A Phase 2 interventional study of Image-Guided Stereotactic Ablative Radiotherapy (IG-SABR) in NSCLC/Oligometastatic Cancer (Single Lung Lesion), sponsored by Cancer Trials Ireland. Recruiting at 2 sites in Ireland. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-05-02.
Sponsored by Cancer Trials Ireland · Phase 2, Interventional, and Treatment
This is a phase II, non-randomised study examining the safety of treating high risk centrally located non-small cell lung cancer (NSCLC) tumours and single pulmonary oligometastatic lesions using radiation therapy (RT), for patients whose disease is inoperable. The method of delivering the RT in this study is image guided stereotactic ablative radiation therapy (IG-SABR). This method involves using imaging to ensure the radiation is being delivered to the correct location within the body and using higher than normal doses per treatment (fraction) to treat the lung cancer (NSCLC)/oligometastatic lung lesion. This study aims to determine its safety by looking at the number and severity of side effects. This study will deliver 8 treatments/fractions of RT with 7.5 Gy delivered in each fraction. To be eligible for this study the initial treatment plan for the patient must be shown to not fulfil certain criteria relating to doses to the tumour and surrounding normal tissue. This study has its own study specific criteria which must be adhered to. Translational sub-studies (optional) are open to patients in participating centres only. Patients will have the option to consent to participating in both translational studies or to neither.
This study is a phase II non-randomised, multi-centre, single arm trial of image-guided (IG)-SABR for patients with high-risk centrally located T1-T4 lung tumours (NSCLC) or a single pulmonary oligometastatic lesions. Treatment will consist of IG-SABR using a total of 8 fractions of 7.5 Gy per fraction adhering to organ at risk dose-volume histogram constraints allowing a minimum dose coverage of 75% to 95% of the planning target volume (PTV) coverage, and a minimum dose of 87% to 99% of the gross tumour volume (GTV), using dose intensity modulation.
The primary aim of the study is to determine the safety of the 8 x 7.5 Gy treatment regimen on the basis of the rate of ≥ Grade 3 treatment related toxicity using NCI CTCAE V5, in patients with medically inoperable early stage, ultracentrally located lung tumours. This is defined by central tumours which are not fulfilling the conservative hybrid DVCs of the LungTech (Adebahr et al., 2015), RTOG 0813 (Bezjak et al., 2015) studies and current UK consortium guidelines with full dose coverage, but which subsequently meet SOURCE DVC's with potentially reduced dose coverage. To remain in line with international practice, the SOURCE Lung protocol was amended to reduce near maximum dose constraints to 0.1cc for OARs (Diez et al. 2022). Toxicities occurring between start of treatment and one-year from the end of treatment, which are possibly, probably or definitely related to radiotherapy will be assessed.
A total of 60 evaluable patients will be required for the study. The sample size was calculated using continuous monitoring for toxicity, up to one year post RT, using a Pocock-type boundary. Accrual will be halted if excessive numbers of ≥ Grade 3 TxR-AEs are seen. The regime will not be considered to be safe if >25% of evaluable patients experience a ≥ Grade 3 treatment-related adverse event (TxR-AE) by the end of 1-year post-RT. This study will be considered adequately safe if ≤ 25% of evaluable patients experience ≥ Grade 3 TxR-AE by the end of 1 year post-RT.
The enrolment period is expected to be 6 years.
Toxicity assessments will be carried out weekly during radiotherapy (RT), at 2, 4 and 8-weeks post-treatment and at 3, 6, 9, 12, 18, 24 months post treatment and annually thereafter to 5 years post treatment.
Translational Sub-Study 1 (Raman spectroscopic analysis) - Primary aim is to undertake biomarker discovery using label-free Raman spectroscopy coupled with multivariate statistical methods to identify spectral biomarkers that could:
Translational Sub-Study 2 (Proteomic analysis) - Primary aim is to use proteomic analysis of sequential blood samples before, during and after treatment to detect changes in protein expression profiles that may predict outcome and identify prognostic biochemical markers of early toxicity.
7,620 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,838 are open to participants now.
This study's planned enrollment of 68 is close to the median of 62 across 6,019 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.
Browse Carcinoma, Non-Small-Cell Lung studies →Cancer Trials Ireland is the lead sponsor of 71 studies on the registry; 8 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Histological diagnosis ( or cytology) or radiological diagnosis (PET-positive FDG-avid tumour which has only one lesion to be treated for the purpose of the study / CT-based diagnosis for non FDG-avid tumour) which requires local ablative therapy per Multi-Disciplinary Team (MDT) recommendations) of either:
(i) Primary NSCLC (Squamous Cell Carcinoma (SCC), Adenocarcinoma, Large Cell) OR (ii) Single pulmonary oligometastatic lesion to be treated for the purpose of the study
Patients with central lung tumours/lesions whose radiotherapy plan meets the following criteria:
(i) OAR eligibility constraints are initially exceeded when full PTV coverage is met; (ii) subsequently meets the CTRIAL-IE 18-33 SOURCE OAR Lung constraints and meets CTRIAL-IE 18-33 SOURCE Lung minimum constraints
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Treatment will be delivered via image-guided (IG)-SABR in 8 fractions of 7.5Gy. OAR constraints must be respected but minimum dose coverage of 75% to 95% of the PTV will be allowed and minimum dose of 75% to 99% of the GTV will be allowed. The minimums are chosen to represent at least an equivalent BED to the RT standard fractionation of 55 Gy in 20 fractions based on actual treatment dose of 7.5Gy in 8 fractions. A total of 60 evaluable patients will be required for the study. The sample size was calculated using continuous monitoring for toxicity, up to one year post RT, using a Pocock-type boundary. Accrual will be halted if excessive numbers of ≥ Grade 3 TxR-AEs are seen. The regime will not be considered to be safe if \>25% of evaluable patients experience a ≥ Grade 3 treatment-related adverse event (TxR-AE) by the end of 1-year post-RT. This study will be considered adequately safe if ≤ 25% of evaluable patients experience ≥ Grade 3 TxR-AE by the end of 1 year post-RT.
Radiation: Image-Guided Stereotactic Ablative Radiotherapy (IG-SABR)
Image-Guided Stereotactic Ablative Radiotherapy (IG-SABR) delivered in 8 fractions of 7.5 Gy. OAR constraints must be respected but a minimum dose coverage to 95% of the PTV will be allowed down to 75% and a minimum dose to 99% of the GTV allowed at 75%. Respiratory monitoring/active respiratory management will be used. Plans will be created and delivered using photon beams with energies between 6-10 MV.
The rate of ≥ Grade 3 treatment-related toxicities occurring between start of treatment and one-year from the end of treatment using NCI CTCAE V5
The rates of ≥ Grade 3 treatment-related adverse events (TxR-AEs) will be calculated as the proportion of evaluable patients (along with the 95% CI) who have any \>= Grade 3 treatment-related adverse event occurring between the start of RT and one year post-RT, among the total evaluable patients. These rates will be reported (for applicable patients) by T stage (T1 versus T2 versus T3 versus T4 or combined T stages). The NCI Common Terminology Criteria for Adverse Events (CTCAE Version 5.0) for scoring the treatment-related adverse events will be used. The following will be reported at the time of primary endpoint analysis * Tabulation of all cases entered, and any patients excluded from the analysis with reasons for exclusion; * Distribution of important prognostic baseline and other pre-treatment variables; * Frequency and severity of adverse events; * Compliance rates of treatment delivery with respect to the protocol prescription
Time frame: From start of treatment to 1 year post treatment
Estimate time to locoregional recurrence/progression, locoregional recurrence-free survival (LRFS), disease-free survival (DFS) and metastasis-free survival rates / further metastasis-free survival rates (for patients with an oligometastatic lesion).
The Kaplan-Meier method will be used to estimate time to locoregional recurrence; the cumulative proportion surviving without local recurrence at 1- year, 3-years and 5-years; DFS; metastasis-free survival for patients with primary NSCLC; further metastasis-free survival for patients with an oligometastatic lesion. These efficacy endpoints will be expressed as median survival with 95% confidence interval.
Time frame: Up to 5 years post treatment
Estimates of 1-year, 3-year and 5-year overall survival rates
The Kaplan-Meier method will be used to estimate time the cumulative proportion surviving (overall survival) at 1-year, 3-years and 5-years. Overall survival will be measured from date of registration/ enrolment. Patients alive and free of event at the time of analysis and patients lost to follow-up will be censored at the last available assessment. The event for overall survival is a death due to any cause. The primary time-point of interest is 12 months.
Time frame: Up to 5 years post treatment
Post treatment response and outcomes using PET and CT at 3, 6, 9, 12,18, 24, 36, 48 and 60 months post-RT
Only patients who received the prescribed RT dose and who are alive at the specified CT TA timepoints during follow up will be evaluated for tumour response and included in the analysis of tumour response rates. Whole body FDG-PET-CT scan will be done within 18 weeks prior to registration (may be conducted 18-22 weeks prior to registration for some patients, if the patient has had a CT TA within 18 weeks prior to registration), at 6 months and as clinically indicated post-SABR based on review of CT-TA scans.
Time frame: Up to 60 months (5 years) post treatment
Acute toxicity profiles on treatment to 3 months post treatment
Acute toxicity rates will be calculated, summarised and presented in tabular format with proportions plus 95% confidence intervals where appropriate.
Time frame: Up to 3 months post treatment
Late toxicity profiles to 5 years post treatment
Late toxicity rates will be calculated, summarised and presented in tabular format with proportions plus 95% confidence intervals where appropriate.
Time frame: Up to 5 years post treatment
Time to onset of acute and late ≥ Grade 2 and ≥ Grade 3 toxicities
Time to event will be measured for toxicities (which are related to trial treatment) from treatment start date. Patients alive and free of event at the time of analysis and patients lost to follow-up will be censored at the last available assessment. The primary time-point of interest is 12 months.
Time frame: Up to 5 years post treatment
Changes in domain-specific Quality of Life (QoL) outcomes at 6 months post treatment compared with outcomes at baseline using the EORTC QLQ C30 (and EORTC QLQ LC13)
The mean and standard deviation (SD) of the domain-specific EORTC QLQ C30 and EORTC QLQ LC13 scores at baseline and 6 months post treatment will be reported. Scoring will be in line with the published guidelines and will use the QLQ-C30 summary score (excluding financial difficulties and global QOL). The scales are from 1(Not at all) to 4(Very Much) with 1 being the best outcome, and from 1(Very poor) to 7(excellent) with 7 being the best outcome. The proportion of patients who report 'quite a bit' and/or 'very much' for each domain or measure will be reported. Changes in scores over time for each patient will be calculated by subtracting the results at baseline from 6 month results. The mean and SD of the changes will be reported. A Wilcoxon signed rank test will be used to compare differences from baseline. The number of patients who had a clinically meaningful change in QoL as identified by the method recommended by the EORTC QoL Group at the time of analysis will also be reported.
Time frame: From baseline up to 6 months post treatment
Changes in symptom-specific Quality of Life (QoL) outcomes at 6 months post treatment compared with outcomes at baseline using the EORTC QLQ C30 (and EORTC QLQ LC13)
The mean and standard deviation (SD) of the symptom-specific EORTC QLQ C30 and EORTC QLQ LC13 scores at baseline and 6 months post treatment will be reported. Scoring will be in line with the published guidelines and will use the QLQ-C30 summary score (excluding financial difficulties and global QOL). The scales are from 1(Not at all) to 4(Very Much) with 1 being the best outcome and from 1(Very poor) to 7(excellent) with 7 being the best outcome. The proportion of patients who report 'quite a bit' and/or 'very much' for each domain or measure will be reported. Changes in scores over time for each patient will be calculated by subtracting the results at baseline from 6 month results. The mean and SD of the changes will be reported. A Wilcoxon signed rank test will be used to compare differences from baseline. The number of patients who had a clinically meaningful change in QoL as identified by the method recommended by the EORTC QoL Group at the time of analysis will also be reported.
Time frame: From baseline up to 6 months post treatment
Treatment tolerability and feasibility rates based on compliance with prescription and the number of treatment reductions/withdrawals.
Treatment tolerability and feasibility will be measured in terms of the compliance rate for treatment delivery with respect to the protocol prescription and the number of treatment reductions and treatment withdrawals
Time frame: Through study treatment, an average of 3 weeks
Pulmonary function changes
The change in pulmonary function post-treatment will be analysed by calculating the differences in measurements (of PFTs) from baseline to the 12-month follow-up. The descriptive statistics of changes of FEV1 and diffusion capacity before and after treatment will be reported (at least mean, standard deviation, median, and range).
Time frame: Up to 12 months post treatment
Changes in overall Quality of Life (QoL) outcomes at 6 months post treatment compared with outcomes at baseline using the European Organisation for Research and Treatment of Cancer QoL Questionnaire (EORTC QLQ) C30 and EORTC QLQ Lung Cancer (LC)13
The mean and standard deviation (SD) of the overall EORTC QLQ C30 and EORTC QLQ LC13 scores at baseline and 6 months post treatment will be reported. Scoring will be in line with the published guidelines and will use the QLQ-C30 summary score (excluding financial difficulties and global QOL). The scales are from 1 (Not at all) to 4 (Very Much) with 1 being the best outcome, and from 1 (Very poor) to 7 (excellent) with 7 being the best outcome. The proportion of patients who report 'quite a bit' and/or 'very much' for each domain or measure will be reported. Changes in scores over time for each patient will be calculated by subtracting the results at baseline from 6month results. The mean and SD of the changes will be reported. A Wilcoxon signed rank test will be used to compare differences from baseline. The number of patients who had a clinically meaningful change in QoL as identified by the method recommended by the EORTC QoL Group at the time of analysis will also be reported.
Time frame: From baseline up to 6 months post treatment
Develop a platform for prediction and monitoring of treatment response/toxicities using Raman spectra of the cellular and plasma fraction of the patient blood. (Sub-Study 1)
Raman spectra will be recorded from both lymphocytes and plasma to produce a library of spectral measurements in patients pre- and post-treatment. Advanced multivariate and machine learning methodologies will be used to develop a platform for prediction and monitoring of treatment response/toxicities using Raman spectra of the cellular and plasma fraction of the patient blood.
Time frame: 9 months follow-up
Identify blood biomarkers as indicators for toxicity/relapse and the development of a panel of predictive/prognostic biomarkers. (Sub-Study 2)
To detect changes in protein expression profiles that may predict outcome and identify prognostic biochemical markers of early toxicity
Time frame: 9 months follow up
Plan to share: Undecided
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Started Dec 2020 (actual). Primary completion is estimated for Feb 2028, 86 months after the start.
Of 730 non-industry phase 2 interventional studies under Carcinoma, Non-Small-Cell Lung, half reached primary completion within 56 months of starting (the median), counting those still running; a quarter within 36 and three quarters within 84. This study's planned 86 months is above that.
Counting every sponsor, half of 1,047 studies reached it within 48 months; a quarter within 30 and three quarters within 76.
How these figures are worked out, and which studies are left out of them.
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