Conventional Care Versus Radioablation (Stereotactic Body Radiotherapy) for Extracranial Oligometastases
- Conditions
- Carcinoma, Non-Small-Cell LungProstate CancerBreast Cancer
- Interventions
- Other: Standard of CareRadiation: SBRT
- Registration Number
- NCT02759783
- Lead Sponsor
- Royal Marsden NHS Foundation Trust
- Brief Summary
Metastatic spread of cancer from its primary site to distant organs is the commonest cause of death from cancer. The term oligometastases describes an intermediate metastatic state, in which cancer exists as a limited number of metastases at first, before cells acquire the ability to metastasise more widely. For the large majority of solid cancers, once metastatic disease has been diagnosed the chances of cure are small. There are several situations where this is not the case, but it is not known if stereotactic body radiotherapy (SBRT) for oligometastatic disease will alter outcomes or whether the toxicity burden of this treatment is justified. SBRT is targeted radiotherapy which destroys cancer cells in the area of the body it is aimed at however low dose radiation may be received by surrounding tissue.
It is difficult to quantify incidence of patients with multiple primary cancers developing at intervals that are representative of oligometastatic stage IV disease, (defined for the purposes of this trial as ≤ 3 metastatic sites). However an increase in the use of surveillance imaging, together with improved diagnostic sensitivity has led to the diagnosis of patients with asymptomatic oligometastatic relapse becoming a more common clinical occurrence. The CORE study is a randomized controlled trial that will be conducted in patients with cancer in one of three primary sites where oligometastatic disease relapse is a common clinical scenario: breast, prostate and non-small cell lung cancer (NSCLC). The study will evaluate the use of SBRT in this patient population.
Eligible patients who consent to participate in this clinical trial will be randomized to receive standard care or standard care plus SBRT we hope to recruit approximately 206 patients to the study and the primary outcome measure is progression free survival.
- Detailed Description
CORE is a phase II/III, multi-centre, non-blinded, parallel group randomised controlled trial in patients with breast, prostate or NSCLC primary cancer comparing standard of care (SOC) with or without SBRT for extra-cranial metastases. The aim of the phase II study is to demonstrate 1) feasibility of recruitment, 2) deliverability of the study in a multi-centre setting and 3) activity of SBRT, based on progression free survival, across the three tumour types. If all three aims are achieved the trial will be amended to roll into parallel tumour-site specific phase III trials.
Eligible patients are those with either primary breast, prostate or NSCLC who have presented with ≤3 extra-cranial, metachronous, oligometastases, all suitable for SBRT. Patients will be randomised in a 1:1 ratio to either SOC or SOC with the addition of SBRT. Choice of SOC treatment is at the discretion of the local oncologist and defined per patient prior to randomisation (see section 8). Patients randomised to SBRT+SOC will receive a dose and fractionation regimen dependent on the metastatic site and proximity to dose limiting organs and normal tissues. Treatment will take place within 6 weeks of randomisation. The average scheme would be 3 treatments over 5 days but the maximum period of SBRT duration could be 8 treatments over 19 days.
All patients will be reviewed every 3 months with a clinical examination and tumour markers (where applicable) during years 1 and 2, and 6 monthly thereafter to 5 years. Staging and follow up imaging protocols will be tumour type dependent:
* Breast: 3 monthly CT scans for years 1 and 2, and 6 monthly thereafter to 5 years.
* NSCLC: 3 monthly CT scans for years 1 and 2, 6 monthly to year 3, then annually to 5 years.
* Prostate: CT scans will be performed at 6, 12 and 24 months with imaging triggered by appropriate PSA rises. A rising PSA defined as 2 successive PSA rises from nadir, measured a minimum of 4 weeks apart. If the overall PSA rise has a doubling time of ≥ 3 months or the PSA level has doubled the original PSA value at trial entry or if clinically indicated, then restaging should be considered.
All patients will have a toxicity assessment at each clinic visit and patient reported quality of life (QOL) assessment at 3, 6, 12, 18 and 24 months.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 245
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard of Care Standard of Care Standard of care (SOC) is at the discretion of the local oncologist. Standard of Care + SBRT Standard of Care Patients randomised to SBRT will receive a dose and fractionation regimen dependent on the metastatic site and proximity to normal tissues. If allocated to SBRT, SBRT will precede SOC. Standard of Care + SBRT SBRT Patients randomised to SBRT will receive a dose and fractionation regimen dependent on the metastatic site and proximity to normal tissues. If allocated to SBRT, SBRT will precede SOC.
- Primary Outcome Measures
Name Time Method Progression Free Survival 60 months post treatment Time from randomisation to evidence of progression of cancer at any site or death from any cause
- Secondary Outcome Measures
Name Time Method Overall Survival 60 months post treatment Time from randomisation until time of death from any cause
Clinical reported acute and late toxicity 60 months post treatment Clinician reported acute and late toxicity will be graded using NCI CTCAE v4.0 / RTOG systems. Acute events are defined as those occurring up to 3 months follow-up; late events are reported from 6 months post randomisation.
Feasibility of recruitment 3 years from first patient Recruitment rate and proportion of patients receiving SBRT (if allocated) in the absence of new developing widespread disease
Patient reported Quality of Life Pre-treatment and at 3,6,12,18 and 24 months post treatment Patient reported quality of life will be measured using EORTC QLQ C30
Feasibility of SBRT delivery 3 years from first patient Recruitment of patients receiving SBRT within the dosimetric constraints
Local lesion control 60 months post treatment Time from randomisation until radiological evidence of progression at the treated site and be measured on a lesion based on analysis using RECIST criteria.
Trial Locations
- Locations (29)
The Christie Hospital
🇬🇧Manchester, United Kingdom
Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Calvary Mater Newcastle
🇦🇺Waratah, New South Wales, Australia
Princess Alexandra Hospital
🇦🇺Brisbane, Queensland, Australia
James Cook University Hospital
🇬🇧Middlesborough, United Kingdom
Freeman Hospital
🇬🇧Newcastle upon Tyne, United Kingdom
St Bartholomew's Hospital
🇬🇧London, United Kingdom
Belfast City Hospital
🇬🇧Belfast, United Kingdom
Royal Brisbane and Women's Hospital
🇦🇺Brisbane, Queensland, Australia
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Western Australia, Australia
Churchill Hospital
🇬🇧Oxford, Oxfordshire, United Kingdom
Mount Vernon Cancer Centre
🇬🇧London, Surrey, United Kingdom
The Beatson
🇬🇧Glasgow, United Kingdom
St James's University Hospital
🇬🇧Leeds, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
Royal Marsden Hospital
🇬🇧Sutton, United Kingdom
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
GenesisCare - Adelaide Radiotherapy Centre
🇦🇺Adelaide, South Australia, Australia
Bristol Haematology and Oncology Centre
🇬🇧Bristol, United Kingdom
Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
Royal Surrey County Hospital
🇬🇧Guildford, United Kingdom
Nottingham City Hospital
🇬🇧Nottingham, United Kingdom
University College Hospital
🇬🇧London, United Kingdom
Weston Park Hospital
🇬🇧Sheffield, United Kingdom
Clatterbridge Cancer Centre
🇬🇧Wirral, United Kingdom
Austin Health
🇦🇺Melbourne, Victoria, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Guy's Hospital
🇬🇧London, United Kingdom