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).
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
113
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 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)
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)
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.
Time frame: Baseline, 8 weeks and 3-monthly intervals during follow-up (a minimum of 6 months).
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Institut Gustave Roussy
Paris, France
Institut Claudius Régaud
Toulouse, France
Policlinico Universitario Campus Bio-Medico
Roma, Italy
Ospedale San Luigi Gonzaga - Universita Di Torino
Torino, Italy
Hospital Clinic Universitari de Barcelona
Barcelona, Spain
Institut Català d'Oncologia
Barcelona, Spain
University Hospital Virgen del Rocio
Seville, Spain
Oncology Institute of Southern Switzerland
Bellinzona, Switzerland
Hopital Cantonal Universitaire De Geneve
Geneva, Switzerland
Kantonsspital St. Gallen
Sankt Gallen, Switzerland
...and 19 more locations
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.
Time frame: 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
Time frame: Baseline, 8 weeks and at the first 3 month visit.
Quality of Life (EORTC QLQ-C30)
Assessed using 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.