NSCLCPhase 1NCT03535363
Osimertinib With Stereotactic Radiosurgery (SRS) in Brain Metastases From EGFR Positive NSCLC
A Phase 1 study testing Osimertinib in people with NSCLC and Non-small Cell Lung Cancer, run by Case Comprehensive Cancer Center at 2 sites in United States.
Trial summary
Investigating potential of controlling brain metastases in patients with EGFR positive NSCLC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC, Non-small Cell Lung Cancer
- What is being tested?
- Osimertinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 2 sitesUnited States
- Study dates
- 26 Oct 2018to 1 Apr 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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)
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- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
Maimi Cancer Institute - Baptist Health South Florida
Miami, Florida, 33176
About this study
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)
Investigating potential of controlling brain metastases in patients with EGFR positive NSCLC.
Read the 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.
- Conditions
- NSCLC, Non-small Cell Lung Cancer
- Being tested
- Osimertinib
- Keywords
- Osimertinib
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OsimertinibDrug
Also called Tagrisso
Drug: Osimertinib 80mg or 40mg
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Osimertinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Osimertinib with (SRS)
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.
Measured: 4 weeks
Secondary outcomes (4)
Number of patients with progression free survival
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)
Measured: 6 months
Length of overall survival
To assess the overall survival (OS) in patients with EGFR positive NSCLC Brain Metastases treated with Osimertinib and SRS
Measured: 2 years
Difference in outcome vs. standard of care
To compare results of our clinical trial to patients with EGFR positive NSCLC with brain metastases treated with SRS alone (1-10 brain Metastases)
Measured: 2 years
Intra-cranial and Extra-cranial Overall Response Rate (ORR)
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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2018
- Study start26 Oct 2018
- Primary completion1 Apr 2022
- Study completion1 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLCStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Glen Stevens, DO, PhD, Principal investigator, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03535363
- Sponsor's protocol ID
- CASE3517
- Status last verified
- Mar 2024
- First submitted
- 14 May 2018
- Last updated
- 13 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03535363
- Acronym / sponsor ID
- CASE3517
- Conditions
- NSCLC, Non-small Cell Lung Cancer
- Keywords
- Osimertinib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 26 Oct 2018 (actual)
- Primary completion
- 1 Apr 2022 (actual)
- Study completion
- 1 Apr 2022 (actual)
- First posted
- 24 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Maximum Tolerated Dose of Osimertinib with standard of care | Experimental | Drug: OsimertinibFor 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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)
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OsimertinibAlso: TagrissoDrug: Osimertinib 80mg or 40mg | Drug | Maximum Tolerated Dose of Osimertinib with standard of care |
Primary outcome
Maximum Tolerated Dose (MTD) of Osimertinib with (SRS)
Time frame: 4 weeks
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.
4 secondary outcomes
Number of patients with progression free survival
Time frame: 6 months
Length of overall survival
Time frame: 2 years
Difference in outcome vs. standard of care
Time frame: 2 years
Intra-cranial and Extra-cranial Overall Response Rate (ORR)
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Glen Stevens, DO, PhD principal investigator
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Osimertinib in people with NSCLC and Non-small Cell Lung Cancer, run by Case Comprehensive Cancer Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) of Osimertinib with (SRS) (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2024.