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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03535363
Recruitment Status : Recruiting
First Posted : May 24, 2018
Last Update Posted : January 30, 2019
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE May 14, 2018
First Posted Date  ICMJE May 24, 2018
Last Update Posted Date January 30, 2019
Actual Study Start Date  ICMJE October 26, 2018
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 14, 2018)
Maximum Tolerated Dose (MTD) of Osimertinib with (SRS) [ Time Frame: 4 weeks ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03535363 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2018)
  • Number of patients with progression free survival [ Time Frame: 6 months ]
    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 [ Time Frame: 2 years ]
    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 [ Time Frame: 2 years ]
    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) [ Time Frame: 6 months ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Osimertinib With Stereotactic Radiosurgery (SRS) in Brain Metastases From EGFR Positive NSCLC
Official Title  ICMJE Phase 1 Trial of Osimertinib With Stereotactic Radiosurgery (SRS) in Patients With Brain Metastases From EGFR Positive Non-Small-Cell Lung Cancer (NSCLC)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non-small Cell Lung Cancer
Intervention  ICMJE Drug: Osimertinib
Drug: Osimertinib 80mg or 40mg
Other Name: Tagrisso
Study Arms  ICMJE Experimental: 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
Intervention: Drug: Osimertinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 14, 2018)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Manmeet Ahluwalia, MD 1-866-223-8100
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03535363
Other Study ID Numbers  ICMJE CASE3517
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Case Comprehensive Cancer Center
Study Sponsor  ICMJE Case Comprehensive Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Manmeet Ahluwalia, MD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
PRS Account Case Comprehensive Cancer Center
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP