NSCLCPhase 2/3HALTNCT03256981
Stereotactic Body Radiotherapy for the Treatment of OPD
A Phase 2/3 study testing SBRT and TKI in people with NSCLC, run by Institute of Cancer Research, United Kingdom at 29 sites in 5 countries.
Trial summary
HALT is a phase II, randomised multi-centre study with integrated seamless continuation to phase III trial following acceptable safety and feasibility assessment. HALT aims to recruit 110 patients with mutation positive advanced NSCLC with oligoprogressive disease (OPD) following initial response to a Tyrosine Kinase… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- NSCLC
- What is being tested?
- SBRT and TKI
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 113 participants
- Where
- 29 sitesin 5 countries
- Study dates
- 27 Nov 2017to 30 Jun 2027
- Phase
- Phase 2/3
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female, ≥ 16 years of age
- Established histological diagnosis of advanced NSCLC, not suitable for radical treatment, with defined actionable mutation receiving targeted TKI therapy
- Clinical and/or radiologically confirmed response to TKI therapy (assessed locally usually 2-3 months post commencing TKI)
- Confirmed OPD defined as ≤ 5 extracranial sites of progressive disease. All sites must be visible, imaging defined targets and suitable for treatment with SBRT as determined by the virtual multi-disciplinary team (MDT) and in accordance with the HALT Radiotherapy planning and delivery guidance document.
- Adequate baseline organ function to allow SBRT to all relevant targets
- Predicted life expectancy ≥ 6 months
- Karnofsky Index ≥ 60% and ECOG 0-2
- Provision of written informed consent
Who cannot join
- > 5 extracranial sites of progressive disease
- Progressing or newly diagnosed brain metastases identified at the time of trial entry, not amenable to radical surgery or SRS. Previously treated brain metastases (i.e palliative radiotherapy or systemic therapy) which have remained clinically and radiologically stable for ≥ 6 months are permissible.
- Prior radiotherapy near the oligoprogressive lesion precluding ablative SBRT. Suitability of lesions for ablative SBRT as part of the trial defined in section 4.1 of this document and will be determined by the HALT virtual MDT
- Co-morbidities considered clinically precluding the safe use of SBRT (as detailed in the HALT radiotherapy planning and delivery guidelines).
- Any psychological, sociological or geographical issue potentially hampering compliance with the study
- Pregnancy
Trial locations and contacts
29 sites in 5 countries.
29 sites in 5 countries
United Kingdom18 sites
Belfast City Hospital
Belfast, BT9 7AB
Bristol Haematology and Oncology Centre
Bristol, BS2 8ED
Royal Marsden Hospital
Chelsea, London, SW3 6JJ
Western General Hospital
Edinburgh, EH4 2XU
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN
Royal Surrey County Hospital
Guildford, Surrey, GU2 7XX
Castle Hill Hospital
Hull, HU16 5JQ
Leicester Royal Infirmary
Leicester, LE1 5WW
St Bartholomew's Hospital
London, EC1A 7BE
University College London Hospital
London, NW1 2PG
Guy's Hospital
London, SE1 9RT
The Christie Hospital
Manchester, M20 4BX
Clatterbridge Cancer Centre
Metropolitan Borough of Wirral, CH63 4JY
Nottingham City Hospital
Nottingham, NG5 1PB
Churchill Hospital
Oxford, OX3 7LE
Weston Park Hospital
Sheffield, S10 2SJ
Southampton University Hospital
Southampton, SO16 6YD
Royal Marsden Hosital
Sutton, England, SM2 5PT
Switzerland4 sites
Oncology Institute of Southern Switzerland
Bellinzona, 6500
Hopital Cantonal Universitaire De Geneve
Geneva
Kantonsspital St. Gallen
Sankt Gallen, 9007
UniversitatsSpital Zurich
Zurich, 8091
Spain3 sites
Hospital Clinic Universitari de Barcelona
Barcelona, 08036
Institut Català d'Oncologia
Barcelona, 08908
University Hospital Virgen del Rocio
Seville, 41013
France2 sites
Institut Gustave Roussy
Paris, 94800
Institut Claudius Régaud
Toulouse, 31059
Italy2 sites
Policlinico Universitario Campus Bio-Medico
Roma, 00128
Ospedale San Luigi Gonzaga - Universita Di Torino
Torino, 10043
About this study
Official title: Targeted Therapy With or Without Dose Intensified Radiotherapy for Oligo-progressive Disease in Oncogene-addicted Lung Tumours
HALT is a phase II, randomised multi-centre study with integrated seamless continuation to phase III trial following acceptable safety and feasibility assessment.
HALT aims to recruit 110 patients with mutation positive advanced NSCLC with oligoprogressive disease (OPD) following initial response to a Tyrosine Kinase Inhibitor (TKI).
Read the detailed description
Eligible patients will be randomised to receive either SBRT or no SBRT at a ratio of 2:1 (SBRT : no SBRT), with all patients continuing to receive background treatment with TKI therapy as clinically indicated and as per standard care. Patients randomised to receive SBRT will receive a dose and fractionation schedule dependent on OPD lesion site and proximity to critical normal tissues. All patients will be seen 8 weeks post randomisation, then 3 monthly in line with routine care.
HALT aims to assess whether in patients with mutation positive advanced NSCLC the use of SBRT to ≤ 3 sites of OPD with continuation of TKI improves progression-free survival (PFS) compared with continuation of TKI alone.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SBRTRadiation
Also called Stereotactic body radiotherapy, SABR
SBRT dose and fractionation dependent on site of metastasis and proximity to critical normal tissues.
TKIDrug
Also called Tyrosine Kinase Inhibitor
Continued background TKI alone
| Study group | Role | What they receive |
|---|---|---|
| SBRT and continued TKI therapy | Experimental | Patients will continue to receive background TKI treatment as prior to trial entry.
Simultaneous administration (SBRT \& TKI) or break in TKI during SBRT will be by centre preference and determined prior to commencing recruitment.
Repeat SBRT will be permissible upon development of subsequent OPD lesions dependent on SBRT suitability and total progression lesion number at any one point remaining ≤ 5. Receives: Radiation: SBRT |
| Continued TKI therapy alone | Active comparator | Continuation on the same background TKI treatment as prior to trial entry Receives: Drug: TKI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
The primary outcome measure is progression free survival defined as the time from randomisation to the first of one of the following events or death from any cause:
- Clinically symptomatic progression requiring palliative tumour-specific oncological intervention (e.g. change in systemic therapy or localised non-SBRT radiotherapy) as determined by the treating physician.
- New or existing intra-cranial lesions not amenable to radical surgery or Stereotactic radiosurgery (SRS).
- Development of new extra-cranial lesions or progression of existing extra-cranial lesions not meeting the criteria for
- SBRT treatment (e.g. size >7cm)
- Development of >5 new or progressing extra-cranial lesion at any one point in time (i.e. widespread progression)
Measured: Time from randomisation to the first of one of the above events or death. Assessed 8 weeks post-randomisation and 3-monthly thereafter (up to 24 months)
Secondary outcomes (9)
Time to next line of systemic therapy or palliative care
Measured: Time from randomisation to change in therapy or referral to palliative care due to clinical progression as determined by the treating physician, or death. Assessed 3-monthly until progression and 6-monthly thereafter (up to 24 months).
Overall survival
Measured: Time from randomisation until death from any cause. Assessed up to 24 months.
Patterns of disease progression identified from CT scans to further document natural history of oncogene-addicted NSCLC
Measured: Assessed 3-monthly up to 24 months.
Radiotherapy toxicities (acute events)
Acute events are defined as ≤ 90 days post SBRT start date (applicable for each subsequent course of SBRT where relevant) assessed using CTCAE v4.0.
Measured: Baseline, 8 weeks and 3-monthly intervals during follow-up (a minimum of 6 months).
Radiotherapy toxicities (late events)
Late events are defined as > 90 days post SBRT start date (applicable for each subsequent course of SBRT where relevant) assessed using CTCAE v4.0.
Measured: Baseline, 8 weeks and 3-monthly intervals during follow-up (a minimum of 6 months).
Quality of Life (EQ-5D-5L)
Assessed using EQ-5D-5L
Measured: Baseline, 8 weeks and at the first 3 month visit.
Quality of Life (EORTC QLQ-C30)
Assessed using EORTC QLQ-C30
Measured: Baseline, 8 weeks and at the first 3 month visit.
Measurement of resistant sub-clones in Circulating tumour DNA (ctDNA)
Measured: Baseline, 8 weeks post-randomisation and 3-monthly intervals during follow-up (up to 24 months).
Time to failure of next line treatment
Measured: Time from randomisation to disease progression on next line of active systemic therapy. Assessed up to 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2017
- Study start27 Nov 2017
- Primary completion17 Jul 2023
- Study completion30 Jun 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 NSCLCStudies of the same condition, open and under way.
- More trials run by Institute of Cancer Research, United KingdomThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 113 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Cancer Research, United Kingdom
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Fiona McDonald, MD, Principal investigator, Royal Marsden NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03256981
- Sponsor's protocol ID
- ICR-CTSU/2016/10061
- Acronym
- HALT
- Status last verified
- Nov 2026
- First submitted
- 10 Aug 2017
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Lee J, Koom WS, Byun HK, Yang G, Kim MS, Park EJ, Ahn JB, Beom SH, Kim HS, Shin SJ, Kim K, Chang JS. Metastasis-Directed Radiotherapy for Oligoprogressive or Oligopersistent Metastatic Colorectal Cancer. Clin Colorectal Cancer. 2022 Jun;21(2):e78-e86. doi: 10.1016/j.clcc.2021.10.009. Epub 2021 Nov 18.
PubMed 34903471
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeted Therapy With or Without Dose Intensified Radiotherapy for Oligo-progressive Disease in Oncogene-addicted Lung Tumours
- ClinicalTrials.gov ID
- NCT03256981
- Acronym / sponsor ID
- HALT / ICR-CTSU/2016/10061
- Conditions
- NSCLC
- Keywords
- SBRT, Oligoprogressive disease, NSCLC, TKI
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 113 participants (actual)
- Lead sponsor
- Institute of Cancer Research, United KingdomUniversity, hospital or other
- Study start
- 27 Nov 2017 (actual)
- Primary completion
- 17 Jul 2023 (actual)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 22 Aug 2017 (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.
HALT is a phase II, randomised multi-centre study with integrated seamless continuation to phase III trial following acceptable safety and feasibility assessment.
HALT aims to recruit 110 patients with mutation positive advanced NSCLC with oligoprogressive disease (OPD) following initial response to a Tyrosine Kinase Inhibitor (TKI).
Detailed description
Eligible patients will be randomised to receive either SBRT or no SBRT at a ratio of 2:1 (SBRT : no SBRT), with all patients continuing to receive background treatment with TKI therapy as clinically indicated and as per standard care. Patients randomised to receive SBRT will receive a dose and fractionation schedule dependent on OPD lesion site and proximity to critical normal tissues. All patients will be seen 8 weeks post randomisation, then 3 monthly in line with routine care.
HALT aims to assess whether in patients with mutation positive advanced NSCLC the use of SBRT to ≤ 3 sites of OPD with continuation of TKI improves progression-free survival (PFS) compared with continuation of TKI alone.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SBRT and continued TKI therapy | Experimental | Radiation: SBRTPatients will continue to receive background TKI treatment as prior to trial entry. Simultaneous administration (SBRT \& TKI) or break in TKI during SBRT will be by centre preference and determined prior to commencing recruitment. Repeat SBRT will be permissible upon development of subsequent OPD lesions dependent on SBRT suitability and total progression lesion number at any one point remaining ≤ 5. |
| Continued TKI therapy alone | Active comparator | Drug: TKIContinuation on the same background TKI treatment as prior to trial entry |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female, ≥ 16 years of age
- Established histological diagnosis of advanced NSCLC, not suitable for radical treatment, with defined actionable mutation receiving targeted TKI therapy
- Clinical and/or radiologically confirmed response to TKI therapy (assessed locally usually 2-3 months post commencing TKI)
- Confirmed OPD defined as ≤ 5 extracranial sites of progressive disease. All sites must be visible, imaging defined targets and suitable for treatment with SBRT as determined by the virtual multi-disciplinary team (MDT) and in accordance with the HALT Radiotherapy planning and delivery guidance document.
- Adequate baseline organ function to allow SBRT to all relevant targets
Key exclusion criteria (6 listed)
- > 5 extracranial sites of progressive disease
- Progressing or newly diagnosed brain metastases identified at the time of trial entry, not amenable to radical surgery or SRS. Previously treated brain metastases (i.e palliative radiotherapy or systemic therapy) which have remained clinically and radiologically stable for ≥ 6 months are permissible.
- Prior radiotherapy near the oligoprogressive lesion precluding ablative SBRT. Suitability of lesions for ablative SBRT as part of the trial defined in section 4.1 of this document and will be determined by the HALT virtual MDT
- Co-morbidities considered clinically precluding the safe use of SBRT (as detailed in the HALT radiotherapy planning and delivery guidelines).
- Any psychological, sociological or geographical issue potentially hampering compliance with the study
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 |
|---|---|---|
| SBRTAlso: Stereotactic body radiotherapy, SABRSBRT dose and fractionation dependent on site of metastasis and proximity to critical normal tissues. | Radiation | SBRT and continued TKI therapy |
| TKIAlso: Tyrosine Kinase InhibitorContinued background TKI alone | Drug | Continued TKI therapy alone |
Primary outcome
Progression free survival
Time frame: Time from randomisation to the first of one of the above events or death. Assessed 8 weeks post-randomisation and 3-monthly thereafter (up to 24 months)
The primary outcome measure is progression free survival defined as the time from randomisation to the first of one of the following events or death from any cause: * Clinically symptomatic progression requiring palliative tumour-specific oncological intervention (e.g. change in systemic therapy or localised non-SBRT radiotherapy) as determined by the treating physician. * New or existing intra-cranial lesions not amenable to radical surgery or Stereotactic radiosurgery (SRS). * Development of new extra-cranial lesions or progression of existing extra-cranial lesions not meeting the criteria for * SBRT treatment (e.g. size >7cm) * Development of >5 new or progressing extra-cranial lesion at any one point in time (i.e. widespread progression)
9 secondary outcomes
Time to next line of systemic therapy or palliative care
Time frame: Time from randomisation to change in therapy or referral to palliative care due to clinical progression as determined by the treating physician, or death. Assessed 3-monthly until progression and 6-monthly thereafter (up to 24 months).
Overall survival
Time frame: Time from randomisation until death from any cause. Assessed up to 24 months.
Patterns of disease progression identified from CT scans to further document natural history of oncogene-addicted NSCLC
Time frame: Assessed 3-monthly up to 24 months.
Radiotherapy toxicities (acute events)
Time frame: Baseline, 8 weeks and 3-monthly intervals during follow-up (a minimum of 6 months).
Radiotherapy toxicities (late events)
Time frame: Baseline, 8 weeks and 3-monthly intervals during follow-up (a minimum of 6 months).
Quality of Life (EQ-5D-5L)
Time frame: Baseline, 8 weeks and at the first 3 month visit.
Quality of Life (EORTC QLQ-C30)
Time frame: Baseline, 8 weeks and at the first 3 month visit.
Measurement of resistant sub-clones in Circulating tumour DNA (ctDNA)
Time frame: Baseline, 8 weeks post-randomisation and 3-monthly intervals during follow-up (up to 24 months).
Time to failure of next line treatment
Time frame: Time from randomisation to disease progression on next line of active systemic therapy. Assessed up to 24 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 5 Nov 2026.
- Derived from this study: PubMed 34903471Lee J, Koom WS, Byun HK, Yang G, Kim MS, Park EJ, Ahn JB, Beom SH, Kim HS, Shin SJ, Kim K, Chang JS. Metastasis-Directed Radiotherapy for Oligoprogressive or Oligopersistent Metastatic Colorectal Cancer. Clin Colorectal Cancer. 2022 Jun;21(2):e78-e86. doi: 10.1016/j.clcc.2021.10.009. Epub 2021 Nov 18.
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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.
Fiona McDonald, MD principal investigator
Royal Marsden NHS Foundation Trust
29 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing SBRT and TKI in people with NSCLC, run by Institute of Cancer Research, United Kingdom at 29 sites in 5 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 8 inclusion and 6 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 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United Kingdom, Switzerland, Spain, France, Italy. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Progression free survival (time frame: Time from randomisation to the first of one of the above events or death. Assessed 8 weeks post-randomisation and 3-monthly thereafter (up to 24 months)). 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 NCT03256981, 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 5 Nov 2026.