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Osimertinib in First and Second Line Treatment of NSCLC Harboring EGFR Mutations From Circulating Tumor DNA (LiquidLung-O)

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: NCT02769286
Recruitment Status : Unknown
Verified July 2018 by Young-Chul Kim, Chonnam National University Hospital.
Recruitment status was:  Active, not recruiting
First Posted : May 11, 2016
Last Update Posted : July 18, 2018
Sponsor:
Information provided by (Responsible Party):
Young-Chul Kim, Chonnam National University Hospital

Brief 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

Condition or disease Intervention/treatment Phase
Lung Neoplasms EGFR Gene Mutations Drug: Osimertinib Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Osimertinib in cohort 1
Treatment efficacy of osimertinib will be assessed in patients with lung cancer harboring EGFR mutations which were detected from circulating tumor DNA
Drug: Osimertinib
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
Other Name: AZD9291

Experimental: Osimertinib in cohort 2
Treatment efficacy of osimertinib will be assessed in patients with lung cancer harboring T790M which were detected from circulating tumor DNA
Drug: Osimertinib
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
Other Name: AZD9291




Primary Outcome Measures :
  1. Response rate [ Time Frame: 2 months ]
    RECIST v1.1


Secondary Outcome Measures :
  1. Sensitivity of testing methods [ Time Frame: 2 weeks ]
    Percentage of positive cases among cases tested with Mutyper or Cobas

  2. Progression free survival [ Time Frame: 2 years ]
  3. Duration of response [ Time Frame: 2 years ]
  4. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 2 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

< Cohort 1 >

  1. Provision of informed consent prior to any study specific procedures
  2. Patients (male/female) must be > 18 years of age.
  3. Locally advanced or metastatic non-small cell lung cancer, not amenable to curative surgery or radiotherapy with or without pathologic diagnosis
  4. No prior exposure to EGFR TKI (multiple lines of prior cytotoxic chemotherapy are permitted.)
  5. Activating EGFR mutation (G719X, exon 19 deletion, L858R, L861Q) detected from circulating tumor DNA either by PANA mutyper® or Cobas® EGFR mutation test.
  6. Activating EGFR mutation (G719X, exon 19 deletion, L858R, L861Q) detected from tumor tissue or cytology specimen.
  7. World Health Organization (WHO) performance status 0-2.
  8. Patients must have a life expectancy ≥ 12 weeks.
  9. 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
  10. Male patients should be willing to use barrier contraception.
  11. 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.
  12. 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 >

  1. Provision of informed consent prior to any study specific procedures
  2. Patients (male/female) must be > 18 years of age.
  3. Locally advanced or metastatic non-small cell lung cancer, not amenable to curative surgery or radiotherapy with or without pathologic diagnosis
  4. 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.
  5. 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

  6. T790M mutation detected from circulating tumor DNA either by PANA mutyper® or Cobas® EGFR mutation test.
  7. World Health Organization (WHO) performance status 0-2.
  8. Patients must have a life expectancy ≥ 12 weeks.
  9. 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
  10. Male patients should be willing to use barrier contraception.
  11. 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.
  12. 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)

Exclusion Criteria:

  1. Previous treatment with AZD9291, or other 3rd generation EGFR TKI
  2. Treatment with an investigational drug within five half-lives of the compound
  3. 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.
  4. 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.
  5. 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.
  6. Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable
  7. Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
  8. 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.

  9. Any of the following cardiac criteria:

    1. Mean resting corrected QT interval (QTc using Fredericia's formula) > 470 msec
    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 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
  10. 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
  11. History of hypersensitivity to AZD9291 (or drugs with a similar chemical structure or class to AZD9291) or any excipients of these agents
  12. 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
  13. 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
  14. Previous allogeneic bone marrow transplant.
  15. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.

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): NCT02769286


Locations
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Korea, Republic of
Chonnam National University Hwasun Hospital
Hwasun, Jeonnam, Korea, Republic of, 58128
Sponsors and Collaborators
Chonnam National University Hospital
Investigators
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Principal Investigator: Young-Chul Kim, MD, PhD Chonnam National University Hospital
Publications:
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Responsible Party: Young-Chul Kim, Professor, Chonnam National University Hospital
ClinicalTrials.gov Identifier: NCT02769286    
Other Study ID Numbers: ESR-15-11075
First Posted: May 11, 2016    Key Record Dates
Last Update Posted: July 18, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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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