Osimertinib With Stereotactic Radiosurgery (SRS) in Brain Metastases From EGFR Positive NSCLC

Phase 1 Trial of Osimertinib With Stereotactic Radiosurgery (SRS) in Patients With Brain Metastases From EGFR Positive Non-Small-Cell Lung Cancer (NSCLC)

Investigating potential of controlling brain metastases in patients with EGFR positive NSCLC.

Study Overview

• Status: Completed
• Conditions: NSCLC; Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Osimertinib

Detailed Description

In patients with EGFR positive NSCLC with 1-10 brain metastases, we are investigating whether we can control the macro brain metastases with Stereotactic Radiosurgery (SRS) and control the micro metastases with targeted agent Osimertinib and avoid whole brain radiation that could potentially lead to significant cognitive decline.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33176
      • Maimi Cancer Institute - Baptist Health South Florida
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Confirmed pathology of EGFR mutation positive NSCLC with new brain metastases.
• Ability to care for self and ability to walk 50% of waking hours (ECOG Performance Status of 0-2)
• 1-10 brain metastases with intra-cranial brain metastasis must measure 3cm or less in the greatest dimension.
• Hemoglobin ≥9 g/dL, White Blood Count Absolute ≥3.0 x 10^9/L, Granulocyte count ≥1.5 x 10^9/L, and platelet count ≥100 x 10^9/L
• Serum Bilirubin ≤ 1.5 x upper limit of normal (ULN)
• AST and/or ALT ≤ 2 ULN (≤ 5 x ULN when clearly attributable to liver metastases)
• Serum creatinine ≤ 1.5 ULN or calculated creatinine clearance > 60ml/min
• For women of childbearing potential-Negative pregnancy test within one week prior to start of therapy.
• For all sexually active male and female patients of reproductive potential, employ two methods of highly effective and acceptable forms of contraception throughout the study and for 120 days following the final dose of osimertinib.

Exclusion Criteria:

• Patients with leptomeningeal metastases documented by MRI or cerebrospinal fluid (CSF).
• Significant intratumoral or peritumoral hemorrhage
• Brain metastases within 5 mm of the optic chiasm or optic nerve
• Brainstem metastases
• Gastrointestinal disorders with diarrhea as a major symptom
• Clinically significant or uncontrolled cardiac disease (NYHA functional classification of 3 or 4)
• Pre-existing interstitial lung disease or pneumonitis
• Unable to undergo brain MRI
• HIV or Hepatitis B or C
• Prior treatments must be resolved to an asymptomatic state at time of enrollment
• Medical conditions that could cause safety risks
• Currently receiving investigational cancer therapy.
• Mean QT interval corrected heart rate (QTc)≥470ms calculated from 3 EKGs
• Left Ventricular Ejection Fraction (LVEF) ≤ 50%
• Use of strong CYP3A inhibitors
• Use of strong CYP3A4 inducers
• Use of potent CYP2C8 inhibitors
• Hypersensitivity to osimertinib or any of its ingredients
• corneal ulceration
• pregnant or breast-feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Maximum Tolerated Dose of Osimertinib with standard of care; For patients with 1-10 brain metastases, begin daily Osimeritinib 0-7 days prior to stereotactic radiosurgery (SRS), provide daily Osimeritinib concurrently with radiotherapy, followed by maintenance Osimeritinib until disease progression, withdrawal, or unacceptable toxicity. Dose Level 1: 80mg daily. Dose Level -1: 40mg daily

Drug: Osimertinib; Drug: Osimertinib 80mg or 40mg; Other Names: Tagrisso

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD) of Osimertinib with (SRS)	To determine the safety, tolerability and maximum tolerated dose of Osimertinib, when administered in combination with SRS in patients with EGFR positive NSCLC with brain metastases.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with progression free survival	To assess the six-month intra-cranial and extra-cranial progression-free survival (PFS-6) in patients with EGFR positive NSCLC brain metastases treated with Osimertinib and SRS (PFS is defined as the time from clinical registration to intra-or extra-cranial tumor progression or death)	6 months
Length of overall survival	To assess the overall survival (OS) in patients with EGFR positive NSCLC Brain Metastases treated with Osimertinib and SRS	2 years
Difference in outcome vs. standard of care	To compare results of our clinical trial to patients with EGFR positive NSCLC with brain metastases treated with SRS alone (1-10 brain Metastases)	2 years
Intra-cranial and Extra-cranial Overall Response Rate (ORR)	To assess Overall response rate (ORR) both intracranial and extracranial, defined as the proportion of patients with a best overall confirmed response of complete response (CR) or partial response (PR) in the whole body as assessed per RECIST 1.1 by the investigator.	6 months

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Investigators: Principal Investigator: Glen Stevens, DO, PhD, Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2018
• Primary Completion (Actual): April 1, 2022
• Study Completion (Actual): April 1, 2022

Study Registration Dates

• First Submitted: May 14, 2018
• First Submitted That Met QC Criteria: May 14, 2018
• First Posted (Actual): May 24, 2018

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Osimertinib
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Osimertinib
• Other Study ID Numbers: CASE3517

Drug and device information, study documents

• 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