Clinical Trials /

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

NCT03769103

Description:

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.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: LUOSICNS
  • NCT ID: NCT03769103

Conditions

  • Lung Cancer Non-small Cell Stage IV
  • Brain Metastases

Interventions

DrugSynonymsArms
OsimertinibSRS + Osimertinib

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
SRS + OsimertinibActive ComparatorStereotactic 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.
  • Osimertinib
Osimertinib aloneExperimentalOsimertinib 80mg PO daily
  • Osimertinib

Eligibility 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 ≤ 10 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Intracranial progression free survival
Time Frame:1 year
Safety Issue:
Description:Absence of progressive brain metastases according to the Response Assessment in Neuro-Oncology Brain Metastasis (RANO-BM criteria)

Secondary Outcome Measures

Measure:Intracranial overall response rate
Time Frame:2 years
Safety Issue:
Description:partial or complete response to therapy based on RANO-BM criteria
Measure:Time to whole brain radiotherapy (WBRT)
Time Frame:2 years
Safety Issue:
Description:time from randomization to WBRT
Measure:Time to stereotactic radiosurgery (SRS)
Time Frame:2 years
Safety Issue:
Description:time from randomization to SRS (not including initial SRS in the SRS + osimertinib treatment arm)
Measure:Rate of radionecrosis
Time Frame:2 years
Safety Issue:
Description:according to institutional standards based on radiologic findings with or without pathologic confirmation and multidisciplinary review when required
Measure:Overall survival
Time Frame:2 years
Safety Issue:
Description:defined as time from randomization to death by any cause
Measure:Time to distant progression
Time Frame:2 years
Safety Issue:
Description:time from randomization to progression of extracranial metastases or development of new sites of disease per RECIST 1.1
Measure:Quality of life
Time Frame:2 years
Safety Issue:
Description: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)
Measure:Neurocognitive function
Time Frame:2 years
Safety Issue:
Description:Assessed by Montreal Cognitive Assessment. Total score:30. 1=poor function; 30=good function
Measure:Exposure to osimertinib
Time Frame:2 years
Safety Issue:
Description:Osimertinib dose (40mg or 80mg) for x number of days (max=730 days)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:British Columbia Cancer Agency

Trial Keywords

  • EGFR positive
  • Osimertinib
  • SRS

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