Stereotactic body radiotherapy for the treatment of OPD
| ISRCTN | ISRCTN53398136 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN53398136 |
| IRAS number | 219505 |
| ClinicalTrials.gov number | NCT03256981 |
| Secondary identifying numbers | CPMS 34870, IRAS 219505 |
- Submission date
- 31/07/2017
- Registration date
- 08/08/2017
- Last edited
- 19/06/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Contact information
Dr Steve Penegar
Public
Public
HALT Trial Manager
The Institute of Cancer Research Clinical Trials and Statistics Unit
15 Cotswold Road
Sutton
SM2 5NG
United Kingdom
| Phone | +44 208 722 4238 |
|---|---|
| halt-icrctsu@icr.ac.uk |
Study information
| Study design | Randomized; Interventional; Design type: Treatment, Radiotherapy |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Targeted therapy with or without dose intensified radiotHerapy for oligo-progressive disease in oncogene-Addicted Lung Tumours |
| Study acronym | HALT |
| Study objectives | Current study hypothesis as of 25/10/2021: The aim of this study is to determine whether in patients with mutation positive advanced NSCLC the use of SBRT to ≤5 sites of oligoprogressive disease (OPD) with continuation of TKI improves progression-free survival (PFS) compared with continuation of TKI alone. Previous study hypothesis: The aim of this study is to determine whether in patients with mutation positive advanced NSCLC the use of SBRT to ≤3 sites of oligoprogressive disease (OPD) with continuation of TKI improves progression-free survival (PFS) compared with continuation of TKI alone. |
| Ethics approval(s) | London – Fulham Research Ethics Committee, 10/07/2017, ref: 17/LO/0980 |
| Health condition(s) or problem(s) studied | Lung cancer |
| Intervention | Current interventions as of 25/10/2021: Eligible participants are randomised to receive either Stereotactic Body Radiotherapy (SBRT) or no SBRT at a ratio of 2:1 (SBRT : no SBRT), with all participants continuing to receive background treatment with TKI therapy as clinically indicated and as per standard care. Participants allocated to TKI (tyrosine kinase inhibitor) alone arm continue on the same background TKI treatment as prior to trial entry. Participants allocated to SBRT and TKI arm receive a dose and fractionation schedule dependent on the metastatic site and proximity to critical normal tissues. Patients continue to receive TKI treatment as prior to trial entry. Repeat SBRT is permissible upon development of subsequent OPD (oligoprogressive disease) lesions dependent on SBRT suitability and total progression lesion number at any one point remaining ≤5. All patients are seen eight weeks post-randomisation, then three monthly in line with routine care. Tumour imaging and toxicity assessment is assessed monthly every 3 months until disease progression. Quality of Life is assessed at baseline, eight weeks and at the first 3-month visit. Research bloods are collected at baseline, after the first SBRT fraction (treatment group), 8 weeks and 3 monthly until change in systemic therapy. Previous interventions: Eligible participants are randomised to receive either Stereotactic Body Radiotherapy (SBRT) or no SBRT at a ratio of 2:1 (SBRT : no SBRT), with all participants continuing to receive background treatment with TKI therapy as clinically indicated and as per standard care. Participants allocated to TKI (tyrosine kinase inhibitor) alone arm continue on the same background TKI treatment as prior to trial entry. Participants allocated to SBRT and TKI arm receive a dose and fractionation schedule dependent on the metastatic site and proximity to critical normal tissues. Patients continue to receive TKI treatment as prior to trial entry. Repeat SBRT is permissible upon the development of subsequent OPD (oligoprogressive disease) lesions dependent on SBRT suitability and total progression lesion number at any one point remaining ≤ 3. All patients are seen eight weeks post-randomisation, then three monthly in line with routine care. Tumour imaging and toxicity assessment is assessed monthly every 3 months until disease progression. Quality of Life is assessed at baseline, 8 weeks and at the first 3-month visit. Research bloods are collected at baseline, after the first SBRT fraction (treatment group), 8 weeks and 3 monthly until change in systemic therapy. |
| Intervention type | Other |
| Primary outcome measure | Current primary outcome measures as of 25/10/2021: Progression-free survival defined as the time from randomisation to the first of one of the following events or death from any cause: 1.1. 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 1.2. New or existing intra-cranial lesions not amenable to radical surgery or SRS 1.3. Development of new extra-cranial lesions or progression of existing extra-cranial lesions not meeting the criteria for SBRT treatment (e.g. size >7 cm) 1.4. Development of >5 new or progressing extra-cranial lesion at any one point in time (i.e. widespread progression) Previous primary outcome measures: Progression-free survival defined as the time from randomisation to the first of one of the following events or death from any cause: 1.1. 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. 1.2. New or existing intra-cranial lesions not amenable to radical surgery or SRS. 1.3. Development of new extra-cranial lesions or progression of existing extra-cranial lesions not meeting the criteria for SBRT treatment (e.g. size >5cm) 1.4. Development of >3 new or progressing extra-cranial lesion at any one point in time (i.e. widespread progression) |
| Secondary outcome measures | Current secondary outcome measures as of 25/10/2021: 1. Time to next line of systemic therapy or palliative care – time from randomisation to change in therapy or referral to palliative care due to clinical progression as determined by the treating physician, or death. 2. Overall survival is measured from the time of randomisation until death from any cause. 3. Patterns of disease progression are identified using CT scans to further document natural history of oncogene-addicted NSCLC at 3 monthly intervals. 4. Radiotherapy toxicities (acute and late) assessed using CTCAE v4.0 (clinician and patient versions where available). Acute events are defined as ≤90 days post SBRT start date (applicable for each subsequent course of SBRT where relevant); late events > 90 days. 5. Quality of Life is assessed using EQ-5D-5L and the EORTC QLQ-C30 at baseline, 8 weeks and at the first 3-month visit. 6. Measurement of resistant sub-clones in ctDNA is from blood samples collected at baseline, 8 weeks post-randomisation and 3-monthly during follow-up. 7. Time to failure of next line treatment is measured from the time of randomisation to disease progression on the next line of active systemic therapy. Previous secondary outcome measures: 1. Time to next line of systemic therapy or palliative care – time from randomisation to change in therapy or referral to palliative care due to clinical progression as determined by the treating physician, or death. 2. Overall survival is measured from the time of randomisation until death from any cause. 3. Patterns of disease progression are identified using CT scans to further document natural history of oncogene-addicted NSCLC at 3 monthly intervals 4. Radiotherapy toxicities (acute and late) assessed using CTCAE v4.0 (clinician and patient versions (where available)) and RTOG. Acute events are defined as ≤ 90 days post SBRT start date (applicable for each subsequent course of SBRT where relevant); late events > 90 days. 5. Quality of Life is assessed using EQ-5D-5L and the EORTC QLQ-C30 at baseline, 8 weeks and at the first 3-month visit 6. Measurement of resistant sub-clones in ctDNA is from blood samples collected at baseline, 8 weeks post-randomisation and 3-monthly during follow-up 7. Time to failure of next line treatment is measured from the time of randomisation to disease progression on the next line of active systemic therapy |
| Overall study start date | 01/01/2017 |
| Completion date | 31/12/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 16 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 110; UK Sample Size: 110 |
| Total final enrolment | 113 |
| Key inclusion criteria | Current inclusion criteria as of 25/10/2021: 1. Male or female, ≥16 years of age 2. Established histological diagnosis of advanced NSCLC, not suitable for radical treatment, with defined actionable mutation receiving targeted TKI therapy 3. Clinical and/or radiologically confirmed response to TKI therapy (assessed locally usually 2-3 months post commencing TKI) 4. 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 MDT and in accordance with the HALT Radiotherapy planning and delivery guidance document. 5. Adequate baseline organ function to allow SBRT to all relevant targets 6. Predicted life expectancy ≥6 months 7. Karnofsky Index ≥60% and ECOG 0-2 8. Provision of written informed consent Previous inclusion criteria: 1. Male or female, ≥16 years of age 2. Established histological diagnosis of advanced NSCLC, not suitable for radical treatment, with defined actionable mutation receiving targeted TKI therapy 3. Clinical and/or radiologically confirmed response to TKI therapy (assessed locally usually 2-3 months post commencing TKI) 4. Confirmed OPD defined as ≤3 extracranial sites of progressive disease. All sites must be visible, imaging defined targets and suitable for treatment with SBRT as determined by the virtual MDT and in accordance with the HALT Radiotherapy planning and delivery guidance document. 5. Adequate baseline organ function to allow SBRT to all relevant targets 6. Predicted life expectancy ≥6 months 7. Karnofsky Index ≥60% and ECOG 0-2 8. Provision of written informed consent |
| Key exclusion criteria | Current exclusion criteria as of 25/10/2021: 1. >5 extracranial sites of progressive disease 2. 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. 3. Prior radiotherapy near the oligoprogressive lesion precluding ablative SBRT 4. Co-morbidities considered clinically to preclude safe use of SBRT e.g. IPF in patients with an oligoprogressive lung lesion, inflammatory bowel disease in patients with an oligoprogressive pelvic lymph node 5. Any psychological, sociological or geographical issue potentially hampering compliance with the study 6. Pregnancy Previous exclusion criteria: 1. >3 extracranial sites of progressive disease 2. Brain metastases not amenable to radical surgery or SRS 3. Prior radiotherapy near the oligoprogressive lesion precluding ablative SBRT 4. Co-morbidities considered clinically to preclude safe use of SBRT e.g. IPF in patients with an oligoprogressive lung lesion, inflammatory bowel disease in patients with an oligoprogressive pelvic lymph node 5. Any psychological, sociological or geographical issue potentially hampering compliance with the study 6. Pregnancy |
| Date of first enrolment | 01/10/2017 |
| Date of final enrolment | 17/07/2023 |
Locations
Countries of recruitment
- England
- France
- Italy
- Spain
- Switzerland
- United Kingdom
Study participating centres
The Royal Marsden Hospital
Downs Road
Sutton
SM2 5PT
United Kingdom
Sutton
SM2 5PT
United Kingdom
The Royal Marsden Hospital
Fulham Road
Chelsea
London
SW3 6JJ
United Kingdom
Chelsea
London
SW3 6JJ
United Kingdom
The Christie Hospital
Wimslow Road
Withington
Manchester
M20 4BX
United Kingdom
Withington
Manchester
M20 4BX
United Kingdom
Weston Park Hospital
Whitham Road
Sheffield
S10 2SJ
United Kingdom
Sheffield
S10 2SJ
United Kingdom
Royal Surrey County Hospital
Egerton Road
Guildford
GU2 7XX
United Kingdom
Guildford
GU2 7XX
United Kingdom
Nottingham City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
Nottingham
NG5 1PB
United Kingdom
St Bartholomew's Hospital
West Smithfield
London
EC1A 7BE
United Kingdom
London
EC1A 7BE
United Kingdom
Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom
Glasgow
G12 0YN
United Kingdom
Guy's Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom
London
SE1 9RT
United Kingdom
Southampton General Hospital
Tremona Road
Southampton
S016 6YD
United Kingdom
Southampton
S016 6YD
United Kingdom
Belfast City Hospital
Lisburn Road
Belfast
BT9 7AB
United Kingdom
Belfast
BT9 7AB
United Kingdom
Clatterbridge Cancer Centre
Clatterbridge Road
Wirral
CH63 4JY
United Kingdom
Wirral
CH63 4JY
United Kingdom
University College London Hospital
250 Euston Road
London
NW1 2PG
United Kingdom
London
NW1 2PG
United Kingdom
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
United Kingdom
Headington
Oxford
OX3 7LE
United Kingdom
Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom
Leicester
LE1 5WW
United Kingdom
Bristol Haematology and Oncology Centre
Horfield Road
Bristol
BS2 8ED
United Kingdom
Bristol
BS2 8ED
United Kingdom
Castle Hill Hospital
Castle Road
Cottingham
HU16 5JQ
United Kingdom
Cottingham
HU16 5JQ
United Kingdom
Western General Hospital
Crewe Road South
Edinburgh
EH4 2XU
United Kingdom
Edinburgh
EH4 2XU
United Kingdom
Institut Claudius Reguad IUCT
1 avenue Irène Joliot-Curie
Toulouse
31059
France
Toulouse
31059
France
UniversitatsSpital Zurich
Ramistrasse 100
Zurich
8091
Switzerland
Zurich
8091
Switzerland
Ospedale San Luigi Gonzaga, Universita Di Torino
10 Regione Gonzole
Torino
10043
Italy
Torino
10043
Italy
Institut Català d’Oncologia
Hospital Duran i Reynals
Avinguda de la Gran Via de l’Hospitalet, 199-203
Barcelona
08908
Spain
Avinguda de la Gran Via de l’Hospitalet, 199-203
Barcelona
08908
Spain
Hospital Clinic Universitari de Barcelona
Carrer de Villarroel 170
Barcelona
08036
Spain
Barcelona
08036
Spain
University Hospital Virgen del Rocio
Av. Manuel Siurot
Seville
41013
Spain
Seville
41013
Spain
Institut Gustave Roussy
114 Rue Edouard Vaillant
Villejuif
Paris
94800
France
Villejuif
Paris
94800
France
Policlinico Universitario Campus Bio-Medico
Via Alvaro del Portillo
200
Rome
00128
Italy
200
Rome
00128
Italy
Addenbrookes
Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Sponsor information
Institute of Cancer Research
Research organisation
Research organisation
Royal Cancer Hospital
237 Fulham Road
London
SW3 6JB
United Kingdom
| Phone | +44 208 722 4554 |
|---|---|
| halt-icrctsu@icr.ac.uk | |
"ROR" |
https://ror.org/043jzw605 |
Funders
Funder type
Charity
Cancer Research UK
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The main trial results will be published in a peer-reviewed journal, on behalf of all collaborators. Study results will aim to be published within 1 year after trial ends. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from halt-icrctsu@icr.ac.uk |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
19/06/2025: The overall study end date was changed from 30/06/2025 to 31/12/2025. Total final enrolment added.
07/04/2025: The applicant stated that the record was up to date.
18/03/2024: The following changes were made to the trial record:
1. The overall study end date was changed from 31/03/2024 to 30/06/2025.
2. The intention to publish date was changed from 31/12/2024 to 31/12/2025.
19/09/2023: The following changes were made to the study record:
1. The recruitment end date was changed from 30/06/2023 to 17/07/2023.
2. The overall study end date was changed from 30/09/2023 to 31/03/2024.
3. The intention to publish date was changed from 31/03/2024 to 31/12/2024.
4. Total final enrolment and IRAS number added.
5. Contact details updated.
16/03/2023: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/03/2023 to 30/06/2023.
2. The overall end date was changed from 30/06/2023 to 30/09/2023.
3. The trial participating centre 'Addenbrooke's Hospital' was added.
29/09/2022: The following changes were made to the trial record:
1. The overall end date was changed from 31/03/2023 to 30/06/2023.
2. The recruitment end date was changed from 30/09/2022 to 31/03/2023.
26/10/2021: Contact details updated.
25/10/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 30/09/2020 to 30/09/2022.
2. The overall trial end date was changed from 30/09/2021 to 31/03/2023.
3. The study hypothesis, interventions, primary and secondary outcome measures, inclusion and exclusion criteria were updated.
4. Trial website added.
5. France, Italy, Spain and Switzerland were added to the countries of recruitment.
6. The following trial participating centres were added: The Christie Hospital, Weston Park Hospital, Royal Surrey County Hospital, Nottingham City Hospital, St Bartholomew's Hospital, Beatson West of Scotland Cancer Centre, Guy's Hospital, Southampton General Hospital, Belfast City Hospital, Clatterbridge Cancer Centre, University College London Hospital, Churchill Hospital, Leicester Royal Infirmary, Bristol Haematology and Oncology Centre, Castle Hill Hospital, Western General Hospital, Institut Claudius Reguad IUCT, UniversitatsSpital Zurich, Ospedale San Luigi Gonzaga, Universita Di Torino, Institut Català d’Oncologia, Hospital Clinic Universitari de Barcelona, University Hospital Virgen del Rocio, Institut Gustave Roussy, Policlinico Universitario Campus Bio-Medico.
7. The intention to publish date was changed from 30/09/2022 to 31/03/2024.
20/09/2021: Internal review.
13/07/2020: The trial contact details have been made publicly visible.
21/06/2019: ClinicalTrials.gov number added.
03/04/2019: The condition has been changed from "Specialty: Cancer, Primary sub-specialty: Lung Cancer; UKCRC code/ Disease: Cancer/ Malignant neoplasms of respiratory and intrathoracic organs" to "Lung Cancer" following a request from the NIHR.
05/03/2019: Cancer Research UK lay summary link added to plain English summary field.
07/06/2018: Internal review.
14/05/2018: Internal review.
16/01/2018: Internal review.
16/10/2017: Internal review.
22/09/2017: Internal review
