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Study of Osimertinib + SRS vs Osimertinib Alone for Brain Metastases in EGFR Positive Patients With NSCLC

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ClinicalTrials.gov Identifier: NCT03769103
Recruitment Status : Recruiting
First Posted : December 7, 2018
Last Update Posted : November 5, 2019
Sponsor:
Collaborators:
AstraZeneca
Princess Margaret Hospital, Canada
Sunnybrook Health Sciences Centre
Information provided by (Responsible Party):
British Columbia Cancer Agency

Study Description
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Brief Summary:
This open-label, multicenter, randomized phase II study will evaluate the usage of osimertinib alone for brain metastases compared to SRS and osimertinib in patients with newly diagnosed, treatment naiive EGFR positive lung cancer.

Condition or disease Intervention/treatment Phase
Lung Cancer Non-small Cell Stage IV Brain Metastases Drug: Osimertinib Radiation: Stereotactic radiotherapy Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 76 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open Label, Multicenter, Phase II Study of Patients With Treatment Naïve Metastatic Epidermal Growth Factor Receptor (EGFR) Mutation-Positive Non-Small Cell Lung Cancer (NSCLC) With Brain Metastases Randomized to Stereotactic Radiosurgery (SRS) and Osimertinib or Osimertinib Alone
Actual Study Start Date : March 19, 2019
Estimated Primary Completion Date : April 2025
Estimated Study Completion Date : April 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Osimertinib

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: SRS + Osimertinib
Stereotactic radiotherapy will be delivered in 1-5 fractions to each brain metastases according to the volume and location of the metastases and clinician discretion. Osimertinib will start 1-7 days post radiotherapy.
 Drug: Osimertinib
Daily oral osimertinib

Radiation: Stereotactic radiotherapy
1-5 fractions of stereotactic radiotherapy
Experimental: Osimertinib alone
Osimertinib 80mg PO daily
 Drug: Osimertinib
Daily oral osimertinib


Outcome Measures
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Primary Outcome Measures :
  1. Intracranial progression free survival [ Time Frame: 1 year ]
    Absence of progressive brain metastases according to the Response Assessment in Neuro-Oncology Brain Metastasis (RANO-BM criteria)


Secondary Outcome Measures :
  1. Intracranial overall response rate [ Time Frame: 2 years ]
    partial or complete response to therapy based on RANO-BM criteria

  2. Time to whole brain radiotherapy (WBRT) [ Time Frame: 2 years ]
    time from randomization to WBRT

  3. Time to stereotactic radiosurgery (SRS) [ Time Frame: 2 years ]
    time from randomization to SRS (not including initial SRS in the SRS + osimertinib treatment arm)

  4. Rate of radionecrosis [ Time Frame: 2 years ]
    according to institutional standards based on radiologic findings with or without pathologic confirmation and multidisciplinary review when required

  5. Overall survival [ Time Frame: 2 years ]
    defined as time from randomization to death by any cause

  6. Time to distant progression [ Time Frame: 2 years ]
    time from randomization to progression of extracranial metastases or development of new sites of disease per RECIST 1.1

  7. Quality of life [ Time Frame: 2 years ]
    Assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30. Subscales for: general presence of symptoms in patients with cancer question 1-28 (1=Not at all; 4=very much); overall health/quality of life question 29-30 (1=very poor; 7=excellent) & EORTC-QLQ Brain Neoplasm (BN)20: Subscales for presence of symptoms in patients with brain tumours question 31-50 (1=Not at all; 4=very much)

  8. Neurocognitive function [ Time Frame: 2 years ]
    Assessed by Montreal Cognitive Assessment. Total score:30. 1=poor function; 30=good function

  9. Exposure to osimertinib [ Time Frame: 2 years ]
    Osimertinib dose (40mg or 80mg) for x number of days (max=730 days)


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

Inclusion Criteria:

  • Able to provide written informed consent by patient or legally acceptable representative
  • Meets the criteria in the approved regulatory indication for first line treatment with osimertinib and agree to the restrictions, monitoring, and dose-adjustment criteria stipulated in the associated product label
  • Epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations (either alone or in combination with other EGFR mutations)
  • No prior systemic therapy except neoadjuvant, adjuvant or concurrent chemotherapy given greater than 3 months prior to enrollment on study
  • Asymptomatic or minimally symptomatic brain metastases (ie. Headache, nausea, or seizure responsive to dexamethasone/analgesic/antiepileptic on stable doses of medications for a minimum of 3 days)
  • Brain metastases must meet the following criteria on a diagnostic MRI: at least one lesion can be classified as measurable disease per RANO-BM, ≤ 10 brain or brainstem metastases, ≤ 30 mm and brainstem metastases must be ≤ 5 mm, metastases > 5 mm from the optic nerve or chiasm
  • ECOG performance status 0-2
  • Life expectancy > 6 months
  • Willing to abstain from sexual activity or willing to use double-barrier method during sexual intercourse

Exclusion Criteria:

  • Previous treatment with osimertinib, or any other EGFR TKI
  • Patient with symptomatic brain metastases causing any neurologic deficit (not including headache, nausea, or medically controlled seizure)
  • Multiple sclerosis
  • Pacemaker or MRI-incompatible metal in the body
  • Allergy to gadolinium MRI contrast
  • Brain metastasis requiring surgery for decompression
  • Leptomeningeal disease
  • Previous cranial RT, or surgery for brain metastases
  • Uncontrolled systemic lupus erythematosis, scleroderma or other connective tissue disorders considered a contraindication for radiotherapy
  • Active cancer from another anatomical site within 5 years (non-melanomatous skin and cervical cancers permitted)
  • Any medical or non-medical issue that would render patient unable to reliably complete regular QOL and neurocognitive assessments
  • Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
  • Treatment with an investigational drug within five half-lives of the compound or 3 months, whichever is greater
  • Patients with symptomatic CNS metastases who are neurologically unstable
  • Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of cytochrome P450 (CYP) 3A4
  • Patients taking any drugs that are known to prolong QT interval that can't be withdrawn prior to Osimertinib
  • Pregnant or breastfeeding
Contacts and Locations
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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 ClinicalTrials.gov identifier (NCT number): NCT03769103


Contacts
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Contact: Shilo V Lefresne, MD, FRCPC 604 877 6000 ext 2673 SLefresne@bccancer.bc.ca
Contact: Cheryl Ho, MD, FRCPC 604 877 6000 cho@bccancer.bc.ca

Locations
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Canada, British Columbia
BC Cancer, Vancouver Centre Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Contact: Shilo Lefresne, MD    604 877 6000 ext 2673    slefresne@bccancer.bc.ca   
Contact: Cheryl Ho, MD    604 877 6000 ext 2445    cho@bccancer.bc.ca   
Canada, Ontario
Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada
Contact: Adrian Sacher         
Contact: David Shultz         
Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada
Contact: Mark Doherty         
Contact: Arjun Sahgal         
Sponsors and Collaborators
British Columbia Cancer Agency
AstraZeneca
Princess Margaret Hospital, Canada
Sunnybrook Health Sciences Centre
Investigators
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Principal Investigator: Shilo V Lefresne, MD, FRCPC BC Cancer, Vancouver Centre
Principal Investigator: Cheryl Ho, MD, FRCPC BC Cancer, Vancouver Centre
More Information
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Responsible Party: British Columbia Cancer Agency
ClinicalTrials.gov Identifier: NCT03769103    
Other Study ID Numbers: LUOSICNS
First Posted: December 7, 2018    Key Record Dates
Last Update Posted: November 5, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by British Columbia Cancer Agency:
EGFR positive
Osimertinib
SRS
Additional relevant MeSH terms:
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Lung Neoplasms
Neoplasm Metastasis
Brain Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Neoplastic Processes
Pathologic Processes
 Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Osimertinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action