Clinical Trials /

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

NCT03535363

Description:

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

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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)

Clinical Trial IDs

  • ORG STUDY ID: CASE3517
  • NCT ID: NCT03535363

Conditions

  • NSCLC
  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
OsimertinibTagrissoMaximum Tolerated Dose of Osimertinib with standard of care

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Maximum Tolerated Dose of Osimertinib with standard of careExperimentalFor 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
  • Osimertinib

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD) of Osimertinib with (SRS)
Time Frame:4 weeks
Safety Issue:
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.

Secondary Outcome Measures

Measure:Number of patients with progression free survival
Time Frame:6 months
Safety Issue:
Description: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)
Measure:Length of overall survival
Time Frame:2 years
Safety Issue:
Description:To assess the overall survival (OS) in patients with EGFR positive NSCLC Brain Metastases treated with Osimertinib and SRS
Measure:Difference in outcome vs. standard of care
Time Frame:2 years
Safety Issue:
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)
Measure:Intra-cranial and Extra-cranial Overall Response Rate (ORR)
Time Frame:6 months
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Case Comprehensive Cancer Center

Trial Keywords

  • Osimertinib

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