Clinical trial NCT03769103: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Lung Cancer Non-small Cell Stage IV
Brain Metastases
Keywords: EGFR positive
Osimertinib
SRS
Lead sponsor: British Columbia Cancer Agency
Sponsor class: OTHER
Collaborators: name: AstraZeneca
name: Princess Margaret Hospital, Canada
name: Sunnybrook Health Sciences Centre
First posted: 2018-12-07
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 ≤ 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

Primary outcomes:
measure: Intracranial progression free survival
timeFrame: 1 year
Secondary outcomes:
measure: Intracranial overall response rate
timeFrame: 2 years
measure: Time to whole brain radiotherapy (WBRT)
timeFrame: 2 years
measure: Time to stereotactic radiosurgery (SRS)
timeFrame: 2 years
measure: Rate of radionecrosis
timeFrame: 2 years
measure: Overall survival
timeFrame: 2 years
measure: Time to distant progression
timeFrame: 2 years
measure: Quality of life
timeFrame: 2 years
measure: Neurocognitive function
timeFrame: 2 years
measure: Exposure to osimertinib
timeFrame: 2 years
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: BC Cancer, Vancouver Centre
state: British Columbia
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: BC Cancer, Vancouver Centre
name: Shilo V Lefresne, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: BC Cancer, Vancouver Centre
name: Cheryl Ho, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: