A Phase 2 Study of Osimertinib in Combination With Selumetinib in EGFR Inhibitor naïve Advanced EGFR Mutant Lung Cancer

NCT03392246 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 17-540
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 4

Brief Summary

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

• Osimertinib (Tagrisso)
• Selumetinib

Conditions

Non-small Cell Lung Cancer

Keywords

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Best Objective Response

  RECIST1.1 measurements of CT scans will be measured during treatment to determine the objective response rate for patients being treated with combination osimertinib and selumetinib. A response rate and a 95% confidence interval will be calculated.

  2 years

Secondary Outcomes (4)

• Progression Free Survival

  2 years

• Overall Survival

  2 years

• Tolerability Proportion

  2 years

• Toxicity Grading

  2 years

Study Arms (1)

Osimertinib + Selumetinib

EXPERIMENTAL

* Selumetinib are to be administered orally intermittently (4 days on, 3 days off) * Osimertinib are to be administered orally on a daily basis

Drug: Osimertinib; Drug: Selumetinib

Interventions

Osimertinib DRUG

may stop (or "inhibit") the growth of a cancer with a mutation in the EGFR gene

Also known as: Tagrisso, AZD9291

Osimertinib + Selumetinib

Selumetinib DRUG

may enhance the effect of osimertinib to stop (or "inhibit") the growth of a cancer with a mutation in the EGFR gene

Also known as: AZD6244

Osimertinib + Selumetinib

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 (see 3.1.3 and 3.2.1).
• 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 for metastatic disease. Patients who have completed adjuvant or neo-adjuvant chemotherapy \> 6 months ago are considered treatment naïve
• 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 Cockcrft-Gault formula.
• Participants should have biopsy tissue (or a cell block from a malignant effusion) at time of diagnosis available for targeted next-generation sequencing. The testing does not have to be completed prior to study enrollment. Biopsy can be performed at an outside institution as long as sufficient tissue is available.

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 advanced NSCLC
• Prior radiotherapy \</= 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 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 or selumetinib.
• Patients currently receiving and unable to stop using medications 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.
• Patients currently receiving and unable to stop high doses of supplemental vitamin E. Selumetinib capsules contain vitamin E and high doses of vitamin E have been reported to cause bleeding and interfere with blood coagulation processes.
• 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 and cancer of the cervix in situ.
• 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; previous moderate or severe impairment of left ventricular systolic function (LVEF \<45% on echocardiography or equivalent on MUGA) even if full recovery has occurred; prior or current severe valvular heart disease; prior or current cardiomyopathy including but not limited to the following:
• Known hypertrophic cardiomyopathy
• Known arrhythmogenic right ventricular cardiomyopathy

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• National Comprehensive Cancer Network: collaborator

Study Sites (4)

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib; AZD 6244

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 Janne, 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: January 2, 2018
• First Posted: January 5, 2018
• Study Start: January 31, 2018
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)