Non-small Cell Lung Cancer (NSCLC)Phase 2NCT03667820
Study of Osimertinib and Stereotactic Ablative Radiation (SABR) in EGFR Mutant NSCLC
A Phase 2 study testing Osimertinib and SABR in people with Non-small Cell Lung Cancer (NSCLC), run by University of Texas Southwestern Medical Center at 2 sites in United States.
Trial summary
This study evaluates the combination of two well-tolerated therapies, osimertinib and Stereotactic Ablative Radiation (SABR). Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Non-small Cell Lung Cancer (NSCLC)
- What is being tested?
- Osimertinib and SABR
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 2 sitesUnited States
- Study dates
- 26 Sep 2018to 30 Sep 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent
- Age > 18 years
- Advanced EGFR exon 19 or 21 mutant NSCLC, not amenable to curative surgery or radiotherapy. EGFR mutations may be demonstrated by standard, clinically accepted methods, including direct gene sequencing, PCR, and NextGen sequencing.
- World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Patients must have a life expectancy ≥ 12 weeks.
- Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
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- Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
- Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution
- Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
- Male patients should be willing to use barrier contraception.
- Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
- At least one lesion, not previously irradiated, that can be accurately assessed at baseline with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements.
- Adequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
- Absolute neutrophil count >1.5 x 109/L
- Platelet count >100 x 109/L
- Haemoglobin >9.0 g/dL (transfusion is permitted to achieve Hgb ≥9.0 g/dL)
- Alanine aminotransferase <2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or <5 times ULN in the presence of liver metastases
- Aspartate aminotransferase <2.5 times ULN if no demonstrable liver metastases or <5 times ULN in the presence of liver metastases
- Total bilirubin <1.5 times ULN if no liver metastases or <3 times ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases
- Serum Creatinine <1.5 times ULN concurrent with creatinine clearance >50 ml/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN.
Who cannot join
- Involvement in the planning and/or conduct of the study (applies to both sponsor staff and/or staff at the study site).
- Previous treatment with osimertinib or any EGFR TKI.
- Previous treatment with immunotherapy or any check point inhibitors.
- Treatment with an investigational drug within five half-lives of the compound
- 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 CYP3A4 (at least 3 week prior) (Appendix A). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4.
- Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy.
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- Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
- Patients with symptomatic CNS metastases who are neurologically unstable
- Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
- Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTc using Fredericia's formula) > 470 msec
- Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block)
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval
- Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib
- History of hypersensitivity to osimertinib (or drugs with a similar chemical structure or class to osimertinib) or any excipients of these agents
- Males and females of reproductive potential who are not using an effective method of birth control and females who are pregnant or breastfeeding or have a positive (urine or serum) pregnancy test prior to study entry
- 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
- In addition, the following is considered a criterion for exclusion from the exploratory genetic research:
- Previous allogeneic bone marrow transplant.
- Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
City of Hope Medical Center
Duarte, California, 91010
About this study
Official title: Phase II Trial of Osimertinib in Combination With Stereotactic Ablative Radiation (SABR) in EGFR Mutant Advanced Non-Small Cell Lung Cancer (NSCLC)
This study evaluates the combination of two well-tolerated therapies, osimertinib and Stereotactic Ablative Radiation (SABR).
Read the detailed description
Patients with EGFR mutant non-small cell lung cancer will receive the current optimal therapy with osimertinib. After 8 weeks of targeted therapy, there will likely be some persisting lesions that would not have completely regressed. These persisting lesions would likely consist of cells that are less sensitive to targeted therapy. From the data summarized above [14], these persisting lesions are most to subsequently develop resistance and demonstrate progression.
To delay the onset of clinical progression, lesions that persist after 8 weeks of osimertinib therapy and are amenable to stereotactic ablative radiation will be radiated. Osimertinib will be held for 3 days before the first dose of radiation and resumed 3 days after the last dose.
After radiation, all patients will continue osimertinib therapy. If subsequently there is any evidence of progression, there will be an assessment of whether a repeat course of radiation is feasible. If it is feasible to repeat SABR to sites of progression, this will be performed and osimertinib resumed. If SABR is not possible, then a change in systemic therapy will be required.
- Conditions
- Non-small Cell Lung Cancer (NSCLC)
- Being tested
- Osimertinib, SABR
- 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 AZD9291, TAGRISSO
Osimertinib 80mg tablet to be taken once daily.
SABRRadiation
Stereotactic Ablative Radiation (SABR)
| Study group | Role | What they receive |
|---|---|---|
| Osimertinib | Experimental | Osimertinib in combination with Stereotactic Ablative Radiation (SABR) Receives: Drug: Osimertinib; Radiation: SABR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine efficacy of Osimertinib plus SABR in patients with EGFR mutant lung cancer measured by Progression-Free Survival (PFS)
Progression-Free Survival (PFS) as determined by RECIST 1.1 or death (in the absence of progression).
Measured: Every 8 weeks from the time of first dose of study medication until subject death from any cause, assessed up to 300 weeks.
Secondary outcomes (6)
Determine the impact of Osimertinib plus SABR on survival
Overall survival defined as time from the date of initiation of Osimertinib until death of any cause.
Measured: From time of first dose of study medication until subject death from any cause, up to 300 weeks.
Determine the impact of Osimertinib plus SABR on length of response
Duration of response (DoR) defined as the time from documentation of tumor response to disease progression.
Measured: Every 8 weeks from time of first dose of study medication until disease progression or death from any cause, assessed up to 300 weeks.
Determine the impact of Osimertinib plus SABR on the length of time until next therapy needed
Time to subsequent SABR (2nd, 3rd, etc), initiation of new therapy, or death.
Measured: Every 8 Weeks from time of first dose of study medication until subsequent SABR, discontinuation, or disease progression, assessed up to 300 weeks.
Determine the impact of Osimertinib plus SABR on tumor response
Objective response rate (ORR) defined as the proportion of patients with measurable disease who had a response after receiving at least one cycle of therapy.
Measured: Every 8 weeks from time of first study medication dose until discontinuation or subject death from any cause, assessed up to 300 weeks.
Determine the impact of Osimertinib plus SABR on the duration of time while on Osimertinib
Impact defined as time from initiation of Osimertinib to evidence of disease progression by RECIST 1.1, unacceptable toxicity, withdrawal of consent, or discontinuation of the trial for any other reason.
Measured: Every 8 weeks from time of first study medication dose until disease progression, discontinuation or subject death from any cause, up to 300 weeks.
Number and type of adverse events related to Osimertinib plus SABR as assessed by CTCAE v4.0
Defined as the risk to patients by using Osimertinib plus SABR and the degree to which overt adverse events of the Osimertinib plus SABR can be tolerated.
Measured: From time of first study medication dose through treatment period and including the follow-up period every 4 months following last dose of study medication, until subject death from any cause, up to 48 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2018
- Study start26 Sep 2018
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-small Cell Lung Cancer (NSCLC)Studies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Principal investigator, Sawsan Rashdan, University of Texas Southwestern Medical Center
- Investigators
- Sawsan Rashdan, MD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03667820
- Sponsor's protocol ID
- STU 122017-017
- Status last verified
- Oct 2025
- First submitted
- 29 Jun 2018
- Last updated
- 4 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Sampath S, Rashdan S, Iyengar P, Mickel TA, Zhang S, Ahn C, Gao A, Dowell JE, Zhang Y, Westover KD, Cole SM, Amini A, Rock A, Massarelli E, Koczywas M, Gerber DE. Osimertinib plus consolidative radiotherapy for advanced EGFR mutant non-small cell lung cancer: a multicentre, single-arm, phase 2 trial. EClinicalMedicine. 2025 Aug 26;87:103435. doi: 10.1016/j.eclinm.2025.103435. eCollection 2025 Sep.
PubMed 41054436
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Osimertinib in Combination With Stereotactic Ablative Radiation (SABR) in EGFR Mutant Advanced Non-Small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT03667820
- Acronym / sponsor ID
- STU 122017-017
- Conditions
- Non-small Cell Lung Cancer (NSCLC)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 41 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 26 Sep 2018 (actual)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 12 Sep 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.
This study evaluates the combination of two well-tolerated therapies, osimertinib and Stereotactic Ablative Radiation (SABR).
Detailed description
Patients with EGFR mutant non-small cell lung cancer will receive the current optimal therapy with osimertinib. After 8 weeks of targeted therapy, there will likely be some persisting lesions that would not have completely regressed. These persisting lesions would likely consist of cells that are less sensitive to targeted therapy. From the data summarized above [14], these persisting lesions are most to subsequently develop resistance and demonstrate progression.
To delay the onset of clinical progression, lesions that persist after 8 weeks of osimertinib therapy and are amenable to stereotactic ablative radiation will be radiated. Osimertinib will be held for 3 days before the first dose of radiation and resumed 3 days after the last dose.
After radiation, all patients will continue osimertinib therapy. If subsequently there is any evidence of progression, there will be an assessment of whether a repeat course of radiation is feasible. If it is feasible to repeat SABR to sites of progression, this will be performed and osimertinib resumed. If SABR is not possible, then a change in systemic therapy will be required.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Osimertinib | Experimental | Drug: Osimertinib, Radiation: SABROsimertinib in combination with Stereotactic Ablative Radiation (SABR) |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Written informed consent
- Age > 18 years
- Advanced EGFR exon 19 or 21 mutant NSCLC, not amenable to curative surgery or radiotherapy. EGFR mutations may be demonstrated by standard, clinically accepted methods, including direct gene sequencing, PCR, and NextGen sequencing.
- World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Patients must have a life expectancy ≥ 12 weeks.
Key exclusion criteria (20 listed)
- Involvement in the planning and/or conduct of the study (applies to both sponsor staff and/or staff at the study site).
- Previous treatment with osimertinib or any EGFR TKI.
- Previous treatment with immunotherapy or any check point inhibitors.
- Treatment with an investigational drug within five half-lives of the compound
- 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 CYP3A4 (at least 3 week prior) (Appendix A). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4.
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: AZD9291, TAGRISSOOsimertinib 80mg tablet to be taken once daily. | Drug | Osimertinib |
| SABRStereotactic Ablative Radiation (SABR) | Radiation | Osimertinib |
Primary outcome
Determine efficacy of Osimertinib plus SABR in patients with EGFR mutant lung cancer measured by Progression-Free Survival (PFS)
Time frame: Every 8 weeks from the time of first dose of study medication until subject death from any cause, assessed up to 300 weeks.
Progression-Free Survival (PFS) as determined by RECIST 1.1 or death (in the absence of progression).
6 secondary outcomes
Determine the impact of Osimertinib plus SABR on survival
Time frame: From time of first dose of study medication until subject death from any cause, up to 300 weeks.
Determine the impact of Osimertinib plus SABR on length of response
Time frame: Every 8 weeks from time of first dose of study medication until disease progression or death from any cause, assessed up to 300 weeks.
Determine the impact of Osimertinib plus SABR on the length of time until next therapy needed
Time frame: Every 8 Weeks from time of first dose of study medication until subsequent SABR, discontinuation, or disease progression, assessed up to 300 weeks.
Determine the impact of Osimertinib plus SABR on tumor response
Time frame: Every 8 weeks from time of first study medication dose until discontinuation or subject death from any cause, assessed up to 300 weeks.
Determine the impact of Osimertinib plus SABR on the duration of time while on Osimertinib
Time frame: Every 8 weeks from time of first study medication dose until disease progression, discontinuation or subject death from any cause, up to 300 weeks.
Number and type of adverse events related to Osimertinib plus SABR as assessed by CTCAE v4.0
Time frame: From time of first study medication dose through treatment period and including the follow-up period every 4 months following last dose of study medication, until subject death from any cause, up to 48 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2025.
- Derived from this study: PubMed 41054436Sampath S, Rashdan S, Iyengar P, Mickel TA, Zhang S, Ahn C, Gao A, Dowell JE, Zhang Y, Westover KD, Cole SM, Amini A, Rock A, Massarelli E, Koczywas M, Gerber DE. Osimertinib plus consolidative radiotherapy for advanced EGFR mutant non-small cell lung cancer: a multicentre, single-arm, phase 2 trial. EClinicalMedicine. 2025 Aug 26;87:103435. doi: 10.1016/j.eclinm.2025.103435. eCollection 2025 Sep.
- Individual participant dataSharing planned: Undecided
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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.
Sawsan Rashdan, MD principal investigator
University of Texas Southwestern Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Osimertinib and SABR in people with Non-small Cell Lung Cancer (NSCLC), run by University of Texas Southwestern Medical 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 20 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: under way, not looking for participants, as of the sponsor's last update on 4 Nov 2025. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Determine efficacy of Osimertinib plus SABR in patients with EGFR mutant lung cancer measured by Progression-Free Survival (PFS) (time frame: Every 8 weeks from the time of first dose of study medication until subject death from any cause, assessed up to 300 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03667820, which also lists 1 linked publication.
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 4 Nov 2025.