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Metastatic Non Small Cell Lung CancerPhase 2OUTRUNNCT03497767

A Randomised Phase II Trial of Osimertinib With or Without SRS for EGFR Mutated NSCLC With Brain Metastases

A Phase 2 study testing Osimertinib and Stereotactic Radiosurgery (SRS) in people with Metastatic Non Small Cell Lung Cancer, run by Trans Tasman Radiation Oncology Group at 13 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

20-40% of patients with NSCLC will develop brain metastases at some point during their course of disease. Osimertinib has demonstrated intracranial activity in EFGR mutated NSCLC with leptomeningeal disease in the phase 1 BLOOM study. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Non Small Cell Lung Cancer
What is being tested?
Osimertinib and Stereotactic Radiosurgery (SRS)
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
13 sitesin 2 countries
Study dates
15 Aug 2019to 30 Apr 2024
Phase
Phase 2
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

  • Provided written informed consent
  • Has reached the age of majority in the country of treatment (i.e. ≥ 18 years in Australia; ≥ 21 years in Singapore)
  • Histological or cytological documented NSCLC
  • Metastatic NSCLC, not amenable to curative surgery or curative radiotherapy
  • Brain metastases that meet the following criteria;
  • ≤ 10 lesion/s visible and measurable on protocol screening MRI;
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  • At least one brain metastases able to be treated with SRS
  • Definite but small brain metastases not for SRS treatment due to size, as per physician discretion, are included in the total
  • Equivocal small lesions are not included in the total
  • No single brain metastasis exceeding 30mm longest diameter
  • Total brain metastasis volume ≤ 15cc;
  • Total brain metastases volume on protocol screening MRI should be using the formula (4/3) x (3.14159265359) x (1/2 x size lesion in centimetre)3. Table 1: Brain metastases volume estimates provides an estimate of the volume of brain metastases based on the size of the lesion
  • Diagnosed de novo (i.e. at the same time with a new diagnosis of NSCLC) or developed as a new site of progression while on first line EGFR TKI
  • NOTE: Surgery as part of local practice for the management of brain metastasis is allowed but must be completed between 2 to 4 weeks prior to randomisation. Patients must still fulfil criteria 5a, 5b and 5d pre-surgery, and have at least one target lesion post-surgery to be eligible for the study. Lesions that are partially or completely resected should not be used as a target lesion for MRI assessment.
  • Documented EGFR mutation;
  • Patients who developed brain metastases as a site of disease progression while on first line EGFR TKIs must have T790M mutation.
  • Documented EGFR mutation (at any time since the initial diagnosis of NSCLC) known to be sensitive to Osimertinib - These include exon 19 del; L858R (exon 21); G719X (exon 18); L861G (exon 21); S768I (exon 20) and T790M (exon 20) NOTE: Mutation analysis is to be done as per local practice. Please see section 7.1.1 for the recommended clinical practice for analysis.
  • Are one of the following cohorts:
  • First-line metastatic cancer: All newly diagnosed participants with documented sensitising EGFR mutation (criterion 6) and intracranial metastasis (criterion 5), with/without extracranial disease
  • Second-line metastatic cancer (T790M+): Participants who progressed after first-line 1st or 2nd generation EGFR TKI therapy with intracranial progression (criterion 5), with/without extracranial disease and have documented T790M mutation
  • Second-line metastatic cancer (T790M-): Participants with no T790M mutation who progressed after first-line 1st or 2nd generation EGFR TKI therapy with intracranial progression (criterion 5) but has no extracranial disease
  • Second-line metastatic cancer (T790M-): Participants with no T790M mutation who progressed after first-line 1st or 2nd generation EGFR TKI therapy with intracranial progression (criterion 5) but has stable extracranial disease
  • Karnofsky performance status 60-100 (ECOG performance status ≤2) with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks
  • Female patients who;
  • are willing to use adequate contraceptive measures until 6 weeks after the final dose of study treatment
  • are not breast feeding
  • have a negative pregnancy test prior to the start of dosing if of child bearing potential or have evidence of non-child bearing potential by fulfilling one of the following criteria at screening:
  • Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments ii. Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) levels in the post-menopausal range for the institution iii. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
  • Male patients who are willing to use barrier contraception (i.e. condoms) until 4 months after the final dose of study treatment

Who cannot join

  • Treatment with any of the following:
  • Prior systemic therapy for patients with newly diagnosed metastatic NSCLC and brain metastases de novo.
  • NOTE: Prior adjuvant chemotherapy or chemotherapy used as radio sensitisation followed by maintenance immunotherapy for non-resectable early stage NSCLC are allowed if such treatments were more than 6 months ago.
  • Prior whole brain radiotherapy (WBRT)
  • Radiologically progressive brain metastasis that underwent prior SRS (second line patients)
  • Previous treatment with Osimertinib or a 3rd generation EGFR TKI.
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  • Previous treatment with checkpoint inhibitors immunotherapy for metastatic NSCLC.
  • Major surgery within 4 weeks of randomisation (excluding placement of vascular access and surgery as part of local practice for the management of brain metastases, as outlined in inclusion criterion 5).
  • Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of randomisation.
  • Medications or herbal supplements known to be potent inducers of CYP3A4 and are unable to stop use within the recommended wash out period prior to receiving the first dose of Osimertinib, see Table 7: Medications to avoid and withdrawal periods and Table 8 NOTE: All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4
  • An investigational drug within five half-lives of the compound or 3 months, whichever is greater.
  • Any other cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days of randomisation.
  • Any unresolved toxicities from prior therapy greater than CTCAE grade 1 (with the exception of alopecia grade 2) at the time of starting study treatment.
  • Spinal cord compression unless asymptomatic and stable.
  • Leptomeningeal disease.
  • Moderate or severe symptomatic brain metastases defined as per Radiation Therapy Oncology Group acute morbidity grade 3 to 4.
  • NOTE:
  • Grade 3 refers to neurological findings requiring hospitalisation for initial management.
  • Grade 4 refers to serious neurological impairment including paralysis, coma or seizures more than three times per week despite medication and requires hospitalization.
  • Brain metastases in the brainstem.
  • 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 jeopardize compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
  • 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.
  • Any of the following cardiac criteria:
  • Resting corrected QT interval (QTc) > 470 msec, obtained from an electrocardiogram (ECG).
  • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block or second degree heart block.
  • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities (including: Serum/plasma potassium < LLN; Serum/plasma magnesium < LLN; Serum/plasma calcium < LLN), 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.
  • Patients with congenital long QT syndrome (CLQTS)
  • Past medical history of Interstitial Lung Disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
  • Inadequate 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 < 90 g/L
  • Alanine aminotransferase (ALT) > 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 (AST) > 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.
  • Creatinine > 1.5 times ULN concurrent with creatinine clearance < 50ml/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is > 1.5 times ULN.
  • History of hypersensitivity of drugs with a similar chemical structure or class to Osimertinib or any excipients of these agents.
  • Involvement in the planning and conduct of the study
  • Judgement 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.

Trial locations and contacts

13 sites in 2 countries.

13 sites in 2 countries

Australia12 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia

  • Princess Alexandra Hospital

    Brisbane, Queensland, 4102

  • ICON Cancer Centre Greenslopes

    Brisbane, Queensland, 4120

  • Peter MacCallum Cancer Center

    Melbourne, Victoria, 3002

  • Monash Health

    Melbourne, Victoria, 3175

  • Calvary Mater

    Newcastle, New South Wales, 2298

  • Sir Charles Gairdner

    Perth, Western Australia

  • Liverpool Hospital

    Sydney, New South Wales, 2002

  • St. Vincents Hospital

    Sydney, New South Wales, 2010

  • Westmead Hospital

    Sydney, New South Wales, 2145

  • Blacktown Hospital

    Sydney, New South Wales, 2148

  • St George Hospital

    Sydney, New South Wales, 2217

Other trials in Australia

Singapore1 site

  • National University Hospital

    Singapore, 119074

Other trials in Singapore

About this study

Official title: A Randomised Phase II Trial of Osimertinib With or Without Stereotactic Radiosurgery for EGFR Mutated Non-Small Cell Lung Cancer (NSCLC) With Brain Metastases

20-40% of patients with NSCLC will develop brain metastases at some point during their course of disease. Osimertinib has demonstrated intracranial activity in EFGR mutated NSCLC with leptomeningeal disease in the phase 1 BLOOM study. Stereotactic radiosurgery (SRS) is one of the standard local treatment for patients with limited number of brain metastases. Currently, it is unclear whether adding SRS to Osimertinib will result in superior intracranial disease control in patients with EGFR mutated NSCLC with brain metastases diagnosed de novo or developed while on first line EGFR tyrosine kinase inhibitors (TKIs) such as Erlotinib and Gefinitib.

The aim of this study is to compare the effects of Osimertinib alone versus SRS plus Osimertinib on intra-cranial disease control in EGFR mutated NSCLC with brain metastases diagnosed or developed while on first line EGFR tyrosine kinase inhibitors.

Being tested
Osimertinib, Stereotactic Radiosurgery (SRS)
Keywords
Non Small Cell Lung Cancer (NSCLC), EGFR mutation, Osimertinib, Stereotactic Radiosurgery
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

    All participants will receive a dose of Osimertinib 80mg once daily

  • Stereotactic Radiosurgery (SRS)Radiation

    Dose and fractionation depend on lesion size. All SRS must be completed within 21 days of randomisation and all lesions are to be treated within 7 days.

Study groups in NCT03497767
Study groupRoleWhat they receive
OsimertinibExperimental80mg Osimerinib taken once daily
Receives: Drug: Osimertinib
Stereotactic Radiosurgery + OsimertinibExperimentalUpfront Stereotactic Radiosurgery (SRS) followed by 80mg Osimerinib taken once daily
Receives: Drug: Osimertinib; Radiation: Stereotactic Radiosurgery (SRS)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Intracranial progression free survival at 12 months

    To assess the efficacy of Osimertinib with deferred local brain metastases directed therapies compared with upfront SRS followed by Osimertinib by assessment of intracranial progression free survival at 12 months.

    Measured: 12 months post randomisation

Secondary outcomes (5)

  1. Use of salvage whole-brain radiotherapy (WBRT)

    To assess the effect of Osimertinib with deferred local brain metastases directed therapies compared with upfront SRS followed by Osimertinib on use of salvage whole-brain radiotherapy (WBRT) +/- neurosurgery.

    Measured: 18 months post randomisation

  2. Local brain failure

    To assess the effect of Osimertinib with deferred local brain metastases directed therapies compared with upfront SRS followed by Osimertinib on local brain failure.

    Measured: 18 months post randomisation

  3. Distant brain failure

    To assess the effect of Osimertinib with deferred local brain metastases directed therapies compared with upfront SRS followed by Osimertinib on distant brain failure.

    Measured: 18 months post randomisation

  4. Extra-cranial progression

    To assess the effect of Osimertinib with deferred local brain metastases directed therapies compared with upfront SRS followed by Osimertinib on extra-cranial progression.

    Measured: 18 months post randomisation

  5. Overall Survival

    To further assess the efficacy of Osimertinib with deferred local brain metastases directed therapies compared with upfront SRS followed by Osimertinib in terms of overall survival.

    Measured: 18 months post randomisation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Apr 2018
  2. Study start15 Aug 2019
  3. Primary completion30 Apr 2024
  4. Study completion30 Apr 2024

Resources

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03497767
Sponsor's protocol ID
TROG 17.02
Acronym
OUTRUN
Status last verified
May 2024
First submitted
26 Feb 2018
Last updated
31 May 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Lee CK, Lefresne S, Soon YY, Robledo K, Nichol A, Sahgal A, Pinkham MB, Melosky B, Huang Y, McDermott R, Tham IWK, Parmar A, Tey JCS, Liu M, Solomon BJ, Sacher A, Leong CN, Laskin J, Koh WY, Menjak IB, Ang Y, Shultz DB, Low JL, Doherty M, Yong C, Lim MC, Tan AP, Soo RA, Hegi-Johnson F, Ho C. Osimertinib and Stereotactic Radiosurgery for Brain Metastases in EGFR-Mutated Lung Cancer: The STARLET Joint Analysis of OUTRUN and LUOSICNS Randomized Trials. J Thorac Oncol. 2026 May;21(5):103549. doi: 10.1016/j.jtho.2026.01.001. Epub 2026 Jan 12.

    PubMed 41534788

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Osimertinib and Stereotactic Radiosurgery (SRS) in people with Metastatic Non Small Cell Lung Cancer, run by Trans Tasman Radiation Oncology Group at 13 sites in 2 countries.

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 29 inclusion and 39 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 31 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Australia, Singapore. 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?

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?

Intracranial progression free survival at 12 months (time frame: 12 months post randomisation). 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 NCT03497767, 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 31 May 2024.

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