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

Brain Metastases Clinical Trial

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT03769103
• Other study ID #: LUOSICNS
• Status: Recruiting
• Phase: Phase 2
• Start date: March 19, 2019
• Est. completion date: April 2025

Study information

• Verified date: January 2021
• Source: British Columbia Cancer Agency
• Contact: Shilo V Lefresne, MD, FRCPC
• Phone: 604 877 6000
• Email: SLefresne[@]bccancer.bc.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 76
• Est. completion date: April 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Metastases
• Brain Neoplasms
• Carcinoma, Non-Small-Cell Lung
• Lung Cancer Non-small Cell Stage IV
• Lung Neoplasms
• Neoplasm Metastasis

Intervention

Drug:
• Osimertinib
Daily oral osimertinib

Radiation:
• Stereotactic radiotherapy
1-5 fractions of stereotactic radiotherapy

Locations

Country	Name	City	State
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	BC Cancer, Vancouver Centre	Vancouver	British Columbia

Sponsors (4)

Lead Sponsor	Collaborator
British Columbia Cancer Agency	AstraZeneca, Princess Margaret Hospital, Canada, Sunnybrook Health Sciences Centre

Country where clinical trial is conducted

Canada, 

Outcome

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