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

• ClinicalTrials.gov Identifier: NCT03434418
• Recruitment Status: Recruiting
• First Posted: February 15, 2018
• Last Update Posted: October 10, 2019
• Sponsor: Duke University
• Information provided by (Responsible Party): Duke University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Non Small Cell Lung Cancer	Drug: osimertinib	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single Arm Phase II Study Osimertinib in Patients With Stage 4 Non-small Cell Lung Cancer With Uncommon EGFR Mutations
• Actual Study Start Date: June 30, 2018
• Estimated Primary Completion Date: June 30, 2021
• Estimated Study Completion Date: June 30, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: osimertinib	Drug: osimertinib; 80 mg oral administration daily; Other Name: Tagrisso

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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)
2. 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
3. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Ellen Parker; 919-681-4768; Ellen.s.parker@duke.edu

Contact: Debra Shoemaker; 919-687-4768; Debra.shoemaker@duke.edu

Locations

United States, North Carolina

Duke University Medical Center; Recruiting

Durham, North Carolina, United States, 27710

Contact: Ellen Parker 919-681-3510 Ellen.s.Parker@duke.edu

Contact: Debra Shoemaker 919-681-4768 Debra.shoemaker@duke.edu

Principal Investigator: Thomas Stinchcombe, MD

United States, Ohio

The Ohio State University Medical Center; Recruiting

Columbus, Ohio, United States, 43202

Contact: April Green 614-685-7037 April.Green2@osumc.edu

Contact: Stephanie Hehemann-Smith 613-366-6413 stephanie.hehemann-smith@osumc.edu

Principal Investigator: Greg Otterson, MD

United States, Pennsylvania

University of Pittsburgh Medical Center; Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contact: Daniel Goldstein 412-864-7820 goldsteindj@upmc.edu

Contact: Jennifer Ruth 412-623-8963 ruthj2@upmc.edu

Principal Investigator: Liza Villaruz, MD

Sponsors and Collaborators

Duke University

Investigators

• Principal Investigator: Thomas Stinchcombe, MD; Duke University

More Information

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT03434418
• Other Study ID Numbers: Pro00088376
• First Posted: February 15, 2018
• Last Update Posted: October 10, 2019
• Last Verified: September 2019

• 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

Keywords provided by Duke University:

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

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Osimertinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action