Trial Title:
Stereotactic Ablative Radiotherapy for Oligometastatic Non-small Cell Lung Cancer
NCT ID:
NCT02417662
Condition:
Non-small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Conditions: Keywords:
NSCLC
Stereotactic Ablative Radiotherapy
Radiotherapy
Randomised
Controlled
Oligometastatic
Study type:
Interventional
Study phase:
N/A
Overall status:
Active, not recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
Radical Radiotherapy (Conventional RT and SABR)
Description:
Radical radiotherapy (conventional or SABR) to primary and SABR to the metastases
Arm group label:
SACT + Radical Radiotherapy (Conventional RT and SABR)
Intervention type:
Other
Intervention name:
Non-investigational SACT
Description:
There is no intervention in the control group, patients will receive SACT. The choice of
SACT is determined by the treating clinician and will be supplied from hospital
commercial stock, and prepared and administered according to institutional guidelines.
Arm group label:
Systemic Anti-Cancer Therapy (SACT) alone
Summary:
The trial will assess the addition of stereotactic ablative radiotherapy (SABR) to
standard anti-cancer therapy (SACT) in patients with oligometastatic non-small cell lung
cancer. Patients will be randomised to receive either standard treatment alone (SACT) or
standard treatment with conventional radiotherapy (RT) and SABR.
Detailed description:
SARON is a confirmatory phase III study examining the efficacy and safety of stereotactic
ablative radiotherapy (SABR) and conventional radiotherapy (RT) alongside standard
chemotherapy in patients with oligometastatic non-small cell lung cancer.
Current treatment for this group of patients is systemic anti-cancer therapy. The choice
of SACT is determined by the treating clinician and will be supplied from hospital
commercial stock, and prepared and administered according to institutional guidelines.
There is sufficient evidence regarding the safety of SABR, its effect on local control
and a possible impact on overall survival. This trial will further examine overall
survival, progression free survival and local control, as well as toxicity, feasibility,
patient reported outcomes and health resource use.
There will be a feasibility analysis performed after 50 patients have been randomised.
This will assess the practicality of achieving recruitment targets, logistics of
delivering the experimental treatment and the potential for contamination (as patients
may seek SABR outside of the trial if randomised to the non SABR arm). There will also be
a parallel thoracic SABR safety and feasibility study after recruitment and treatment of
20 patients with thoracic metastases.
This is a multicentre randomised phase III study based on patients with oligometastatic
NSCLC.
Trial arms:
Control Arm: systemic anti-cancer therapy alone (SACT) Experimental Arm: SACT plus
radical RT to primary and SABR and/or SRS to metastases
Criteria for eligibility:
Criteria:
Registration Inclusion criteria
1. Patient ≥ 18 years
2. Histologically or cytologically confirmed NSCLC.
3. Staging with FDG PET-CT whole body scan and MRI brain within 45 days prior to
registration (but prior to commencement of first cycle of SACT). [Note: Brain CT
with IV contrast can be performed instead (within 45 days prior to registration).
However, if brain metastases are evident on the brain CT then a brain MRI must be
performed prior to randomisation, i.e. the Brain CT is sufficient for registration
into the trial but not for randomisation if it is positive for brain metastases, in
which case a brain MRI must be performed]
4. ECOG performance status 0 to 1 (prior to commencement of first cycle of SACT).
5. Patient presenting with primary disease +/- lymph nodes and synchronous
oligometastatic disease (1-5 lesions in up to a maximum of 3 organs).
6. Patient is deemed fit to receive four cycles of systemic anti-cancer therapy,
according to local guidelines and assessment.
7. Patient is deemed fit to receive radical RT (either conventional RT or SABR) to
primary disease +/- lymph node and SABR/SRS to 1-5 metastases according to local
guidelines and assessment.
8. Primary tumour +/- lymph node suitable for radical RT (either conventional RT or
SABR).
9. 1-5 metastatic lesions in up to a maximum of 3 organs, assessable according to
RECIST v1.1 and all of which are suitable for SABR/SRS (only one site of metastasis
or primary tumour needs to be measurable according to RECIST v1.1).
i. If brain metastasis present, the NHS commissioning guidelines need to be met for
intracranial SRS (≤20 cc) (or equivalent for Wales, Scotland & Northern Ireland in
line with standard of care).
ii. Lymph nodes included in the N1-3 categories of the IASLC 2009 staging criteria
are treated in the conventional radiotherapy volume and are not counted as
metastases.
iii. Lymph nodes not included in the N1-3 categories of the IASLC 2009 staging
criteria, e.g. pelvic lymph nodes, are counted as metastases.
iv. For bone metastases pre-SABR stabilisation should be considered as clinically
appropriate. This does not exclude the patient from the study.
10. Acceptable lung function for radical lung radiotherapy as assessed according to
local policy. Note: Potential thoracic sub-study patients will need to complete
pulmonary function tests pre-randomisation
11. No relevant co-morbidities, including UIP pulmonary fibrosis and connective tissue
disorders.
Additional inclusion Information Patients with lung cancer and an additional malignant
nodule are difficult to categorise, and the current stage classification rules are
unclear. Such patients should be evaluated by the local multidisciplinary team to
determine whether the additional lesion represents a second primary lung cancer or an
additional tumour nodule corresponding to the dominant cancer. The SARON TMG will accept
local MDM decisions on this and will centrally review all baseline imaging
retrospectively
Registration Exclusion Criteria
1. Patient has had palliative radiotherapy to any tumour site prior to registration or
requires palliative radiotherapy prior to randomisation.
2. Presence of an actionable molecular aberration.
3. Patients currently receiving VEGF inhibitors.
4. One or more metastases previously treated with alternative ablative treatment.Note:
Surgical ablation (partial or total excision biopsy) is permitted for palliative or
diagnostic purposes (e.g. for molecular analysis). Treatment for any residual
disease/tumour bed will be at the discretion of treating clinician/MDT.
Resected/ablated metastases will count towards the total number of metastases.
5. Patient has received any previous treatment for this NSCLC malignancy.
6. Patients who present with brain metastasis only and no sites of extra cranial
metastatic disease i.e. the presence of more than 4 brain metastases is an exclusion
criterion.
7. Metastasis in sites where normal radiotherapy OAR constraints cannot be met.
8. Brain metastasis within the brainstem.
9. Patients who have more than five sites of metastases in up to 3 organs prior to
trial registration.
10. Primary tumour or metastases causing direct invasion or high clinical suspicion of
direct invasion of the wall of a major blood vessel, oesophagus, trachea, proximal
bronchial tree, stomach, intestines or mesenteric lymph nodes or cutaneous
metastases or diffuse serosal metastases.
11. Malignant pleural or pericardial effusion.
12. Bilateral adrenal metastases.
13. History of prior malignant tumour likely to interfere with the protocol treatment,
(patients without evidence of disease for at least 1 year or a non-melanoma skin
tumour or early cervical cancer are eligible).
14. Women who are pregnant or breast feeding.
15. Stage III disease with extensive nodal disease not treatable in radical radiotherapy
field.
16. Leptomeningeal disease
Eligibility Criteria for Randomisation
Following cycle 2 of induction SACT, patients must meet the following eligibility
criteria for randomisation:
- No confirmed disease progression on post-cycle 2 CT scan (according to RECIST v1.1)
- Patients with up to 5 metastases at the time of registration but less than 5
visible after induction SACT are still eligible for randomisation.
- Patients with no visible metastases following 2 cycles of induction of SACT are
eligible for randomisation. If randomised to the Investigational Arm, these
patients will receive RT upon relapse of metastases (patients who experience
progression with new metastases are not eligible for randomisation or for trial
treatment).
- Patients with complete response of the lung primary +/- lymph nodes following 2
cycles of induction SACT are eligible for randomisation. Patients randomised to
the Investigational Arm, should receive conventional RT to the pre-SACT
involved nodal stations and to any scar residuum at the primary site.
- Patients who progress following 2 cycles of induction of SACT cannot be
randomised. Only overall survival data will be collected for these patients.
- ECOG Performance Status 0-2.
- Continued suitability for trial treatment as deemed by the treating clinician.
- Continues to meet all registration eligibility criteria, as detailed in section
6.4.1 (with the exception of ECOG status).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
UCLH
Address:
City:
London
Country:
United Kingdom
Facility:
Name:
Belfast City Hospital
Address:
City:
Belfast
Country:
United Kingdom
Facility:
Name:
Queen Elizabeth Hospital
Address:
City:
Birmingham
Country:
United Kingdom
Facility:
Name:
Bristol Royal Infirmary
Address:
City:
Bristol
Country:
United Kingdom
Facility:
Name:
Addenbrooke's Hospital
Address:
City:
Cambridge
Country:
United Kingdom
Facility:
Name:
BEATSON
Address:
City:
Glasgow
Country:
United Kingdom
Facility:
Name:
Royal Surrey County Hospital
Address:
City:
Guildford
Country:
United Kingdom
Facility:
Name:
St James's University Hospital
Address:
City:
Leeds
Country:
United Kingdom
Facility:
Name:
Leicester Royal Infirmary
Address:
City:
Leicester
Country:
United Kingdom
Facility:
Name:
Guy's and St Thomas's Hospital
Address:
City:
London
Country:
United Kingdom
Facility:
Name:
St Bart's Hospital
Address:
City:
London
Country:
United Kingdom
Facility:
Name:
The Royal Marsden Hospital
Address:
City:
London
Country:
United Kingdom
Facility:
Name:
Christie Hospital
Address:
City:
Manchester
Country:
United Kingdom
Facility:
Name:
The James Cook University Hospital
Address:
City:
Middlesbrough
Country:
United Kingdom
Facility:
Name:
Freeman Hospital
Address:
City:
Newcastle
Country:
United Kingdom
Facility:
Name:
City Hospital
Address:
City:
Nottingham
Country:
United Kingdom
Facility:
Name:
Weston Park Hospital
Address:
City:
Sheffield
Country:
United Kingdom
Facility:
Name:
Southampton General Hospital
Address:
City:
Southampton
Country:
United Kingdom
Facility:
Name:
Clatterbridge Cancer Centre
Address:
City:
Wirral
Country:
United Kingdom
Start date:
August 19, 2016
Completion date:
August 2028
Lead sponsor:
Agency:
University College, London
Agency class:
Other
Collaborator:
Agency:
Cancer Research UK
Agency class:
Other
Source:
University College, London
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT02417662
