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

Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03535363
• Other study ID #: CASE3517
• Status: Completed
• Phase: Phase 1
• Start date: October 26, 2018
• Est. completion date: April 1, 2022

Study information

• Verified date: March 2024
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: April 1, 2022
• Est. primary completion date: April 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Neoplasms
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer
• NSCLC

Intervention

Drug:
• Osimertinib
Drug: Osimertinib 80mg or 40mg

Locations

Country	Name	City	State
United States	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Maimi Cancer Institute - Baptist Health South Florida	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Case Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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