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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 : February 2, 2021
Sponsor:
Collaborators:
AstraZeneca
Princess Margaret Hospital, Canada
Sunnybrook Health Sciences Centre
Information provided by (Responsible Party):
British Columbia Cancer Agency

Tracking Information
First Submitted Date  ICMJE December 3, 2018
First Posted Date  ICMJE December 7, 2018
Last Update Posted Date February 2, 2021
Actual Study Start Date  ICMJE March 19, 2019
Estimated Primary Completion Date April 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 6, 2018)
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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 6, 2018)
  • Intracranial overall response rate [ Time Frame: 2 years ]
    partial or complete response to therapy based on RANO-BM criteria
  • Time to whole brain radiotherapy (WBRT) [ Time Frame: 2 years ]
    time from randomization to WBRT
  • Time to stereotactic radiosurgery (SRS) [ Time Frame: 2 years ]
    time from randomization to SRS (not including initial SRS in the SRS + osimertinib treatment arm)
  • 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
  • Overall survival [ Time Frame: 2 years ]
    defined as time from randomization to death by any cause
  • 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
  • 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)
  • Neurocognitive function [ Time Frame: 2 years ]
    Assessed by Montreal Cognitive Assessment. Total score:30. 1=poor function; 30=good function
  • Exposure to osimertinib [ Time Frame: 2 years ]
    Osimertinib dose (40mg or 80mg) for x number of days (max=730 days)
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 Study of Osimertinib + SRS vs Osimertinib Alone for Brain Metastases in EGFR Positive Patients With NSCLC
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Lung Cancer Non-small Cell Stage IV
  • Brain Metastases
Intervention  ICMJE
  • Drug: Osimertinib
    Daily oral osimertinib
  • Radiation: Stereotactic radiotherapy
    1-5 fractions of stereotactic radiotherapy
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Osimertinib
    • Radiation: Stereotactic radiotherapy
  • Experimental: Osimertinib alone
    Osimertinib 80mg PO daily
    Intervention: Drug: Osimertinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 6, 2018)
76
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2025
Estimated Primary Completion Date April 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
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: 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
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03769103
Other Study ID Numbers  ICMJE LUOSICNS
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party British Columbia Cancer Agency
Study Sponsor  ICMJE British Columbia Cancer Agency
Collaborators  ICMJE
  • AstraZeneca
  • Princess Margaret Hospital, Canada
  • Sunnybrook Health Sciences Centre
Investigators  ICMJE
Principal Investigator: Shilo V Lefresne, MD, FRCPC BC Cancer, Vancouver Centre
Principal Investigator: Cheryl Ho, MD, FRCPC BC Cancer, Vancouver Centre
PRS Account British Columbia Cancer Agency
Verification Date January 2021

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