Osimertinib and Gefitinib in EGFR Inhibitor naïve Advanced EGFR Mutant Lung Cancer

NCT03122717 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 16-627
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is studying a combination of two drugs as a possible treatment for Non-Small Cell Lung Cancer (NSCLC) with an EGFR mutation. The interventions involved in this study are:

• Osimertinib (Tagrisso)
• Gefitinib (Iressa)

Conditions

Non-Small Cell Lung Cancer

Keywords

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Number of patients completing combination therapy with gefitinib and osimertinib for 6 x 28 day cycles

  The feasibility of combination gefitinib/osimertinib dosing will be determined through evaluation of the number of patients in each cohort who are able to remain on combination therapy for 6 x 28 day cycles.

  3 years

Secondary Outcomes (4)

• Rate of treatment-related Grade 3-5 adverse events

  3 years

• Objective response rate

  3 years (each cycle is 28 days)

• Progression free survival

  3 years

• Overall Survival

  3 years

Study Arms (1)

Gefitinib + Osimertinib

EXPERIMENTAL

* Gerfitinib will administered orally at a pre determine dose daily * Osimertinib will administered orally at a pre determine dose daily

Drug: Gefitinib; Drug: Osimertinib

Interventions

Gefitinib DRUG

gefitinib is a EGFR inhibitor

Also known as: Iressa

Gefitinib + Osimertinib

Osimertinib DRUG

An orally available, irreversible, third-generation, mutant-selective epidermal growth factor receptor (EGFR) inhibitor

Also known as: Tagrisso

Gefitinib + 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. 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, 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 can have no prior history of any EGFR-directed therapy, including TKIs or antibodies, and must also be chemotherapy and immunotherapy naïve. Patients who have completed adjuvant or neo-adjuvant chemotherapy or immunotherapy \>6 months ago are considered treatment naive.
• Participants must be aged ≥ 18 years
• Participants must have an ECOG performance status of 0-1 (Appendix A)
• Participants must have a life expectancy of greater than 12 weeks
• Participants must have normal organ and marrow function as defined below:
• leukocytes ≥3,000/mcL
• 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 within normal institutional limits OR
• creatinine clearance ≥50 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.

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
• Any cytotoxic chemotherapy, investigational agents, or anticancer drugs for the treatment of metastatic NSCLC
• Prior radiotherapy within 2 weeks of the first dose of study treatment. Patients who have received radiation to more than 25% of the bone marrow are not eligible at any time.
• No 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 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 of similar chemical or biologic composition to gefitinib or osimertinib.
• Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inhibitors of CYP3A4 (Appendix B). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4. The full list of medications that would make a patient ineligible are provided in Appendix B.
• Any unresolved toxicities from prior therapy 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, mean resting corrected QT value (QTc) of \>470msec
• 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
• past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease

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

Gefitinib; osimertinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Pasi Janne, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prinicipal Investigator

Study Record Dates

• First Submitted: April 4, 2017
• First Posted: April 21, 2017
• Study Start: May 9, 2017
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)