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

NCT03535363 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CASE3517
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

NSCLC; Non-small Cell Lung Cancer

Keywords

Osimertinib

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Number of patients with progression free survival

  6 months

• Length of overall survival

  2 years

• Difference in outcome vs. standard of care

  2 years

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

  6 months

Study Arms (1)

Maximum Tolerated Dose of Osimertinib with standard of care

EXPERIMENTAL

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

Interventions

Osimertinib DRUG

Drug: Osimertinib 80mg or 40mg

Also known as: Tagrisso

Maximum Tolerated Dose of Osimertinib with standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (2)

Maimi Cancer Institute - Baptist Health South Florida

Miami, Florida, 33176, United States

Location

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib

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

• Glen Stevens, DO, PhD

  Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2018
• First Posted: May 24, 2018
• Study Start: October 26, 2018
• Primary Completion: April 1, 2022
• Study Completion: April 1, 2022
• Last Updated: March 13, 2024

Record last verified: 2024-03

Locations

US (2)