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

NCT03769103 | Active Not Recruiting Phase 2

• 1 other identifier: LUOSICNS
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

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.

Conditions

Lung Cancer Non-small Cell Stage IV; Brain Metastases

Keywords

EGFR positive; Osimertinib; SRS

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Intracranial overall response rate

  2 years

• Time to whole brain radiotherapy (WBRT)

  2 years

• Time to stereotactic radiosurgery (SRS)

  2 years

• Rate of radionecrosis

  2 years

• Overall survival

  2 years

Study Arms (2)

SRS + Osimertinib

ACTIVE COMPARATOR

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; Radiation: Stereotactic radiotherapy

Osimertinib alone

EXPERIMENTAL

Osimertinib 80mg PO daily

Drug: Osimertinib

Interventions

Osimertinib DRUG

Daily oral osimertinib

Osimertinib alone; SRS + Osimertinib

Stereotactic radiotherapy RADIATION

1-5 fractions of stereotactic radiotherapy

SRS + Osimertinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• British Columbia Cancer Agency: lead
• AstraZeneca: collaborator
• Princess Margaret Hospital, Canada: collaborator
• Sunnybrook Health Sciences Centre: collaborator

Study Sites (3)

BC Cancer, Vancouver Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Interventions

osimertinib; Radiosurgery

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Shilo V Lefresne, MD, FRCPC

  BC Cancer, Vancouver Centre

  PRINCIPAL INVESTIGATOR

• Cheryl Ho, MD, FRCPC

  BC Cancer, Vancouver Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2018
• First Posted: December 7, 2018
• Study Start: March 19, 2019
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2025
• Last Updated: October 31, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3)