Clinical trial NCT03535363: Osimertinib With Stereotactic Radiosurgery (SRS) in Brain Metastases From EGFR Positive NSCLC
Official title: Phase 1 Trial of Osimertinib With Stereotactic Radiosurgery (SRS) in Patients With Brain Metastases From EGFR Positive Non-Small-Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: NSCLC
Non-small Cell Lung Cancer
Keywords: Osimertinib
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2018-05-24
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Investigating potential of controlling brain metastases in patients with EGFR positive NSCLC.

Detailed description: In patients with EGFR positive NSCLC with 1-10 brain metastases, we are investigating whether we can control the macro brain metastases with Stereotactic Radiosurgery (SRS) and control the micro metastases with targeted agent Osimertinib and avoid whole brain radiation that could potentially lead to significant cognitive decline.

Eligibility criteria: Inclusion Criteria:

* Confirmed pathology of EGFR mutation positive NSCLC with new brain metastases.
* Ability to care for self and ability to walk 50% of waking hours (ECOG Performance Status of 0-2)
* 1-10 brain metastases with intra-cranial brain metastasis must measure 3cm or less in the greatest dimension.
* Hemoglobin ≥9 g/dL, White Blood Count Absolute ≥3.0 x 10\^9/L, Granulocyte count ≥1.5 x 10\^9/L, and platelet count ≥100 x 10\^9/L
* Serum Bilirubin ≤ 1.5 x upper limit of normal (ULN)
* AST and/or ALT ≤ 2 ULN (≤ 5 x ULN when clearly attributable to liver metastases)
* Serum creatinine ≤ 1.5 ULN or calculated creatinine clearance \> 60ml/min
* For women of childbearing potential-Negative pregnancy test within one week prior to start of therapy.
* For all sexually active male and female patients of reproductive potential, employ two methods of highly effective and acceptable forms of contraception throughout the study and for 120 days following the final dose of osimertinib.

Exclusion Criteria:

* Patients with leptomeningeal metastases documented by MRI or cerebrospinal fluid (CSF).
* Significant intratumoral or peritumoral hemorrhage
* Brain metastases within 5 mm of the optic chiasm or optic nerve
* Brainstem metastases
* Gastrointestinal disorders with diarrhea as a major symptom
* Clinically significant or uncontrolled cardiac disease (NYHA functional classification of 3 or 4)
* Pre-existing interstitial lung disease or pneumonitis
* Unable to undergo brain MRI
* HIV or Hepatitis B or C
* Prior treatments must be resolved to an asymptomatic state at time of enrollment
* Medical conditions that could cause safety risks
* Currently receiving investigational cancer therapy.
* Mean QT interval corrected heart rate (QTc)≥470ms calculated from 3 EKGs
* Left Ventricular Ejection Fraction (LVEF) ≤ 50%
* Use of strong CYP3A inhibitors
* Use of strong CYP3A4 inducers
* Use of potent CYP2C8 inhibitors
* Hypersensitivity to osimertinib or any of its ingredients
* corneal ulceration
* pregnant or breast-feeding

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Osimertinib with (SRS)
timeFrame: 4 weeks
Secondary outcomes:
measure: Number of patients with progression free survival
timeFrame: 6 months
measure: Length of overall survival
timeFrame: 2 years
measure: Difference in outcome vs. standard of care
timeFrame: 2 years
measure: Intra-cranial and Extra-cranial Overall Response Rate (ORR)
timeFrame: 6 months
Other outcomes:
Locations:
city: Miami
country: United States
facility: Maimi Cancer Institute - Baptist Health South Florida
state: Florida
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
name: Glen Stevens, DO, PhD
role: PRINCIPAL_INVESTIGATOR
References: