Condition category
Cancer
Date applied
31/07/2017
Date assigned
08/08/2017
Last edited
09/08/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Lay summary under review with external organisation

Trial website

Contact information

Type

Public

Primary contact

Dr Deborah Alawo

ORCID ID

Contact details

HALT Trial Manager
The Institute of Cancer Research Clinical Trials and Statistics Unit
15 Cotswold Road
Sutton
SM2 5NG
United Kingdom

Additional identifiers

EudraCT number

N/A

ClinicalTrials.gov number

Protocol/serial number

34870

Study information

Scientific title

Targeted therapy with or without dose intensified radiotHerapy for oligo-progressive disease in oncogene-Addicted Lung Tumours

Acronym

HALT

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

London – Fulham Research Ethics Committee, 10/07/2017, ref: 17/LO/0980

Study design

Randomised; Interventional; Design type: Treatment, Radiotherapy

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Cancer, Primary sub-specialty: Lung Cancer; UKCRC code/ Disease: Cancer/ Malignant neoplasms of respiratory and intrathoracic organs

Intervention

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 ≤ 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 ever three months until disease progression. Quality of Life is assessed at baseline, eight weeks and at the first three month visit. Research bloods is collected at baseline, after the first SBRT fraction (treatment group), eight weeks and three monthly until change in systemic therapy.

Intervention type

Other

Phase

Drug names

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

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, eight weeks and at the first three month visit
6. Measurement of resistant sub-clones in ctDNA is from blood samples collected at baseline, eight weeks post-randomisation and three-monthly during follow-up
7. Time to failure of next line treatment is measured from the time of randomisation to disease progression on next line of active systemic therapy

Overall trial start date

01/01/2017

Overall trial end date

30/09/2021

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 110; UK Sample Size: 110

Participant 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

Recruitment start date

01/10/2017

Recruitment end date

30/09/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

The Royal Marsden Hospital
Downs Road
Sutton
SM2 5PT
United Kingdom

Trial participating centre

The Royal Marsden Hospital
Fulham Road Chelsea
London
SW3 6JJ
United Kingdom

Sponsor information

Organisation

Institute of Cancer Research

Sponsor details

Royal Cancer Hospital
237 Fulham Road
London
SW3 6JB
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Cancer Research UK

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

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 statement:
The datasets generated during and/or analysed during the current study are/will be available upon request from halt-icrctsu@icr.ac.uk

Intention to publish date

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes