Stereotactic Body Radiotherapy for the Treatment of OPD

NSCLC Clinical Trial

— HALT  

Official title:

Targeted Therapy With or Without Dose Intensified Radiotherapy for Oligo-progressive Disease in Oncogene-addicted Lung Tumours

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03256981
• Other study ID #: ICR-CTSU/2016/10061
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: November 27, 2017
• Est. completion date: June 30, 2025

Study information

• Verified date: December 2023
• Source: Institute of Cancer Research, United Kingdom
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 Inhibitor (TKI).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 113
• Est. completion date: June 30, 2025
• Est. primary completion date: July 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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 = 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.

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

Exclusion Criteria:

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. 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

4. Co-morbidities considered clinically precluding the safe use of SBRT (as detailed in the HALT radiotherapy planning and delivery guidelines).

5. Any psychological, sociological or geographical issue potentially hampering compliance with the study

6. Pregnancy

Related Conditions & MeSH terms

• NSCLC

Intervention

Radiation:
• SBRT
SBRT dose and fractionation dependent on site of metastasis and proximity to critical normal tissues.

Drug:
• TKI
Continued background TKI alone

Locations

Country	Name	City	State
France	Institut Gustave Roussy	Paris
France	Institut Claudius Régaud	Toulouse
Italy	Policlinico Universitario Campus Bio-Medico	Roma
Italy	Ospedale San Luigi Gonzaga - Universita Di Torino	Torino
Spain	Hospital Clinic Universitari de Barcelona	Barcelona
Spain	Institut Català d'Oncologia	Barcelona
Spain	University Hospital Virgen del Rocio	Seville
Switzerland	Oncology Institute of Southern Switzerland	Bellinzona
Switzerland	Hopital Cantonal Universitaire De Geneve	Geneva
Switzerland	Kantonsspital St. Gallen	St. Gallen
Switzerland	UniversitatsSpital Zurich	Zurich
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	Bristol Haematology and Oncology Centre	Bristol
United Kingdom	Royal Marsden Hospital	Chelsea	London
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Royal Surrey County Hospital	Guildford	Surrey
United Kingdom	Castle Hill Hospital	Hull
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	Guy's Hospital	London
United Kingdom	St Bartholomew's Hospital	London
United Kingdom	University College London Hospital	London
United Kingdom	The Christie Hospital	Manchester
United Kingdom	Nottingham City Hospital	Nottingham
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Weston Park Hospital	Sheffield
United Kingdom	Southampton University Hospital	Southampton
United Kingdom	Royal Marsden Hosital	Sutton	England
United Kingdom	Clatterbridge Cancer Centre	Wirral

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Cancer Research, United Kingdom

Countries where clinical trial is conducted

France,  Italy,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	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	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. Assessed 3-monthly until progression and 6-monthly thereafter (up to 24 months).
Secondary	Overall survival		Time from randomisation until death from any cause. Assessed up to 24 months.
Secondary	Patterns of disease progression identified from CT scans to further document natural history of oncogene-addicted NSCLC		Assessed 3-monthly up to 24 months.
Secondary	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.	Baseline, 8 weeks and 3-monthly intervals during follow-up (a minimum of 6 months).
Secondary	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.	Baseline, 8 weeks and 3-monthly intervals during follow-up (a minimum of 6 months).
Secondary	Quality of Life (EQ-5D-5L)	Assessed using EQ-5D-5L	Baseline, 8 weeks and at the first 3 month visit.
Secondary	Quality of Life (EORTC QLQ-C30)	Assessed using EORTC QLQ-C30	Baseline, 8 weeks and at the first 3 month visit.
Secondary	Measurement of resistant sub-clones in Circulating tumour DNA (ctDNA)		Baseline, 8 weeks post-randomisation and 3-monthly intervals during follow-up (up to 24 months).
Secondary	Time to failure of next line treatment		Time from randomisation to disease progression on next line of active systemic therapy. Assessed up to 24 months.