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

NCT ID: NCT03535363

Last Updated: 2024-03-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-26
• Study Completion Date: 2022-04-01

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.

Conditions

NSCLC; Non-small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Osimertinib

Intervention Type: DRUG

Drug: Osimertinib 80mg or 40mg

Interventions

Osimertinib

Drug: Osimertinib 80mg or 40mg

Intervention Type: DRUG

Other Intervention Names

Tagrisso

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Case Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Glen Stevens, DO, PhD

Role: PRINCIPAL_INVESTIGATOR

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Locations

Maimi Cancer Institute - Baptist Health South Florida

Miami, Florida, United States

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

CASE3517

Identifier Type: -

Identifier Source: org_study_id