Non-small Cell Lung Cancer Stage IIPhase 1/2STILENCT03383302
SBRT With Immunotherapy in Early Stage Non-small Cell Lung Cancer: Tolerability and Lung Effects
A Phase 1/2 study testing Stereotactic body radiotherapy and Nivolumab in people with Non-small Cell Lung Cancer Stage II and Non-small Cell Lung Cancer Stage I, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
This is a single arm, multi-centre, phase II open label study of nivolumab with stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer. SBRT will be delivered in either 3 or 5 fractions for peripheral disease or 8 fractions in central disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer Stage II, Non-small Cell Lung Cancer Stage I
- What is being tested?
- Stereotactic body radiotherapy and Nivolumab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 8 Feb 2018to 26 Jun 2025
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Subjects must have signed and dated a Research Ethics Committee (REC) approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care
- Subjects must be willing and able to comply with scheduled visits, treatment schedule, and laboratory tests
- ECOG Performance status (PS) 0-2
- Minimum of first 5 patients to be PS 0-1
- PS 2 patients to be enrolled only following recommendation by the Independent Data Monitoring Committee (IDMC)
- Patients with histological diagnosis of NSCLC, all histological sub-types are eligible
Show all 21Show fewer
- Not suitable for surgery because of medical co-morbidity, lesion is technically inoperable or patient declines surgery after surgical assessment (or option of assessment)
- Single or synchronous/metachronous primary NSCLC lesions, tumour stage T1-3 (≤6cm), N0 M0 (UICC v.8) as determined by the local MDT based on minimum investigations of CT chest/abdomen within 8 weeks and FDG-PET within 6 weeks of 1st fraction of SBRT. Where the radiological nodal status is equivocal then only eligible if possible nodal disease is subsequently confirmed as pathologically negative with mediastinoscopy or endoscopic bronchial or oesophageal ultra-sound biopsy as necessary
- For synchronous tumours one lesion must have a histological diagnosis of NSCLC. For the other lesion a radiological diagnosis of NSCLC as determined by lung MDT is sufficient. (Upon diagnosis of metachronous primary NSCLC these lesions require biopsy for trial entry)
- Metachronous (single) primary NSCLC lesions, tumour stage T1-3 (≤6cm) N0 M0 (UICC v.8) presenting after previous treatment of T1-3(≤6cm) N0 M0 (UICC v.8) with surgery or SBRT are eligible for inclusion. Lung constraints must be able to feasibly achieved (according to dose constraints in 7.1.2
- Tumour stage T1-3 termed as 'central' disease within 2cm of main airways and proximal bronchial tree, but not abutting these structures (ultra-central), are suitable for entry. Up to 5 patients with 'central' primary NSCLC (up to 2 lesions) can be enrolled and followed up for 3 months following their final fraction of radiotherapy at which stage an IDMC meeting is required to assess further 'central' primary NSCLC recruitment
- Screening laboratory values must meet the following criteria prior to commencement of treatment:
- WBCs ≥ 2000/μL ii) Neutrophils ≥1500/μL iii) Platelets ≥ 100 X10³/μL iv) Haemoglobin ≥ 9.0 g/dL v) Serum creatinine of ≤ 1.5 X ULN or creatinine clearance (CrCl)/glomerular filtration rate (GFR) > 40 mL/minute (using Cockcroft/Gault formula or as assessed by local practice)
- . Female CrCl= [(140- age in years) X weight in kg X 0.85) ÷ (72 X serum creatinine in mg/ dL)]
- . Male CrCl= [(140- age in years) X weight in kg X 1.00) ÷ (72 X serum creatinine in mg/ dL)] vi) AST ≤ 3 X ULN vii) ALT ≤ 3 X ULN viii) Total bilirubin ≤ 1.5 X ULN (except subjects with Gilbert Syndrome, who must have total bilirubin < 50 μmol/L)
- No prior adjuvant or foreseen neo-adjuvant or adjuvant chemotherapy is allowed
- Males and Females ≥ 18 years of age
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) in the screening period and within 24 hours prior to the start of study drug.
- Women must not be breastfeeding during the study treatment and for a period up to 23 weeks post treatment completion
- WOCBP must agree to follow instructions for method(s) of contraception during the study treatment and for a total of 23 weeks post treatment completion
- Males who are sexually active with WOCBP must agree to follow instructions for method(s) for contraception for a total of 31 weeks post treatment completion.
Who cannot join
- Any tumour that is not clinically definable on the treatment planning CT scan e.g. surrounded by consolidation or atelectasis
- 'Ultra-central' tumours, i.e. those adjacent to the hilar structures, with the gross tumour volume directly abutting a main bronchus
- Subjects with active, known autoimmune disease. Subjects with Type I diabetes mellitus, residual hypothyroidism due to an autoimmune condition requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol.
- Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of the first dose of study drug administration. Inhaled or topical steroids and adrenal replacement steroid doses > 10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease
- Subjects with previous malignancies (except non-melanoma skin cancers, early stage NSCLC treated with SBRT or surgery and current lesion not considered to be relapsed NSCLC, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period
- Patient with known interstitial lung disease or active, non-infectious pneumonitis
Show all 16Show fewer
- Previous conventional radiotherapy to the chest or mediastinum. Patients who have had previous breast radiotherapy may be eligible at the discretion of the Chief Investigator
- Any serious or uncontrolled medical disorder or active infection that, in the opinion of the Investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the subject to receive protocol therapy
- All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to Grade 1 (NCI CTCAE v.4.0) or baseline before administration of study drug
- Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study treatment
- Subjects who received prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) or who have previously taken part in a randomized BMS clinical trial for nivolumab or ipilimumab
- Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
- Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBVsAg) test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection
- o Patients with a positive HCV antibody but no detection of HCV RNA indicating no current infection are eligible
- Patients who have received a live vaccine within 30 days prior to the first dose of trial treatment
- History of allergy to study drug components
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Stereotactic Body Radiotherapy Radiotherapy With Immunotherapy in Early Stage Non-small Cell Lung Cancer: Tolerability and Lung Effects
This is a single arm, multi-centre, phase II open label study of nivolumab with stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer.
SBRT will be delivered in either 3 or 5 fractions for peripheral disease or 8 fractions in central disease. A flat dose of 240 mg nivolumab infusion will begin after the final fraction of SBRT, within 24 hours and typically on the same day. Nivolumab will subsequently be given every 2 weeks at a flat dose of 240 mg for a further 13 cycles followed by Nivolumab 480mg Q4W for 7 cycles until 20 cycles in total are complete, unless any study drug discontinuation criteria are met. Treatment (20 cycles) will take a minimum of 1 year to complete but may exceed this timeframe if treatment delays are encountered.
Read more
(Patients who have enrolled on Nivolumab Q2W 240mg regimen for 26 cycles and are beyond cycle 14 will receive 26 cycles Q2W in total to complete treatment).
Assessment of toxicities will be performed at each clinic visit during treatment, at 30 days after the final nivolumab infusion and until 100 days after the final nivolumab infusion. Changes in spirometry values and PFTs will be assessed throughout the trial.
Relapse rates will be assessed with staging CT scans at 3, 6, 12, 18 and 24 months post SBRT.
An exploratory assessment will be made of the effect pre-treatment pulmonary function tests (PFTs) have on outcome measures.
Read the detailed description
This is a single arm, multi-centre, phase II open label study of nivolumab with stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer.
Current United Kingdom (UK) guidelines for SBRT do not specify exclusion pulmonary function criteria. Severely reduced Forced Expiratory Volume in 1 second (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) (<40% predicted) are common reasons for medical inoperability leading to the choice of SBRT. In a large prospective study of patients undergoing SBRT, poor baseline PFT was not predictive of toxicity including pneumonitis. At the 2 year follow up, the mean decline in percentage of predicted forced expiratory volume in one second (FEV1) and diffusion capacity of carbon monoxide (DLCO) were only 5.8% and 6.3% respectively. Focal SBRT is a well-tolerated procedure and acute complications are generally transient. Symptomatic radiation pneumonitis has been reported at rates of 4-25% of patients.
Drug induced pneumonitis is reported at 6% in lung cancer patients receiving nivolumab and at 2% with grade 3-4 toxicity. Of note, such rates are similar or lower to other drugs used in NSCLC including docetaxel for which no PFT restrictions occur. In this study, frequent assessment of spirometry values may help to predict patients that are developing subclinical pneumonitis and prompt for early intervention.
SBRT will be delivered in either 3 or 5 fractions for peripheral disease or 8 fractions in central disease. A flat dose of 240 mg nivolumab infusion will begin after the final fraction of SBRT, within 24 hours and typically on the same day. Nivolumab will subsequently be given every 2 weeks at a flat dose of 240 mg for a further 13 cycles followed by Nivolumab 480mg Q4W for 7 cycles until 20 cycles in total are complete, unless any study drug discontinuation criteria are met. The study will recruit 31 patients. We anticipate it will take approximately 18 months to recruit 31 patients.
The study will include subjects with histologically verified NSCLC deemed by a local multidisciplinary team (MDT) to have anatomical stage T1-3 [≤6cm] N0 M0 by means of computed tomography (CT) and fludeoxyglucose-positron emission tomography (FDG-PET) , amenable to radical treatment with SBRT and inoperable due to medical co-morbidity, being technically unresectable or patient declining surgery after offer of surgical assessment.
Subjects will receive nivolumab as per the treatment schedule unless any withdrawal criteria are met. The first nivolumab infusion will be given after the final fraction of SBRT, within 24 hours and generally on the same day. Clinical follow up and investigations are as detailed in the schedule of assessment.
The first 5 patients to enroll must have Eastern Co-operative Oncology Group (ECOG) performance status (PS) < 2 at the time of first dose of investigational medical product (IMP). An Independent Data Monitoring Committee (IDMC) will meet when the first 5 patients have reached 3 months follow up from their 1st dose of nivolumab or have withdrawn consent to follow-up. Patients that have enrolled but did not receive IMP will be replaced. The IDMC, if satisfied with the safety data from the initial 5 patients, may recommend escalation to include recruitment of patients with ECOG performance status of 2. Further patients of PS <2 may enroll while awaiting the outcome of the IDMC meeting.
The IDMC will perform a further safety review when the first 5 patients enrolled with ECOG performance status 2 have reached 3 months follow up from their final fraction of radiotherapy or have withdrawn consent to follow-up. Patients that have enrolled but did not receive IMP will be replaced. Further patients with ECOG performance status 2 will not be able to enroll unless recommendation is given by the IDMC. In the event that 5 PS 2 patients have not enrolled by the point that the 15th recruited patient has reached 3 months follow up, then there will be a further mandated IDMC meeting to assess safety data from the study. Patients may continue to enroll while awaiting the outcome of this IDMC meeting.
Assessment of toxicities will be performed at each clinic visit during treatment, at 30 days after the final nivolumab infusion and until 100 days after the final nivolumab infusion. Changes in spirometry values and PFTs will be assessed throughout the trial.
Relapse rates will be assessed with staging CT scans at 3, 6, 12, 18 and 24 months post SBRT.
An exploratory assessment will be made of the effect pre-treatment pulmonary function tests (PFTs) have on outcome measures.
- Being tested
- Stereotactic body radiotherapy, Nivolumab
- Keywords
- Non-small cell lung cancer, NSCLC
- 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.
Stereotactic body radiotherapyRadiation
Also called SBRT
Patients will receive a total of 54 Gy if delivered in 3 fractions, 55 Gy if delivered in 5 fractions or 60 Gy if delivered in 8 fractions.
NivolumabDrug
Also called L01XC17, Opdivo
Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody, that binds to the PD-1 receptor and blocks interaction with its ligands PD-L1 and PD-L2. Nivolumab will be administered intravenously at a flat dose of 240 mg q2w over 30 minutes for 13 cycles followed by 480mg q4w over 60 minutes for 7 cycles, until 20 cycles in total to complete (a minimum of 1 year of treatment if no delays are encountered).
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 Tolerabilty | Experimental | This is a single arm study of nivolumab administered on completion of stereotactic body radiotherapy (SBRT) to patients with early stage NSCLC. The first 5 patients to enroll must have Eastern Co-operative Oncology Group (ECOG) performance status < 2 at the time of first dose of investigational medical product (IMP). An Independent Data Monitoring Committee (IDMC) will meet when the first 5 patients have reached 3 months follow up from their 1st dose of nivolumab or have withdrawn consent to follow-up. The IDMC, if satisfied with the safety data from the initial 5 patients, may recommend escalation to include recruitment of patients with ECOG performance status of 2. Receives: Radiation: Stereotactic body radiotherapy; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of Lung Toxicity (Pneumonitis) From Treatment With Nivolumab After SBRT for Early Stage NSCLC
Number of participants with grade ≥ 3 pneumonitis from treatment with nivolumab after stereotactic body radiotherapy (SBRT) within 6 months of the final fraction of SBRT (2-3 weeks treatment duration depending on dosing). A rate that exceeds 20% will be deemed unacceptable and will lead to a rejection of the null hypothesis.
Measured: Six months from final dose of SBRT (2-3 weeks) administered for each patient
Secondary outcomes (7)
Adverse Events (Toxicity) by Worst Grade
Rates of toxicity will be summarised as worst toxicity grade during treatment as per CTCAE v. 4 after treatment with Nivolumab following SBRT.
Measured: 24 months from last dose of SBRT (2-3 weeks treatment duration)
Proportion of Patient Receiving 1,2,3,4,5 and 6 Doses of Nivolumab Within 16 Weeks of Commencing Adjuvant Nivolumab After SBRT for Early Stage NSCLC
The proportion of patients receiving 1,2,3,4,5 and 6 doses within 16 weeks of commencing treatment are reported with a 95% exact confidence interval.
Measured: Within 16 weeks of each patient commencing treatment with Nivolumab after SBRT (2-3 weeks duration)
Disease Relapse - To Assess Local, Local-regional and Distant Disease Relapse Rates
All rates of relapse (local, loco-regional and distant rates) were evaluated using the 30 patients in the efficacy population and presented as a proportion with a 95% exact binomial confidence interval. Time to event analysis was not performed within these endpoints as the number of events were too low.
Measured: 24 months from last dose of SBRT (2-3 weeks duration)
Overall Survival
Overall survival (OS) was evaluated for 29 out of the 31 patients in the efficacy population (1 patient withdrew during SBRT and no SBRT start date was recorded) OS rates at 12 and 24 months are reported.
Measured: Overall survival rate (OS) at 12 and 24 months
Disease Free Survival
Disease-free survival (DFS) was evaluated for 29 out of the 31 patients in the efficacy population (1 patient withdrew during SBRT and no SBRT start date was recorded) DFS rates at 6, 12 and 24 months are reported.
Measured: Disease Free Survival (DFS) at 6, 12 and 24 months
Health-related Quality of Life (HRQoL) Using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) in Patients Treated With Nivolumab After SBRT for Early Stage NSCLC
Estimation of the health-related quality of life (HRQoL) score at each time point of analysis (screening, then at 3, 6, 9, 12, 18, 24 months post-SBRT). QOL questionnaires will be scored according to the EORTC Quality of Life Questionnaire (QLQ-C30) version 3 scoring manual. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level, in cases of a functioning scale a better outcome, but for symptom scales a higher score represents a worse outcome.
Measured: 24 months from last dose of SBRT (2-3 weeks duration)
HRQoL Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) in Patients Treated With Nivolumab After SBRT for Early Stage NSCLC.
Estimation of HRQoL in patients treated with Nivolumab after SBRT for early stage NSCLC using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at each time point of analysis (screening, then at 3, 6, 9, 12, 18, 24 months post-SBRT). QOL data will be scored according to the QLQ-LC13 scoring manual, which includes one multi-item scale to assess dyspnea, and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and haemoptysis, all had a score ranging from 0 to 100, where a higher score represents a high level of symptomatology/problems.
Measured: 24 months from last dose of SBRT (2-3 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2017
- Study start8 Feb 2018
- Primary completion12 Aug 2024
- Study completion26 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-small Cell Lung Cancer Stage IIStudies of the same condition, open and under way.
- More trials run by Royal Marsden NHS Foundation TrustThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a single arm, phase Ib/II open label study of nivolumab administered on completion of SBRT to patients with early stage NSCLC.
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal Marsden NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Merina Ahmed, Principal investigator, Royal Marsden NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03383302
- Sponsor's protocol ID
- CCR4644
- Acronym
- STILE
- Status last verified
- Jul 2026
- First submitted
- 23 Nov 2017
- Last updated
- 17 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mirsadraee S, Oswal D, Alizadeh Y, Caulo A, van Beek E Jr. The 7th lung cancer TNM classification and staging system: Review of the changes and implications. World J Radiol. 2012 Apr 28;4(4):128-34. doi: 10.4329/wjr.v4.i4.128.
PubMed 22590666
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stereotactic Body Radiotherapy Radiotherapy With Immunotherapy in Early Stage Non-small Cell Lung Cancer: Tolerability and Lung Effects
- ClinicalTrials.gov ID
- NCT03383302
- Acronym / sponsor ID
- STILE / CCR4644
- Keywords
- Non-small cell lung cancer, NSCLC
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Royal Marsden NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 8 Feb 2018 (actual)
- Primary completion
- 12 Aug 2024 (actual)
- Study completion
- 26 Jun 2025 (actual)
- First posted
- 26 Dec 2017 (actual)
- Results
- Posted 17 Jul 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single arm, multi-centre, phase II open label study of nivolumab with stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer.
SBRT will be delivered in either 3 or 5 fractions for peripheral disease or 8 fractions in central disease. A flat dose of 240 mg nivolumab infusion will begin after the final fraction of SBRT, within 24 hours and typically on the same day. Nivolumab will subsequently be given every 2 weeks at a flat dose of 240 mg for a further 13 cycles followed by Nivolumab 480mg Q4W for 7 cycles until 20 cycles in total are complete, unless any study drug discontinuation criteria are met. Treatment (20 cycles) will take a minimum of 1 year to complete but may exceed this timeframe if treatment delays are encountered.
(Patients who have enrolled on Nivolumab Q2W 240mg regimen for 26 cycles and are beyond cycle 14 will receive 26 cycles Q2W in total to complete treatment).
Assessment of toxicities will be performed at each clinic visit during treatment, at 30 days after the final nivolumab infusion and until 100 days after the final nivolumab infusion. Changes in spirometry values and PFTs will be assessed throughout the trial.
Relapse rates will be assessed with staging CT scans at 3, 6, 12, 18 and 24 months post SBRT.
An exploratory assessment will be made of the effect pre-treatment pulmonary function tests (PFTs) have on outcome measures.
Detailed description
This is a single arm, multi-centre, phase II open label study of nivolumab with stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer.
Current United Kingdom (UK) guidelines for SBRT do not specify exclusion pulmonary function criteria. Severely reduced Forced Expiratory Volume in 1 second (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) (<40% predicted) are common reasons for medical inoperability leading to the choice of SBRT. In a large prospective study of patients undergoing SBRT, poor baseline PFT was not predictive of toxicity including pneumonitis. At the 2 year follow up, the mean decline in percentage of predicted forced expiratory volume in one second (FEV1) and diffusion capacity of carbon monoxide (DLCO) were only 5.8% and 6.3% respectively. Focal SBRT is a well-tolerated procedure and acute complications are generally transient. Symptomatic radiation pneumonitis has been reported at rates of 4-25% of patients.
Drug induced pneumonitis is reported at 6% in lung cancer patients receiving nivolumab and at 2% with grade 3-4 toxicity. Of note, such rates are similar or lower to other drugs used in NSCLC including docetaxel for which no PFT restrictions occur. In this study, frequent assessment of spirometry values may help to predict patients that are developing subclinical pneumonitis and prompt for early intervention.
SBRT will be delivered in either 3 or 5 fractions for peripheral disease or 8 fractions in central disease. A flat dose of 240 mg nivolumab infusion will begin after the final fraction of SBRT, within 24 hours and typically on the same day. Nivolumab will subsequently be given every 2 weeks at a flat dose of 240 mg for a further 13 cycles followed by Nivolumab 480mg Q4W for 7 cycles until 20 cycles in total are complete, unless any study drug discontinuation criteria are met. The study will recruit 31 patients. We anticipate it will take approximately 18 months to recruit 31 patients.
The study will include subjects with histologically verified NSCLC deemed by a local multidisciplinary team (MDT) to have anatomical stage T1-3 [≤6cm] N0 M0 by means of computed tomography (CT) and fludeoxyglucose-positron emission tomography (FDG-PET) , amenable to radical treatment with SBRT and inoperable due to medical co-morbidity, being technically unresectable or patient declining surgery after offer of surgical assessment.
Subjects will receive nivolumab as per the treatment schedule unless any withdrawal criteria are met. The first nivolumab infusion will be given after the final fraction of SBRT, within 24 hours and generally on the same day. Clinical follow up and investigations are as detailed in the schedule of assessment.
The first 5 patients to enroll must have Eastern Co-operative Oncology Group (ECOG) performance status (PS) < 2 at the time of first dose of investigational medical product (IMP). An Independent Data Monitoring Committee (IDMC) will meet when the first 5 patients have reached 3 months follow up from their 1st dose of nivolumab or have withdrawn consent to follow-up. Patients that have enrolled but did not receive IMP will be replaced. The IDMC, if satisfied with the safety data from the initial 5 patients, may recommend escalation to include recruitment of patients with ECOG performance status of 2. Further patients of PS <2 may enroll while awaiting the outcome of the IDMC meeting.
The IDMC will perform a further safety review when the first 5 patients enrolled with ECOG performance status 2 have reached 3 months follow up from their final fraction of radiotherapy or have withdrawn consent to follow-up. Patients that have enrolled but did not receive IMP will be replaced. Further patients with ECOG performance status 2 will not be able to enroll unless recommendation is given by the IDMC. In the event that 5 PS 2 patients have not enrolled by the point that the 15th recruited patient has reached 3 months follow up, then there will be a further mandated IDMC meeting to assess safety data from the study. Patients may continue to enroll while awaiting the outcome of this IDMC meeting.
Assessment of toxicities will be performed at each clinic visit during treatment, at 30 days after the final nivolumab infusion and until 100 days after the final nivolumab infusion. Changes in spirometry values and PFTs will be assessed throughout the trial.
Relapse rates will be assessed with staging CT scans at 3, 6, 12, 18 and 24 months post SBRT.
An exploratory assessment will be made of the effect pre-treatment pulmonary function tests (PFTs) have on outcome measures.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a single arm, phase Ib/II open label study of nivolumab administered on completion of SBRT to patients with early stage NSCLC.
| Arm | Type | Receives |
|---|---|---|
| Arm 1 Tolerabilty | Experimental | Radiation: Stereotactic body radiotherapy, Drug: NivolumabThis is a single arm study of nivolumab administered on completion of stereotactic body radiotherapy (SBRT) to patients with early stage NSCLC. The first 5 patients to enroll must have Eastern Co-operative Oncology Group (ECOG) performance status < 2 at the time of first dose of investigational medical product (IMP). An Independent Data Monitoring Committee (IDMC) will meet when the first 5 patients have reached 3 months follow up from their 1st dose of nivolumab or have withdrawn consent to follow-up. The IDMC, if satisfied with the safety data from the initial 5 patients, may recommend escalation to include recruitment of patients with ECOG performance status of 2. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Subjects must have signed and dated a Research Ethics Committee (REC) approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care
- Subjects must be willing and able to comply with scheduled visits, treatment schedule, and laboratory tests
- ECOG Performance status (PS) 0-2
- Minimum of first 5 patients to be PS 0-1
- PS 2 patients to be enrolled only following recommendation by the Independent Data Monitoring Committee (IDMC)
Key exclusion criteria (16 listed)
- Any tumour that is not clinically definable on the treatment planning CT scan e.g. surrounded by consolidation or atelectasis
- 'Ultra-central' tumours, i.e. those adjacent to the hilar structures, with the gross tumour volume directly abutting a main bronchus
- Subjects with active, known autoimmune disease. Subjects with Type I diabetes mellitus, residual hypothyroidism due to an autoimmune condition requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol.
- Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of the first dose of study drug administration. Inhaled or topical steroids and adrenal replacement steroid doses > 10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease
- Subjects with previous malignancies (except non-melanoma skin cancers, early stage NSCLC treated with SBRT or surgery and current lesion not considered to be relapsed NSCLC, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period
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 |
|---|---|---|
| Stereotactic body radiotherapyAlso: SBRTPatients will receive a total of 54 Gy if delivered in 3 fractions, 55 Gy if delivered in 5 fractions or 60 Gy if delivered in 8 fractions. | Radiation | Arm 1 Tolerabilty |
| NivolumabAlso: L01XC17, OpdivoNivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody, that binds to the PD-1 receptor and blocks interaction with its ligands PD-L1 and PD-L2. Nivolumab will be administered intravenously at a flat dose of 240 mg q2w over 30 minutes for 13 cycles followed by 480mg q4w over 60 minutes for 7 cycles, until 20 cycles in total to complete (a minimum of 1 year of treatment if no delays are encountered). | Drug | Arm 1 Tolerabilty |
Primary outcome
Assessment of Lung Toxicity (Pneumonitis) From Treatment With Nivolumab After SBRT for Early Stage NSCLC
Time frame: Six months from final dose of SBRT (2-3 weeks) administered for each patient
Number of participants with grade ≥ 3 pneumonitis from treatment with nivolumab after stereotactic body radiotherapy (SBRT) within 6 months of the final fraction of SBRT (2-3 weeks treatment duration depending on dosing). A rate that exceeds 20% will be deemed unacceptable and will lead to a rejection of the null hypothesis.
7 secondary outcomes
Adverse Events (Toxicity) by Worst Grade
Time frame: 24 months from last dose of SBRT (2-3 weeks treatment duration)
Proportion of Patient Receiving 1,2,3,4,5 and 6 Doses of Nivolumab Within 16 Weeks of Commencing Adjuvant Nivolumab After SBRT for Early Stage NSCLC
Time frame: Within 16 weeks of each patient commencing treatment with Nivolumab after SBRT (2-3 weeks duration)
Disease Relapse - To Assess Local, Local-regional and Distant Disease Relapse Rates
Time frame: 24 months from last dose of SBRT (2-3 weeks duration)
Overall Survival
Time frame: Overall survival rate (OS) at 12 and 24 months
Disease Free Survival
Time frame: Disease Free Survival (DFS) at 6, 12 and 24 months
Health-related Quality of Life (HRQoL) Using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) in Patients Treated With Nivolumab After SBRT for Early Stage NSCLC
Time frame: 24 months from last dose of SBRT (2-3 weeks duration)
HRQoL Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) in Patients Treated With Nivolumab After SBRT for Early Stage NSCLC.
Time frame: 24 months from last dose of SBRT (2-3 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22590666Mirsadraee S, Oswal D, Alizadeh Y, Caulo A, van Beek E Jr. The 7th lung cancer TNM classification and staging system: Review of the changes and implications. World J Radiol. 2012 Apr 28;4(4):128-34. doi: 10.4329/wjr.v4.i4.128.
- Individual participant dataSharing planned: No
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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.
Merina Ahmed principal investigator
Royal Marsden NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Stereotactic body radiotherapy and Nivolumab in people with Non-small Cell Lung Cancer Stage II and Non-small Cell Lung Cancer Stage I, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.
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 21 inclusion and 16 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 17 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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 combined 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.
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?
Yes. Results are posted in the registry (first posted 17 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Assessment of Lung Toxicity (Pneumonitis) From Treatment With Nivolumab After SBRT for Early Stage NSCLC (time frame: Six months from final dose of SBRT (2-3 weeks) administered for each patient). 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 NCT03383302, 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 17 Jul 2026.