Stereotactic Body Radiotherapy for the Treatment of OPD

NCT03256981 | Unknown Phase 2 DMC

• 1 other identifier: ICR-CTSU/2016/10061
• Study Type: interventional
• Target: 113
• Locations: 5 countries
• Sites: 29

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).

Conditions

NSCLC

Keywords

SBRT; Oligoprogressive disease; NSCLC; TKI

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• 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).

• Overall survival

  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

  Assessed 3-monthly up to 24 months.

• Radiotherapy toxicities (acute events)

  Baseline, 8 weeks and 3-monthly intervals during follow-up (a minimum of 6 months).

• Radiotherapy toxicities (late events)

  Baseline, 8 weeks and 3-monthly intervals during follow-up (a minimum of 6 months).

Study Arms (2)

SBRT and continued TKI therapy

EXPERIMENTAL

Patients will continue to receive background TKI treatment as prior to trial entry. Simultaneous administration (SBRT \& TKI) or break in TKI during SBRT will be by centre preference and determined prior to commencing recruitment. Repeat SBRT will be permissible upon development of subsequent OPD lesions dependent on SBRT suitability and total progression lesion number at any one point remaining ≤ 5.

Radiation: SBRT

Continued TKI therapy alone

ACTIVE COMPARATOR

Continuation on the same background TKI treatment as prior to trial entry

Drug: TKI

Interventions

SBRT RADIATION

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

Also known as: Stereotactic body radiotherapy, SABR

SBRT and continued TKI therapy

TKI DRUG

Continued background TKI alone

Also known as: Tyrosine Kinase Inhibitor

Continued TKI therapy alone

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, ≥ 16 years of age
• Established histological diagnosis of advanced NSCLC, not suitable for radical treatment, with defined actionable mutation receiving targeted TKI therapy
• Clinical and/or radiologically confirmed response to TKI therapy (assessed locally usually 2-3 months post commencing TKI)
• 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.
• Adequate baseline organ function to allow SBRT to all relevant targets
• Predicted life expectancy ≥ 6 months
• Karnofsky Index ≥ 60% and ECOG 0-2
• Provision of written informed consent

You may not qualify if:

• \> 5 extracranial sites of progressive disease
• 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.
• 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
• Co-morbidities considered clinically precluding the safe use of SBRT (as detailed in the HALT radiotherapy planning and delivery guidelines).
• Any psychological, sociological or geographical issue potentially hampering compliance with the study
• Pregnancy

Sponsors & Collaborators

• Institute of Cancer Research, United Kingdom: lead

Study Sites (29)

Institut Gustave Roussy

Paris, 94800, France

Location

Institut Claudius Régaud

Toulouse, 31059, France

Location

Policlinico Universitario Campus Bio-Medico

Roma, 00128, Italy

Location

Ospedale San Luigi Gonzaga - Universita Di Torino

Torino, 10043, Italy

Location

Hospital Clinic Universitari de Barcelona

Barcelona, 08036, Spain

Location

Institut Català d'Oncologia

Barcelona, 08908, Spain

Location

University Hospital Virgen del Rocio

Seville, 41013, Spain

Location

Oncology Institute of Southern Switzerland

Bellinzona, 6500, Switzerland

Location

Hopital Cantonal Universitaire De Geneve

Geneva, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

UniversitatsSpital Zurich

Zurich, 8091, Switzerland

Location

Royal Marsden Hosital

Sutton, England, SM2 5PT, United Kingdom

Location

Royal Marsden Hospital

Chelsea, London, SW3 6JJ, United Kingdom

Location

Royal Surrey County Hospital

Guildford, Surrey, GU2 7XX, United Kingdom

Location

Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

Location

Bristol Haematology and Oncology Centre

Bristol, BS2 8ED, United Kingdom

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Castle Hill Hospital

Hull, HU16 5JQ, United Kingdom

Location

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

St Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

Location

University College London Hospital

London, NW1 2PG, United Kingdom

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

The Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

Clatterbridge Cancer Centre

Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

Location

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

Weston Park Hospital

Sheffield, S10 2SJ, United Kingdom

Location

Southampton University Hospital

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34903471 DERIVED

MeSH Terms

Interventions

Radiosurgery; Tyrosine Kinase Inhibitors

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Fiona McDonald, MD

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2017
• First Posted: August 22, 2017
• Study Start: November 27, 2017
• Primary Completion: July 17, 2023
• Study Completion: June 30, 2025
• Last Updated: December 26, 2023

Record last verified: 2023-12

Locations

ES (3); CH (4); FR (2); IT (2); GB (18)