Clinical Trials /

TAGRISSO (Osimertinib) in NSCLC Patients in Whom T790 Mutations Are Detected by Liquid Biopsy Using BALF, Plasma or Pleural Effusion

NCT03394118

Description:

In this trial, anti-tumor efficacy of TAGRISSO in NSCLC patients in whom T790 mutations are detected by liquid biopsy.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: TAGRISSO (Osimertinib) in NSCLC Patients in Whom T790 Mutations Are Detected by Liquid Biopsy Using BALF, Plasma or Pleural Effusion
  • Official Title: A Phase II Study for Evaluating Anti-tumor Efficacy of TAGRISSO (Osimertinib) in NSCLC Patients in Whom T790 Mutations Are Detected by Liquid Biopsy Using Bronchoalveolar Lavage Fluid, Plasma or Pleural Effusion

Clinical Trial IDs

  • ORG STUDY ID: C2016-00578_ESR-16-11898
  • NCT ID: NCT03394118

Conditions

  • NSCLC

Interventions

DrugSynonymsArms
OsimertinibGroup_TAGRISSO

Purpose

In this trial, anti-tumor efficacy of TAGRISSO in NSCLC patients in whom T790 mutations are detected by liquid biopsy.

Detailed Description

      This study is designed to be a phase II, Open-label, single-arm, single-center study to
      evaluate anti-tumor efficacy of TAGRISSO in NSCLC patients in whom T790 mutations are
      detected by liquid biopsy using at least one of the samples such as plasma, bronchoalveolar
      lavage fluid, and pleural effusion. Approximately 63 patients will be enrolled into the
      trial, and expected study duration is 24 months from IRB and Korea: MFDA approval date.

      Each subject will continue the study drug (Osimertinib) until disease progression or
      manifestation of unacceptable toxicity during the study period. The study drug will be
      administered orally as one 80 mg tablet once a day. The initial dose of the study drug 80 mg
      daily can be reduced to 40 mg once daily.

      A cycle of study treatment is defined as 28 days. Patients will be enrolled for 12 months and
      will be followed-up regularly, and duration of follow-up for each patient will be 12 months.
    

Trial Arms

NameTypeDescriptionInterventions
Group_TAGRISSOExperimentalEach subject will continue the study drug(Osimertinib) until disease progression or manifestation of unacceptable toxicity during the study period. The study drug will be administered orally as one 80 mg tablet once a day. The initial dose of the study drug 80 mg daily can be reduced to 40 mg once daily.
  • Osimertinib

Eligibility Criteria

        Inclusion Criteria:

          1. Age ≥ 20, and patients who understand information about the trial and voluntarily
             agree to participate in the trial

          2. Histological or cytological confirmation diagnosis of NSCLC and inoperable stage IIIB
             or IV at the time of study enrolment

          3. Patients with EGFR sensitizing mutation (E19Del, L858R, L861Q, G719X) positive, who
             had shown clinical benefits (responders (CR or PR) and SD ≥6 months) from EGFR-TKIs
             and had developed progressive disease following those therapy

               -  Patients who have histories of previous exposure to EGFR-TKIs or other systemic
                  chemotherapies are permitted (regardless of the order of treatment)

               -  Treated with at least one of KGFR-TKIs (regardless of treatment with or without
                  systemic chemotherapies)

               -  In case the patient previously received any of the treatments including systemic
                  chemotherapy, radiation therapy, surgery, and hormonal therapy, there should be
                  at least 2 weeks of time interval between the last day of the previous treatment
                  and the start of TAGRISSO™, and the remaining toxicity should be ≤ CTCAE grade 1
                  at the time of starting study treatment (except alopecia and grade 2, prior
                  platinum-therapy related neuropathy)

          4. ECOG performance status 0-2

          5. Patients in whom T790 mutations are detected in at least one of the samples including
             tumor tissues, BALF (cell-free DNA), plasma (cell-free DNA), and pleural effusion
             (cell-free DNA)

          6. At least one measurable lesions according to RECIST v 1.1

          7. Female with childbearing potential (within 1 year of time interval between last menses
             and the date of informed consent) who use appropriate contraception methods and are
             not on breast-feeding, and tested negative for pregnancy test or are sure to have a
             proof for infertility prior to drug initiation

          8. Males willing to use barrier contraception methods during study period (Patients
             should inform their sexual partners of the use of the allowed contraception methods.)

          9. Patients willing to provide informed consent with date and signature included prior to
             all study-specific procedures, samplings and analyse

         10. Patients who have proper organ functions as follows:

               -  ANC ≥ 1500/mm3,

               -  PLT counts ≥ 100,000/mm3,

               -  Hb ≥ 9.0g/dL,

               -  Serum creatinine ≤ upper normal limit,

               -  AST/ ALT/ ALP ≤ 3 times upper normal limit, Total bilirubin ≤2.0mg/dL (In case of
                  liver metastasis AST/ ALT/ ALP ≤ 5 times upper normal limit, in case of bone
                  metastasis, ALP ≤ 5 times upper normal limit)

         11. Patients must have a life expectancy ≥ 12 weeks

        Exclusion Criteria:

          1. Patients who were previously treated with any of the drugs targeting T790M mutation
             such as AZD9291 (Osimertinib), HM61713 (Olmutinib), and CO-1686 (Rociletinib)

          2. Patients currently receiving medications known to be potent inhibitors of CYP3A4 and
             potent inducers of CYP3A4 (at least 1week prior study enrolment)

          3. Patients who have preexisting or coexisting malignancies in other parts except for
             effectively treated non-melanoma skin cancer, CIS cervical cancer, DCIS breast cancer,
             thyroid cancer or malignancies that were effectively treated, have maintained at least
             3 years of remission state and can be regarded as completely cured

          4. Patients who have severe or unstable medical conditions such as prior or current
             clinically significant cardiovascular abnormality in accordance with the
             investigator's judgment such as uncontrolled hypertension, heart failure (NYHA
             classification ≥3), unstable angina or uncontrolled arrhythmia, and acute myocardial
             infarction within 6 months before study enrolment corrected QTcB >450msec in 12 lead
             EKG

          5. Patients with current or prior interstitial lung disease

          6. Patients with current or prior uncontrolled gastrointestinal diseases (e.g., crohn's
             disease, ulcerative colitis, chronic diarrhea, malabsorption) that would preclude
             adequate absorption of IP.

          7. Patients with active hepatitis B (identified by the presence of HBsAg and/or HBV DNA),
             active hepatitis C (identified by the presence of HCV RNA), and known human
             immunodeficiency virus (HIV)

          8. Patients with histories of hypersensitivity to IP or any components of the agent

          9. Patients with any of the following genetic predispositions including galactose
             intolerance, lactose intolerance, or glucose-galactose malabsorption

         10. Patients with symptomatic CNS metastases who are neurologically unstable (Cases with
             radiologically and neurologically stable disease after discontinuation of the
             administration of corticosteroids and anticonvulsants for at least 4 weeks are
             excluded)

         11. Patients with uncontrolled infective diseases (Patients who require non-oral
             antibiotics injection must be excluded, but they can be included if the diseases are
             completely resolved.)

         12. Patients who are difficult or unlikely to comply with study procedures, restrictions,
             requirements, and follow-up managements according to the investigator's judgment

         13. Patients who were administered other study drugs within 30 days before starting the
             study treatment (Patients are permitted if they were given any of the drugs including
             gefitinib, erlotinib, and afatinib)

         14. Patients with 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.

         15. 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:ORR
Time Frame:through study completion (2 years)
Safety Issue:
Description:Objective response rate (ORR) including rate of CR and PR on based of RECIST 1.1

Secondary Outcome Measures

Measure:DCR
Time Frame:through study completion (2 years)
Safety Issue:
Description:Disease control rate (DCR) including rate of CR, PR and SD on based of RECIST 1.1
Measure:PFS
Time Frame:through study completion (2 years)
Safety Issue:
Description:Progression-free survival (PFS) the time from first dose of the study drug until the date of disease progression or death by any cause.
Measure:T790M postive rate in Plasma cell free DNA
Time Frame:through study completion (2 years)
Safety Issue:
Description:
Measure:T790M postive rate in BALF free DNA
Time Frame:through study completion (2 years)
Safety Issue:
Description:
Measure:T790M postive rate in tissue
Time Frame:through study completion (2 years)
Safety Issue:
Description:
Measure:Concordance rate of T790M positivity between plasma & BALF
Time Frame:through study completion (2 years)
Safety Issue:
Description:
Measure:T790M sensitivity & specificity in Plasma & BALF (gold standard: tissue biopsy)
Time Frame:through study completion (2 years)
Safety Issue:
Description:
Measure:The frequency of occurrence of grade 3 or higher AE/SAEs
Time Frame:through study completion (2 years)
Safety Issue:
Description:AE/SAE assessement on the base of NCI-CTCAE (version 4.03).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Asan Medical Center

Trial Keywords

  • T790 mutation
  • Liquid biopsy

Last Updated

January 3, 2018