Osimertinib In EGFR Mutant Lung Cancer

NCT03586453 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 18-070
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is studying a targeted therapy as a possible treatment for Non-Small Cell Lung Cancer (NSCLC) with an EGFR mutation. The names of the study drug involved in this study is: \- Osimertinib (Tagrisso)

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Non-Small Cell Lung Cancer (NSCLC); Epidermal Growth Factor Receptor (EGFR) mutation

Outcome Measures

Primary Outcomes (1)

• Mechanisms of resistance to Osimertinib

  Evaluated by comparing the genomic changes using targeted next generation sequencing in the post-osimertinib tumor to the pre-treatment tumor specimen.

  4 Months

Secondary Outcomes (4)

• Best objective response

  6 months

• Overall Response Rate

  3 years

• Progression-free survival (PFS)

  2 years

• Overall survival

  2 years

Study Arms (1)

Osimertinib

EXPERIMENTAL

Osimertinib: Oral, once a day, dosage determined per protocol

Drug: Osimertinib

Interventions

Osimertinib DRUG

Patients who fulfill eligibility criteria will be entered into the trial to receive Osimertinib. After the screening procedures confirm participation in the research study: * Osimertinib: Oral, Daily 28 day cycle. * Radiographic assessment: every 2 cycles for first 6 months and then every 3 cycles until disease progression. * Tumor biopsy between C4 and C8 and at disease progression

Also known as: Tagrisso, AZD9291

Osimertinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically confirmed stage IV NSCLC (per AJCC 7th edition) with either the L858R or exon 19 deletion activating EGFR mutation as identified in a CLIA-approved laboratory from tumor tissue.
• Note: recurrent stage IV disease initially diagnosed at an earlier stage is considered eligible, provided prior treatment criteria is met.
• Participants must have measurable disease at baseline, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam.
• Participants must be aged ≥ 18 years
• Participants must have an ECOG performance status of 0-1 (Appendix A)
• Participants must have normal organ and marrow function as defined below:
• absolute neutrophil count ≥1,500/mcL
• platelets ≥100,000/mcL
• hemoglobin \>9.0 g/dL
• total bilirubin \< 1.5 times the ULN if no liver metastases or \< 3 times the ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases
• AST(SGOT)/ALT(SGPT) \<2.5 × institutional upper limit of normal or \<5 times the ULN in the presence of liver metastases
• creatinine ≤ 1.5 x institutional upper limit of normal
• \--- OR
• creatinine clearance ≥50 mL/min as determined by the Cockcroft-Gault formula.
• Note: For participants entering study after starting commercial osimertinib, elevations in hepatic transaminases (AST/ALT) and/or total bilirubin \< grade 2 at study entry are acceptable (see protocol Table 2).

You may not qualify if:

• Prior or ongoing treatment with any of the following:
• EGFR targeted therapy (TKI or antibody) or any other targeted therapies targeting the ERBB family except for subjects receiving first line osimertinib during the first three months of therapy.
• Any cytotoxic chemotherapy, investigational agents, immunotherapy or anticancer drugs for the treatment of metastatic NSCLC
• Note: Patients who have completed adjuvant or neo-adjuvant chemotherapy \> 6 months ago are considered treatment naïve
• Prior radiotherapy, including CNS radiation, within 2 weeks of the first dose of study treatment.
• Uncontrolled central nervous system (CNS) disease, including parenchymal brain metastases, leptomeningeal disease, or spinal cord compression. Patients with asymptomatic untreated brain metastases are eligible. Patients with treated CNS disease will be allowed to enroll provided they have asymptomatic clinically confirmed stable disease with ≥2 weeks since definitive CNS therapy (radiation or surgery) and ≥2 weeks without systemic steroids. Patients may undergo either whole brain radiation or stereotactic radiosurgery prior to study entry.
• History of allergic reactions attributed to compounds, or any of its excipients, of similar chemical or biologic composition to osimertinib.
• Patients currently receiving and unable to stop using medications or herbal supplements known to be potent inhibitors or inducers of CYP3A4. The full list of medications that would make a patient ineligible are provided in Appendix B, along with indicated washout times.
• Any unresolved toxicities from prior therapy, including commercial osimertinib, greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment.
• Malignancies within the past 3 years excluding adequately treated basal or squamous cell carcinomas of the skin without local or distant metastases.
• Refractory nausea and vomiting, chronic gastrointestinal diseases, previous significant bowel resection, or any process that compromises the ability to swallow or absorb oral medication
• Significant medical history or unstable medical comorbidities, including:
• heart disease including congestive heart failure (NYHA Grade II or greater); unstable angina; prior myocardial infarction (NSTEMI or STEMI) within 6 months prior to study enrollment; hypertension with a systolic blood pressure of \>150 mm Hg or diastolic blood pressure of \>100 mm Hg while on antihypertensive medication
• any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, e.g. complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval \>250msec, have normal QT interval on ECG evaluation QT corrected Fridericia (QTcF) of ≤ 450 ms in males or ≤ 470 ms in females
• any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives, or any concomitant medication known to the prolong the QT interval and cause Torsades de Pointes and listed in Appendix B that a patient is unable to stop

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• AstraZeneca: collaborator

Study Sites (2)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Pasi A Jänne, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 2, 2018
• First Posted: July 13, 2018
• Study Start: August 13, 2018
• Primary Completion (Estimated): February 28, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)