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

Study 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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT03769103
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	British Columbia Cancer Agency
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Shilo V Lefresne, MD, FRCPCCheryl Ho, MD, FRCPC
Principal Investigator Affiliation	BC Cancer, Vancouver CentreBC Cancer, Vancouver Centre
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other, Industry
Overall Status	Recruiting
Countries	Canada
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Lung Cancer Non-small Cell Stage IV, Brain Metastases

Arms & Interventions

Arms

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.

Experimental: Osimertinib alone

Osimertinib 80mg PO daily

Interventions

Drug: - Osimertinib

Daily oral osimertinib

Radiation: - Stereotactic radiotherapy

1-5 fractions of stereotactic radiotherapy

Contact a Trial Team

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