Clinical trial NCT03256981: Stereotactic Body Radiotherapy for the Treatment of OPD
Official title: Targeted Therapy With or Without Dose Intensified Radiotherapy for Oligo-progressive Disease in Oncogene-addicted Lung Tumours
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: NSCLC
Keywords: SBRT
Oligoprogressive disease
NSCLC
TKI
Lead sponsor: Institute of Cancer Research, United Kingdom
Sponsor class: OTHER
First posted: 2017-08-22
Enrollment: 113
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression free survival
timeFrame: 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:
measure: Time to next line of systemic therapy or palliative care
timeFrame: 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).
measure: Overall survival
timeFrame: Time from randomisation until death from any cause. Assessed up to 24 months.
measure: Patterns of disease progression identified from CT scans to further document natural history of oncogene-addicted NSCLC
timeFrame: Assessed 3-monthly up to 24 months.
measure: Radiotherapy toxicities (acute events)
timeFrame: Baseline, 8 weeks and 3-monthly intervals during follow-up (a minimum of 6 months).
measure: Radiotherapy toxicities (late events)
timeFrame: Baseline, 8 weeks and 3-monthly intervals during follow-up (a minimum of 6 months).
measure: Quality of Life (EQ-5D-5L)
timeFrame: Baseline, 8 weeks and at the first 3 month visit.
measure: Quality of Life (EORTC QLQ-C30)
timeFrame: Baseline, 8 weeks and at the first 3 month visit.
measure: Measurement of resistant sub-clones in Circulating tumour DNA (ctDNA)
timeFrame: Baseline, 8 weeks post-randomisation and 3-monthly intervals during follow-up (up to 24 months).
measure: Time to failure of next line treatment
timeFrame: Time from randomisation to disease progression on next line of active systemic therapy. Assessed up to 24 months.
Other outcomes:
Locations:
city: Paris
country: France
facility: Institut Gustave Roussy
city: Toulouse
country: France
facility: Institut Claudius Régaud
city: Roma
country: Italy
facility: Policlinico Universitario Campus Bio-Medico
city: Torino
country: Italy
facility: Ospedale San Luigi Gonzaga - Universita Di Torino
city: Barcelona
country: Spain
facility: Hospital Clinic Universitari de Barcelona
city: Barcelona
country: Spain
facility: Institut Català d'Oncologia
city: Seville
country: Spain
facility: University Hospital Virgen del Rocio
city: Bellinzona
country: Switzerland
facility: Oncology Institute of Southern Switzerland
city: Geneva
country: Switzerland
facility: Hopital Cantonal Universitaire De Geneve
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: Zurich
country: Switzerland
facility: UniversitatsSpital Zurich
city: Sutton
country: United Kingdom
facility: Royal Marsden Hosital
state: England
city: Chelsea
country: United Kingdom
facility: Royal Marsden Hospital
state: London
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
state: Surrey
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Hull
country: United Kingdom
facility: Castle Hill Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: London
country: United Kingdom
facility: University College London Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: Manchester
country: United Kingdom
facility: The Christie Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
city: Southampton
country: United Kingdom
facility: Southampton University Hospital
city: Wirral
country: United Kingdom
facility: Clatterbridge Cancer Centre
Study officials:
affiliation: Royal Marsden NHS Foundation Trust
name: Fiona McDonald, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.