Clinical Trials /

Olmutinib Trial in T790M (+) NSCLC Patients Detected by Liquid Biopsy Using BALF Extracellular Vesicular DNA

NCT03228277

Description:

The purpose of this study is to evaluate the efficacy of Olmutinib(Olita®) in patients with T790M-positive non-small cell lung cancer (NSCLC) confirmed using DNA extracted from extracellular vesicles of bronchoalveolar lavage fluid.

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

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Olmutinib Trial in T790M (+) NSCLC Patients Detected by Liquid Biopsy Using BALF Extracellular Vesicular DNA
  • Official Title: Phase II, Multicenter, Single-arm, Open-label Study to Evaluate the Efficacy of Olmutinib(Olita®) in Patients With NSCLC Who Harboring T790M Mutation Confirmed Using DNA Extracted From Extracellular Vesicles in Bronchoalveolar Lavage Fluid

Clinical Trial IDs

  • ORG STUDY ID: KASTT005_BAL_Olita
  • NCT ID: NCT03228277

Conditions

  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
OlmutinibOlita®Olmutinib

Purpose

The purpose of this study is to evaluate the efficacy of Olmutinib(Olita®) in patients with T790M-positive non-small cell lung cancer (NSCLC) confirmed using DNA extracted from extracellular vesicles of bronchoalveolar lavage fluid.

Detailed Description

      This is a single-arm, open-label, Phase 2 study to assess the anti-tumor efficacy of
      Olmutinib(Olita®) administered to patients with T790M-positive NSCLC confirmed using DNA
      extracted from extracellular vesicles in bronchoalveolar lavage fluid as measured by
      objective response rate (ORR).
    

Trial Arms

NameTypeDescriptionInterventions
OlmutinibExperimentalSingle arm of Olmutinib, staring dose of 800 mg
  • Olmutinib

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female, aged at least 19 years

          2. Obtained written informed consent

          3. Histologically- or cytologically confirmed diagnosis of unresectable Stage IIIB or IV
             non-small cell lung cancer.

          4. Confirmation that the tumor harbours an EGFR mutation known to be associated with EGFR
             TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q).

          5. Eastern Cooperative Oncology Group performance status of 0 to 2

          6. Prior treatment with at least one line of a single agent EGFR TKI (gefitinib,
             erlotinib, afatinib) and confirmed progressive disease after treatment with EGFR TKI

               -  Regardless of treatment sequence between previous chemotherapy and EGFR TKI

               -  Regardless of whether they were administered conventional chemotherapy, if
                  therapy were treated with at least one EGFR TKI

          7. Subjects who will undergo bronchoscopy/ BAL procedures and sufficient amount of BAL
             fluid is carefully collected for EGFR mutation analysis.

          8. Confirmation that the extracellular vesicles (EV) extracted from bronchoalveolar
             lavage fluid (BALF) harbour T790M mutation (It can be replaced previous the same
             result throughout the follow up period before enrollment.)

          9. At least one measurable disease (except brain) at baseline according to RECIST version
             1.1

         10. Female subjects must be postmenopausal (for at least one year), or, if sexually
             active, be practicing an effective method of birth control (e.g., prescription oral
             contraceptives, contraceptive injections, intrauterine device, double-barrier method,
             contraceptive patch, male partner sterilization) before entry and throughout the
             study; and, for those of childbearing potential, have a negative urinary β-hCG
             pregnancy test at screening.

         11. Male subjects should be willing to use barrier methods which are suitable for sexual
             partner throughout the study.

         12. Subjects must have signed an informed consent document indicating that they understand
             the purpose of and procedures required for the study and are willing to participate in
             the study. The subject also must sign and date the consent form before specific
             procedures or sampling.

         13. Adequate organ function as defined by liver, kidney, and hematologic laboratory
             testing as below

               -  Absolute neutrophil count (ANC) ≥ 1500/mm3, Platelet ≥ 100,000 /mm3 Hemoglobin
                  (Hb) ≥ 9.0g/dL

               -  Serum creatinine ≤ upper limit of normal (ULN)

               -  AST/ALT/ALP ≤ 3 times ULN, Total bilirubin ≤2.0 mg/dL AST/ALT/ALP ≤ 5 times ULN
                  in patients with metastatic lesions to the liver ALP ≤ 5 times ULN in patients
                  with metastatic lesions to the bone

         14. Expected survival of at least 12 weeks

        Exclusion Criteria:

          1. Previous treatment with anticancer therapies, EGFR-TKI, olmutinib (HM61713), or other
             drugs that target T790M-positive mutant EGFR with sparing of wild-type, Osimertinib
             (AZD9291), Rociletinib (CO-1686), investigational agent(s) within 30 days prior to the
             first administration of study drug, radiotherapy

          2. Treatment with a potent cytochrome P450 (CYP) 3A4 inhibitors or inducers

          3. History of any other malignancy EXCEPTIONS are:

               -  adequately treated non-melanoma skin cancer, curatively treated in situ cancer of
                  the cervix, ductal carcinoma in situ (DCIS) of the breast, thyroid cancer

               -  other malignancies diagnosed prior to randomisation and treated with no evidence
                  of disease recurrence more than 3 years

          4. Any history or presence of clinically relevant cardiovascular abnormalities such as
             uncontrolled hypertension, congestive heart failure NYHA classification of III or IV,
             unstable angina or poorly controlled arrhythmia as determined by the investigator.
             Myocardial infarction within 6 months prior to enrolment. Increased QTc interval > 450
             ms on screening ECG

          5. Any history of presence of interstitial lung disease

          6. Any history or presence of poorly controlled gastrointestinal disorders that could
             affect the absorption of the trial drug (e.g. Crohn's disease, ulcerative colitis,
             chronic diarrhea, malabsorption).

          7. Ongoing active infection with, hepatitis B virus (infection defined as a positive
             HbsAg and/ or HBV DNA), hepatitis C virus (infection defined as a positive HCV RNA),
             or human immunodeficiency virus (HIV) Type 1/2 infection at the time of screening.

          8. Known history of hypersensitivity to active or inactive excipients of study drug
             (olmutinib) or drugs with a similar chemical structure of olmutinib

          9. Subjects with galactose intolerance, Lapp lactase deficiency or glucose-galactose
             malabsorption

         10. Symptomatic or uncontrolled central nervous system (CNS) metastases (Patients are
             eligible if they have completed their treatment and have recovered from the acute
             effects of radiation therapy or surgery prior to the start of study medication, have
             discontinued corticosteroid treatment for these metastases for at least 4 weeks and
             are neurologically and radiologically stable)

         11. Uncontrolled active infectious disease (with the exception of those that are
             considered to be needed topical antibiotics, however subjects can be enrolled into the
             study after they complete their treatment)

         12. Unable to attend all the study visits or comply with study procedures

         13. Patients who had received other investigational product within 30 days prior to the
             first administration of study drug except for gefitinib, erlotinib, or afatinib
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Change from baseline at every 6 weeks until disease progression or withdrawal from study, assessed up to 12 months
Safety Issue:
Description:defined as the proportion of patients who achieved complete remission(CR) or partial remission(PR) based on RECIST version 1.1

Secondary Outcome Measures

Measure:Disease control rate (DCR)
Time Frame:Change from baseline at every 6 weeks until disease progression or withdrawal from study, assessed up to 12 months
Safety Issue:
Description:defined as the proportion of patients with a documented CR, PR, and SD during the treatment cycles according to the RECIST version 1.1
Measure:Progression-free survival (PFS)
Time Frame:Change from baseline at every 6 weeks until disease progression or withdrawal from study, assessed up to 12 months
Safety Issue:
Description:defined as the time from first administration of study drug to determination of tumor progression by RECIST version 1.1 or death due to any cause, whichever occurs first

Details

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

Trial Keywords

  • Extracellular vesicles
  • Bronchoalveolar lavage fluid
  • Liquid biopsy
  • T790M
  • NSCLC
  • Exosomes
  • EGFR mutation testing

Last Updated

July 20, 2017