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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03434418
Recruitment Status : Recruiting
First Posted : February 15, 2018
Last Update Posted : October 10, 2019
Sponsor:
Information provided by (Responsible Party):
Duke University

Tracking Information
First Submitted Date  ICMJE February 9, 2018
First Posted Date  ICMJE February 15, 2018
Last Update Posted Date October 10, 2019
Actual Study Start Date  ICMJE June 30, 2018
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 14, 2018)
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 ]
RECIST 1.1 will be used to measure confirmed partial or complete responses to the study drug.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 14, 2018)
  • 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 ]
    Progression will be defined as time from starting study therapy to disease progression or death (whichever occurs first)
  • AEs as measured by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 [ Time Frame: Up to 3 years ]
    Evaluation of safety using the National Cancer Institute (NCI) CTCAE version 4.03
  • Overall survival as noted by follow-up via composite of telephone or medical record review. [ Time Frame: Up to 5 years ]
    Overall survival as defined as time from starting study therapy until death from any causes.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Osimertinib in Patients With Stage 4 Non-small Cell Lung Cancer With Uncommon EGFR Mutations
Official Title  ICMJE A Single Arm Phase II Study Osimertinib in Patients With Stage 4 Non-small Cell Lung Cancer With Uncommon EGFR Mutations
Brief 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non Small Cell Lung Cancer
Intervention  ICMJE Drug: osimertinib
80 mg oral administration daily
Other Name: Tagrisso
Study Arms  ICMJE Experimental: osimertinib
Intervention: Drug: osimertinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 14, 2018)
37
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2023
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ellen Parker 919-681-4768 Ellen.s.parker@duke.edu
Contact: Debra Shoemaker 919-687-4768 Debra.shoemaker@duke.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03434418
Other Study ID Numbers  ICMJE Pro00088376
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Duke University
Study Sponsor  ICMJE Duke University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Thomas Stinchcombe, MD Duke University
PRS Account Duke University
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP