 years of age.
  • Locally advanced or metastatic non-small cell lung cancer, not amenable to curative surgery or radiotherapy with or without pathologic diagnosis
  • No prior exposure to EGFR TKI (multiple lines of prior cytotoxic chemotherapy are permitted.)
  • Activating EGFR mutation (G719X, exon 19 deletion, L858R, L861Q) detected from circulating tumor DNA either by PANA mutyper® or Cobas® EGFR mutation test.
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  • Activating EGFR mutation (G719X, exon 19 deletion, L858R, L861Q) detected from tumor tissue or cytology specimen.
  • World Health Organization (WHO) performance status 0-2.
  • Patients must have a life expectancy ≥ 12 weeks.
  • Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
  • Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
  • Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for the institution
  • Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
  • Male patients should be willing to use barrier contraception.
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT)
  • < Cohort 2 >
  • Provision of informed consent prior to any study specific procedures
  • Patients (male/female) must be > 18 years of age.
  • Locally advanced or metastatic non-small cell lung cancer, not amenable to curative surgery or radiotherapy with or without pathologic diagnosis
  • Progression after prior exposure to gefitinib, erlotinib, afatinib or dacomitinib. Multiple lines of prior cytotoxic chemotherapy are permitted and there is no specified order of treatment.
  • Patients must fulfil one of the following:
  • 5.1) Activating EGFR mutation (G719X, exon 19 deletion, L858R, L861Q) from tumor tissue or cytology or circulating tumor DNA 5.2) Must have experienced clinical benefit from prior EGFR-TKI, according to the Jackman criteria (Jackman 2010) followed by systemic objective progression (RECIST) while on continuous treatment with EGFR-TKI
  • T790M mutation detected from circulating tumor DNA either by PANA mutyper® or Cobas® EGFR mutation test.
  • World Health Organization (WHO) performance status 0-2.
  • Patients must have a life expectancy ≥ 12 weeks.
  • Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
  • Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
  • Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution
  • Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
  • Male patients should be willing to use barrier contraception.
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT)

Who cannot join

  • Previous treatment with AZD9291, or other 3rd generation EGFR TKI
  • Treatment with an investigational drug within five half-lives of the compound
  • Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inhibitors of CYP3A4 (at least 1 week prior) and potent inducers of CYP3A4 (at least 3 week prior) (Appendix A). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer/inhibitory effects on CYP3A4.
  • Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy.
  • Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
  • Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable
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  • Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
  • Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
  • Absolute neutrophil count <1.5 x 109/L Platelet count <100 x 109/L Haemoglobin <90 g/L Alanine aminotransferase >2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases Aspartate aminotransferase >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases Total bilirubin >1.5 times ULN if no liver metastases or >3 times ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or liver metastases Creatinine >1.5 times ULN concurrent with creatinine clearance <50 ml/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN.
  • Any of the following cardiac criteria:
  • Mean resting corrected QT interval (QTc using Fredericia's formula) > 470 msec
  • 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)
  • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, 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
  • Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD9291
  • History of hypersensitivity to AZD9291 (or drugs with a similar chemical structure or class to AZD9291) or any excipients of these agents
  • Males and females of reproductive potential who are not using an effective method of birth control and females who are pregnant or breastfeeding or have a positive (urine or serum) pregnancy test prior to study entry
  • 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
  • Previous allogeneic bone marrow transplant.
  • Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.

Trial locations and contacts

1 site in 1 country.

South Korea1 site

  • Chonnam National University Hwasun Hospital

    Hwasun, Jeollanam-do, 58128

Other trials in South Korea

About this study

Official title: Phase II Trial of AZD9291 in First Line Treatment of Lung Cancer Harboring Activating EGFR Mutation From Circulating Tumor DNA and Second Line Treatment After Acquired Resistance With T790M Mutation Detected From Circulating Tumor DNA

Treatment efficacy of osimertinib will be assessed in patients with lung cancer harboring activating epidermal growth factor receptor (EGFR) mutations (cohort 1) and those harboring T790M (cohort 2) which were detected from circulating tumor DNA

Read the detailed description

This is a phase II, open-label, single centre study of AZD9291 administered orally in patients with advanced lung cancer with activating mutations of EGFR gene with or without T790M which were detected from circulating tumor DNA. EGFR-TKI naïve patients with activating EGFR mutation will be enrolled in cohort 1. Patients with acquired resistance to prior EGFR tyrosine kinase inhibitor (TKI) due to T790M mutation is going to be enrolled in cohort 2.

Being tested
Osimertinib
Medical subject headings
Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OsimertinibDrug

    Also called AZD9291

    Treatment efficacy of osimertinib will be assessed in patients with lung cancer harboring EGFR mutations (cohort 1) and those harboring T790M (cohort 2) which were detected from circulating tumor DNA

Study groups in NCT02769286
Study groupRoleWhat they receive
Osimertinib in cohort 1ExperimentalTreatment efficacy of osimertinib will be assessed in patients with lung cancer harboring EGFR mutations which were detected from circulating tumor DNA
Receives: Drug: Osimertinib
Osimertinib in cohort 2ExperimentalTreatment efficacy of osimertinib will be assessed in patients with lung cancer harboring T790M which were detected from circulating tumor DNA
Receives: Drug: Osimertinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Response rate

    RECIST v1.1

    Measured: 2 months

Secondary outcomes (4)

  1. Sensitivity of testing methods

    Percentage of positive cases among cases tested with Mutyper or Cobas

    Measured: 2 weeks

  2. Progression free survival

    Measured: 2 years

  3. Duration of response

    Measured: 2 years

  4. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 May 2016 (estimated)
  2. Study startAug 2016
  3. Primary completionDec 2018
  4. Study completionMay 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02769286
Sponsor's protocol ID
ESR-15-11075
Acronym
LiquidLung-O
Status last verified
Aug 2021
First submitted
9 May 2016
Last updated
3 Aug 2021
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Janne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam SS, Ahn MJ, Kim SW, Su WC, Horn L, Haggstrom D, Felip E, Kim JH, Frewer P, Cantarini M, Brown KH, Dickinson PA, Ghiorghiu S, Ranson M. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med. 2015 Apr 30;372(18):1689-99. doi: 10.1056/NEJMoa1411817.

    PubMed 25923549

  • Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. doi: 10.1200/JCO.2012.44.2806. Epub 2013 Jul 1.

    PubMed 23816960

  • Jackman D, Pao W, Riely GJ, Engelman JA, Kris MG, Janne PA, Lynch T, Johnson BE, Miller VA. Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J Clin Oncol. 2010 Jan 10;28(2):357-60. doi: 10.1200/JCO.2009.24.7049. Epub 2009 Nov 30.

    PubMed 19949011

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Osimertinib in people with Lung Neoplasms and EGFR Gene Mutations, run by Chonnam National University Hospital at 1 site in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 33 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response rate (time frame: 2 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02769286, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2021.

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