- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03434418
A Study Osimertinib in Patients With Stage 4 Non-small Cell Lung Cancer With Uncommon EGFR Mutations
A Single Arm Phase II Study Osimertinib in Patients With Stage 4 Non-small Cell Lung Cancer With Uncommon EGFR Mutations
Study Overview
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
North Carolina
-
Durham, North Carolina, United States, 27710
- Duke University Medical Center
-
-
Ohio
-
Columbus, Ohio, United States, 43202
- The Ohio State University Medical Center
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, United States, 15232
- University of Pittsburgh Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: osimertinib
|
80 mg oral administration daily
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate as Assessed by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Time Frame: Up to 4 years
|
The number of participants who have a partial response or complete response to the study drug.
Complete response (CR) = Disappearance of all target lesions and reduction in the short axis measurement of all pathologic lymph nodes to ≤10 mm; partial response (PR) = ≥30% decrease in the sum of the longest diameter of the target lesions compared with baseline.
|
Up to 4 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression Free Survival (PFS) as Measured by Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Time Frame: Up to 4 years
|
Progression will be defined as time from starting study therapy to disease progression or death (whichever occurs first).
|
Up to 4 years
|
Number of Participants With Adverse Events (AEs) as Measured by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03
Time Frame: Up to 4 years
|
Adverse events (regardless of attribution) observed in all enrolled participants, except for those withdrawn prior to study treatment or fail to receive study treatment for various reasons.
Counts and percentages of participants who experienced any AEs are calculated.
|
Up to 4 years
|
Overall Survival as Noted by Follow-up Via Composite of Telephone or Medical Record Review.
Time Frame: Up to 4 years
|
Overall survival as defined as time from starting study therapy until death from any causes.
|
Up to 4 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Thomas Stinchcombe, MD, Duke University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Osimertinib
Other Study ID Numbers
- Pro00088376
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Non Small Cell Lung Cancer
-
AIO-Studien-gGmbHBristol-Myers Squibb; Eli Lilly and Company; Merck Sharp & Dohme LLC; Pfizer; Gilead... and other collaboratorsRecruitingSmall-cell Lung Cancer | Non-small Cell Lung Cancer Metastatic | Non-small Cell Lung Cancer Stage I | Metastatic Non-small Cell Lung Cancer (NSCLC) | Non Small Cell Lung Cancer Stage III | Non-small Cell Lung Cancer Stage IIGermany
-
WindMIL TherapeuticsBristol-Myers SquibbTerminatedNSCLC | Lung Cancer | Lung Cancer Metastatic | Lung Cancer, Non-small Cell | Non Small Cell Lung Cancer | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Metastatic | Non Small Cell Lung Cancer MetastaticUnited States
-
University of California, San FranciscoAstraZenecaActive, not recruitingStage IIIA Non-Small Cell Lung Cancer | Stage I Non-Small Cell Lung Cancer | Stage IA Non-Small Cell Lung Cancer | Stage IB Non-Small Cell Lung Cancer | Stage II Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Cancer | Stage IIB Non-Small Cell Lung CancerUnited States
-
Alexander ChiNot yet recruitingNon-small Cell Lung Cancer Stage III | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Stage I | Non-small Cell Carcinoma | Non-small Cell Lung Cancer Stage IIChina
-
University of Wisconsin, MadisonNational Cancer Institute (NCI)CompletedStage IIIA Non-small Cell Lung Cancer | Stage IIIB Non-small Cell Lung Cancer | Extensive Stage Small Cell Lung Cancer | Recurrent Small Cell Lung Cancer | Recurrent Non-small Cell Lung Cancer | Stage IV Non-small Cell Lung Cancer | Healthy, no Evidence of Disease | Limited Stage Small Cell Lung... and other conditionsUnited States
-
National Cancer Institute (NCI)Not yet recruitingStage IIIA Non-small Cell Lung Cancer | Stage IA Non-small Cell Lung Cancer | Stage IB Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB Non-small Cell Lung CancerCanada
-
National Cancer Institute (NCI)TerminatedStage IIIA Non-small Cell Lung Cancer | Stage IA Non-small Cell Lung Cancer | Stage IB Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB Non-small Cell Lung CancerUnited States
-
Karen KellyBristol-Myers Squibb; National Cancer Institute (NCI); TransgeneCompletedStage IIIA Non-Small Cell Lung Cancer | Stage IIIB Non-Small Cell Lung Cancer | Recurrent Non-Small Cell Lung Carcinoma | Stage IV Non-Small Cell Lung Cancer | Stage I Non-Small Cell Lung Cancer | Stage II Non-Small Cell Lung CancerUnited States
-
Stanford UniversityAstraZenecaRecruitingNon-small Cell Lung Cancer Stage III | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Stage I | Non-small Cell Lung Cancer Stage IIUnited States
-
Ohio State University Comprehensive Cancer CenterActive, not recruitingStage IIIA Non-small Cell Lung Cancer | Stage IIIB Non-small Cell Lung Cancer | Recurrent Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB Non-small Cell Lung CancerUnited States
Clinical Trials on osimertinib
-
Li ZhangHubei Cancer HospitalNot yet recruitingStage IV Non-small Cell Lung CancerChina
-
Qingdao Central HospitalRecruiting
-
AstraZenecaActive, not recruitingNon Small Cell Lung Cancer (Stage III)United States, Spain, Taiwan, Thailand, Vietnam, Turkey, Korea, Republic of, Brazil, Hungary, India, Japan, Mexico, Peru, Russian Federation, China, Malaysia, Argentina
-
Wuhan Union Hospital, ChinaNot yet recruitingNon Small Cell Lung Cancer
-
Vestre Viken Hospital TrustActive, not recruitingLung CancerDenmark, Sweden, Lithuania, Norway
-
Suzhou Genhouse Bio Co., Ltd.RecruitingNon-Small Cell Lung Cancer With EGFR MutationChina
-
AstraZenecaTerminated
-
Istituto Oncologico Veneto IRCCSActive, not recruitingEGF-R Positive Non-Small Cell Lung CancerItaly
-
Shanghai JMT-Bio Inc.CSPC ZhongQi Pharmaceutical Technology Co., Ltd.Not yet recruitingLocally Advanced or Metastatic Non-Small Cell Lung Cancer | EGFR Exon20 Insertion Mutations
-
Qingdao Central HospitalRecruiting