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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 3, 2020
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

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

Condition or disease Intervention/treatment Phase
NSCLC Non-small Cell Lung Cancer Drug: Osimertinib Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : October 26, 2018
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Osimertinib

Arm Intervention/treatment
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
Drug: Osimertinib
Drug: Osimertinib 80mg or 40mg
Other Name: Tagrisso

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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)

  2. 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

  3. 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)

  4. 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03535363

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Contact: Manmeet Ahluwalia, MD 1-866-223-8100

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United States, Ohio
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44195
Contact: Manmeet Ahluwalia, MD    866-223-8100   
Principal Investigator: Manmeet Ahluwalia, MD         
Sponsors and Collaborators
Case Comprehensive Cancer Center
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Principal Investigator: Manmeet Ahluwalia, MD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

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Responsible Party: Case Comprehensive Cancer Center Identifier: NCT03535363    
Other Study ID Numbers: CASE3517
First Posted: May 24, 2018    Key Record Dates
Last Update Posted: January 3, 2020
Last Verified: January 2020

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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
Keywords provided by Case Comprehensive Cancer Center:
Additional relevant MeSH terms:
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Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Bronchial Neoplasms
Carcinoma, Non-Small-Cell Lung
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action