A Study Osimertinib in Patients With Stage 4 Non-small Cell Lung Cancer With Uncommon EGFR Mutations
Condition: Non Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: osimertinib
Intervention description: 80 mg oral administration daily
Intervention MeSH terms: Osimertinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: EGFR Mutation; osimertinib; exon 18 G719X; exon 20 S7681; exon 21 L861Q

Summary:

      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.
    

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