Description:
Investigating potential of controlling brain metastases in patients with EGFR positive NSCLC.
Title
- Brief Title: 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)
Clinical Trial IDs
- ORG STUDY ID:
CASE3517
- NCT ID:
NCT03535363
Conditions
- NSCLC
- Non-small Cell Lung Cancer
Interventions
Drug | Synonyms | Arms |
---|
Osimertinib | Tagrisso | Maximum Tolerated Dose of Osimertinib with standard of care |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Maximum Tolerated Dose of Osimertinib with standard of care | Experimental | For patients with 1-10 brain metastases, begin daily Osimeritinib 0-7 days prior to stereotactic radiosurgery (SRS), provide daily Osimeritinib concurrently with radiotherapy, followed by maintenance Osimeritinib until disease progression, withdrawal, or unacceptable toxicity. Dose Level 1: 80mg daily. Dose Level -1: 40mg daily | |
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Maximum Tolerated Dose (MTD) of Osimertinib with (SRS) |
Time Frame: | 4 weeks |
Safety Issue: | |
Description: | To determine the safety, tolerability and maximum tolerated dose of Osimertinib, when administered in combination with SRS in patients with EGFR positive NSCLC with brain metastases. |
Secondary Outcome Measures
Measure: | Number of patients with progression free survival |
Time Frame: | 6 months |
Safety Issue: | |
Description: | To assess the six-month intra-cranial and extra-cranial progression-free survival (PFS-6) in patients with EGFR positive NSCLC brain metastases treated with Osimertinib and SRS (PFS is defined as the time from clinical registration to intra-or extra-cranial tumor progression or death) |
Measure: | Length of overall survival |
Time Frame: | 2 years |
Safety Issue: | |
Description: | To assess the overall survival (OS) in patients with EGFR positive NSCLC Brain Metastases treated with Osimertinib and SRS |
Measure: | Difference in outcome vs. standard of care |
Time Frame: | 2 years |
Safety Issue: | |
Description: | To compare results of our clinical trial to patients with EGFR positive NSCLC with brain metastases treated with SRS alone (1-10 brain Metastases) |
Measure: | Intra-cranial and Extra-cranial Overall Response Rate (ORR) |
Time Frame: | 6 months |
Safety Issue: | |
Description: | To assess Overall response rate (ORR) both intracranial and extracranial, defined as the proportion of patients with a best overall confirmed response of complete response (CR) or partial response (PR) in the whole body as assessed per RECIST 1.1 by the investigator. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Case Comprehensive Cancer Center |
Trial Keywords
Last Updated
March 19, 2021