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

See Contacts and Locations

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

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

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

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

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

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

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