Clinical Trials /

A Study Osimertinib in Patients With Stage 4 Non-small Cell Lung Cancer With Uncommon EGFR Mutations

NCT03434418

Description:

This is a research study to find out if a drug called, osimertinib, is safe and effective in treating advanced Non-Small Cell Lung Cancer (NSCLC) by targeting the treatment of epidermal growth factor receptor (EGFR) mutation exon 18 G719X, exon 20 S7681, or exon 21 L861Q. Patients on the study will not have had previous tyrosine kinase inhibitor (TKI) treatment.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study Osimertinib in Patients With Stage 4 Non-small Cell Lung Cancer With Uncommon EGFR Mutations
  • Official Title: A Single Arm Phase II Study Osimertinib in Patients With Stage 4 Non-small Cell Lung Cancer With Uncommon EGFR Mutations

Clinical Trial IDs

  • ORG STUDY ID: Pro00088376
  • NCT ID: NCT03434418

Conditions

  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
osimertinibTagrissoosimertinib

Purpose

This is a research study to find out if a drug called, osimertinib, is safe and effective in treating advanced Non-Small Cell Lung Cancer (NSCLC) by targeting the treatment of epidermal growth factor receptor (EGFR) mutation exon 18 G719X, exon 20 S7681, or exon 21 L861Q. Patients on the study will not have had previous tyrosine kinase inhibitor (TKI) treatment.

Detailed Description

      This is a research study to find out if a drug called, osimertinib, is safe and effective in
      treating advanced Non-Small Cell Lung Cancer (NSCLC) by targeting the treatment of epidermal
      growth factor receptor (EGFR) mutation exon 18 G719X, exon 20 S7681, or exon 21 L861Q.
      Patients on the study will not have had previous tyrosine kinase inhibitor (TKI) treatment.

      Patients who have one of the following EGRF mutations: exon 18 G719X, exon 20 S7681, or exon
      21 L861Q) may be eligible to participate in this study. If enrolled into the study, the study
      team will give the patient a supply of the study drug, osimbertinib (80 mg) to take at home.
      The patient will be asked to take the study drug by mouth on days 1-28 of each study cycle.
      As part of this study, the patient will have blood samples other tests, exams and procedures
      done for study purposes and their standard of care. Patient participation in the study will
      last for up to 2 years after completion of the last dose of the study drug or until your
      condition worsens or intolerable adverse events as deemed by the study doctor.

      There are possible patient risks to this study that include but are not limited to diarrhea,
      changes to the lining of the mouth (e.g. ulcers), rash, dry skin, itching, and nail
      infections.
    

Trial Arms

NameTypeDescriptionInterventions
osimertinibExperimental
  • osimertinib

Eligibility Criteria

        Inclusion Criteria:

          -  EGFR mutations as performed on a CLIA certified laboratory demonstrating EGFR exon 18
             G719X, exon 20 S768I, or exon 21 L861Q. Patients with compound (also referred to as
             multiple mutations) will be eligible provided the NSCLC demonstrates one of these
             mutations).

          -  Histological or cytological confirmation diagnosis of Stage 4 NSCLC.

          -  Measurable disease by RECIST 1.1 (please refer to appendix 4)

          -  The following laboratory values obtained ≤ 14 days prior to study initiation.

          -  Hematology: ANC ≥ 1, 500 / ml, platelet count, ≥ 100,000 / ml, hemoglobin ≥ 9.0 g / dl

          -  Hepatic:ALT or ALT < 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

          -  Renal: Cockcroft-Gault calculated creatinine clearance of ≥ 45 ml/min or creatinine
             ≤1.5 x ULN

          -  Have normal QT interval on ECG evaluation QT corrected of ≤ 450 ms in males or ≤ 470
             ms in females obtained from 3 electrocardiograms (ECGs), using the screening clinic
             ECG machine-derived QTc value

          -  Cardiac ejection fraction of ≥ 45%

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or1

          -  Negative pregnancy test done ≤7 days (or per institutional policy) prior to treatment,
             for women of childbearing potential only. Female must use highly effective
             contraceptive measures, and must have a negative pregnancy test 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 considered 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 sterilization by hysterectomy, bilateral
             oophorectomy or bilateral salpingectomy but not tubal ligation

          -  Male subjects must be willing to use barrier contraception

          -  Age ≥ 18 years

          -  Provision of written informed consent prior to any study-specific procedures

        Exclusion Criteria:

          -  Prior therapy with EGFR TKI therapy

          -  Greater than 2 lines of prior systemic therapy for metastatic non-small cell lung
             cancer.

          -  Any cytotoxic chemotherapy or other anticancer drugs from previous treatment regimen
             or clinical study within 14 days of first dose of study drug.

          -  Treatment with an investigational drug within 5 half-lives of the compound

          -  Other active malignancy ≤ 2 years prior to registration. EXCEPTIONS: Non-melanotic
             skin cancer or carcinoma-in-situ of the cervix. NOTE: If there is a history of prior
             malignancy, patients must not be receiving other specific treatment (i.e. hormonal
             therapy) for their cancer

          -  Prior radiotherapy ≤ 14 days

          -  Untreated symptomatic brain metastases (treated brain metastases are allowed provided
             > 14 days have elapsed from completion of radiotherapy and patient is neurologically
             stable as assessed by treating physician).

          -  Malabsorption syndrome, 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

          -  Detection of concurrent EGFR mutation with exon 20 T790M, exon 19 deletion, exon 21
             L858R mutation or exon 20 insertion. Patients with compound (also referred to as
             multiple mutations) will be excluded if the molecular testing includes one of these
             mutations.

          -  Active pregnancy or breast-feeding: Pregnant women are excluded from this study
             because the effects of osimertinib on the development of the fetus are unknown, and
             there is potential for teratogenic or abortifacient effects. Because there is an
             unknown but potential risk for adverse events in nursing infants secondary to
             treatment of the mother with osimertinib, breastfeeding should be discontinued if the
             mother is treated with these agents.

          -  Grade ≥ 2 blurred vision, conjunctivitis, corneal ulcer, dry eye, or keratitis
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate as assessed by the investigator using Response Evaluation Criteria In Solid Tumors RECIST 1.1 (brand name)
Time Frame:Up to 3 years
Safety Issue:
Description:RECIST 1.1 will be used to measure confirmed partial or complete responses to the study drug.

Secondary Outcome Measures

Measure:Progression free survival as measured by Response Evaluation Criteria In Solid Tumors RECIST 1.1 (brand name) as assessed by the investigator.
Time Frame:Up to 5 years
Safety Issue:
Description:Progression will be defined as time from starting study therapy to disease progression or death (whichever occurs first)
Measure:AEs as measured by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
Time Frame:Up to 3 years
Safety Issue:
Description:Evaluation of safety using the National Cancer Institute (NCI) CTCAE version 4.03
Measure:Overall survival as noted by follow-up via composite of telephone or medical record review.
Time Frame:Up to 5 years
Safety Issue:
Description:Overall survival as defined as time from starting study therapy until death from any causes.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Duke University

Trial Keywords

  • EGFR Mutation
  • osimertinib
  • exon 18 G719X
  • exon 20 S7681
  • exon 21 L861Q

Last Updated