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

Primary Purpose

NSCLC, Non-small Cell Lung Cancer

Status

Active

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Osimertinib

About this trial

This is an interventional treatment trial for NSCLC focused on measuring Osimertinib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Maimi Cancer Institute - Baptist Health South Florida
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Maximum Tolerated Dose of Osimertinib with standard of care

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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)

Length of overall survival

To assess the overall survival (OS) in patients with EGFR positive NSCLC Brain Metastases treated with Osimertinib and SRS

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)

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.

Full Information

NCT ID

NCT03535363

First Posted

May 14, 2018

Last Updated

October 19, 2023

Sponsor

Case Comprehensive Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT03535363

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

October 26, 2018 (Actual)

Primary Completion Date

April 1, 2022 (Actual)

Study Completion Date

February 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Case Comprehensive Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

NSCLC, Non-small Cell Lung Cancer

Keywords

Osimertinib

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Maximum Tolerated Dose of Osimertinib with standard of care

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Osimertinib

Other Intervention Name(s)

Tagrisso

Intervention Description

Drug: Osimertinib 80mg or 40mg

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose (MTD) of Osimertinib with (SRS)

Description

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.

Time Frame

4 weeks

Secondary Outcome Measure Information:

Title

Number of patients with progression free survival

Description

Time Frame

6 months

Title

Length of overall survival

Description

To assess the overall survival (OS) in patients with EGFR positive NSCLC Brain Metastases treated with Osimertinib and SRS

Time Frame

2 years

Title

Difference in outcome vs. standard of care

Description

To compare results of our clinical trial to patients with EGFR positive NSCLC with brain metastases treated with SRS alone (1-10 brain Metastases)

Time Frame

2 years

Title

Intra-cranial and Extra-cranial Overall Response Rate (ORR)

Description

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Glen Stevens, DO, PhD

Organizational Affiliation

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Maimi Cancer Institute - Baptist Health South Florida

City

Miami

State/Province

Florida

ZIP/Postal Code

33176

Country

United States

Facility Name

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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