Study of Osimertinib + SRS vs Osimertinib Alone for Brain Metastases in EGFR Positive Patients With 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. |
ClinicalTrials.gov Identifier: NCT03769103 |
Recruitment Status :
Recruiting
First Posted : December 7, 2018
Last Update Posted : February 2, 2021
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Lung Cancer Non-small Cell Stage IV Brain Metastases | Drug: Osimertinib Radiation: Stereotactic radiotherapy | Phase 2 |
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 |

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 |
- 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)
- 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)

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

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
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 |
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 |
Principal Investigator: | Shilo V Lefresne, MD, FRCPC | BC Cancer, Vancouver Centre | |
Principal Investigator: | Cheryl Ho, MD, FRCPC | BC Cancer, Vancouver Centre |
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: | February 2, 2021 |
Last Verified: | January 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
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 |
EGFR positive Osimertinib SRS |
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 |