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Trial registered on ANZCTR


Registration number
ACTRN12618001789257
Ethics application status
Approved
Date submitted
15/10/2018
Date registered
1/11/2018
Date last updated
1/11/2018
Date data sharing statement initially provided
1/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of changing the order of scans in making a diagnosis of lung cancer.
Scientific title
PET/CT FIRST: A Prospective study of up-front PET/CT in guiding minimisation of number of diagnostic interventions of pulmonary nodules suspicious for lung cancer.
Secondary ID [1] 296335 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lung cancer 310053 0
Condition category
Condition code
Cancer 308809 308809 0 0
Lung - Non small cell
Cancer 308810 308810 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1. A PET/CT to determine which diagnostic procedure should be done first- all subjects in the study have this. This is done once at study entry. Initially the referral CT scan will be reviewed by the study group for every patient and a provisional diagnostic test will be recommended( EBUS Guide sheath versus CT FNA versus Surgical excision biopsy versus observation and repeat scan). Then ALL patients have a PET/CT - on the study hospital campus- (RBWH / Sir Charles Gairdner Hospital. ) . The study group will then RECONVENE after the PET/CT is done and review that original biopsy choice decision based on alternate targets revealed by the PET/ CT. It is only then that the diagnostic test will actually be done- on the basis of those reviews. The diagnostic tests will be done in the usual way by the thoracic team- patients are not randomised to a specific intervention, only allocated on the basis of the PET CT and how it changes the initial diagnostic test. If a PET/CT has been done elsewhere, that study can be used in the evaluations as above without repeating it.
2. A CT low dose) to enable detailed assessment of a nodule particularly with a view to virtual bronchoscopy planning. This is done in all cases, once at study entry, at the same time as the PET/CT and is similarly reviewed by the study group and the radiologist to determine the presence or absence of a bronchus sign and how this differs from the referral CT and how this may influence the decision for a bronchoscopic approach. That is, it is reviewed once, by the radiologists as part of the study team, before any biopsy is done. We would check that such a scan had not been done before referral.
3. Blood test sampling for exosome analysis. This is done once at study entry at the time of insertion of cannula for the PET CT procedure. This does not influence management and does not lead to any intervention in itself.

Intervention code [1] 312663 0
Diagnosis / Prognosis
Comparator / control treatment
Comparator is the test which was regarded as being the best first diagnostic test WITHOUT PET/CT. that is, the diagnostic test recommended on ONLY the referral CT is documented by the study group prior to the PET/CT. Patients are their own control.
For the benefit of the VB CT this will be expressed as the difference in proportion of diagnostic yield of malignancy for each group (cases from this study versus historic controls from our Unit from the last 2 years), compared with a T test.
Control group
Active

Outcomes
Primary outcome [1] 307789 0
The study group will record decision making of first diagnostic test ( both before and after PET/CT) in the study data base. these are commonly made decisions, and rest on the position of the nodule ( more peripheral means more likely to have a CT FNA), whether associated with a bronchus - more likely to have a bronchoscopy with ebus guide sheath), classic features of a cancer in a fit patient with excellent lung function and a high risk prediction score for cancer ( might be considered direct for surgery),
so the outcome is CHANGE of biopsy strategy.
Timepoint [1] 307789 0
Pre and Post the PET CT
Primary outcome [2] 307829 0
Outcomes of biopsy sampling by pathology results - SENSITIVITY FOR MALIGNANCY BY TEST TYPE.
Timepoint [2] 307829 0
At entry, on basis of the final biopsy proven diagnosis
Primary outcome [3] 307860 0
Clinical parameters regarding biopsy type- adverse events/ mortality
Timepoint [3] 307860 0
At the time of initial biopsy or procedure - up to first month post study inclusion.
Secondary outcome [1] 352892 0
presence of air bronchograms on low dose CT chest: by radiologist report, comparing the initial referral CT chest, and this study CT. : the study group will record decision making of first diagnostic test ( both before and after low dose CT) in the study data base .
Timepoint [1] 352892 0
Pre and Post low dose CT chest
Secondary outcome [2] 352893 0
Diagnostic accuracy (sensitivity and specificity) of blood exosome test to identify cancerous modules as assessed by comparison to final pathologic diagnosis.
Timepoint [2] 352893 0
the result of the exosome test will be compared to final pathologic diagnosis once all lab pathology tests for tissue confirmation are available at the initial diagnostic workup (this may take up to 2-3 weeks for a final diagnosis to be made).

Eligibility
Key inclusion criteria
• Referrals to Thoracic Medicine OPD or Inpatient Consults
• Nodules 8-30mm diameter, solid or semi-solid
• Brock risk calculator risk of malignancy of >10%
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Unsuitable for bronchoscopy
• where nodules have morphology clearly suggestive of benign disease per BTS guidelines
peri-fissural or subpleural nodules less than 10 mm diameter.
o Ground Glass opacity nodules with less than 5 mm solid component – see reference
• Pregnant or lactating women

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis
Overall we therefore expect that PET CT will give a combined change in the diagnostic procedure ( to either an EBUS TBNA or sampling of a distant metastasis) in 20%. From a baseline of 78% having either an EBUS GS or a CT TTNA, this will reduce to 58%, with the remainder having other biopsies as stated. It is assumed that because of the very high yield of these other biopsies this would represent a 20% increase in the number of patients having a single diagnostic test. Using a change from 78% to 58% and an alpha of 0.05 and a beta of 0.8 for 2 groups with a single dichotomous variable (lung nodule biopsy or not) the total sample size is 168 patients, 84 in each group.

Outcomes
As per the Primary and secondary outcomes results would be expressed as proportions of each analysis pre and post the PET/CT, and compared using a paired T test.
For the benefit of the VB CT this will be expressed as the difference in proportion of diagnostic yield of malignancy for each group (cases from this study versus historic controls from our Unit), compared with a T test.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,WA
Recruitment hospital [1] 12182 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [2] 12183 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 24351 0
4029 - Herston
Recruitment postcode(s) [2] 24352 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 300940 0
Hospital
Name [1] 300940 0
Royal Brisbane and Womens Hospital
Address [1] 300940 0
Bowen Bridge Road &, Butterfield St. Herston Qld 4029
Country [1] 300940 0
Australia
Primary sponsor type
Hospital
Name
Royal Brisbane and Womens Hospital
Address
Bowen Bridge Road &, Butterfield St. Herston Qld 4029
Country
Australia
Secondary sponsor category [1] 300512 0
None
Name [1] 300512 0
Address [1] 300512 0
Country [1] 300512 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301706 0
Royal Brisbane and Womens Hospital Human Research Ethics Committee
Ethics committee address [1] 301706 0
Bowen Bridge Road & Butterfield St.
Herston
Qld 4029
Ethics committee country [1] 301706 0
Australia
Date submitted for ethics approval [1] 301706 0
26/02/2018
Approval date [1] 301706 0
16/04/2018
Ethics approval number [1] 301706 0
HREC/18/QRBW/107

Summary
Brief summary
Brief description of the study purpose
You may be eligible for this study if you attend either the Royal Brisbane & Womens Hospital in Queensland or the Sir Charles Gairdner Hospital in Western Australia and have a nodule on the lung suspicious for cancer.

Who is it for?
Your doctor has sent you to have tests to investigate a spot (nodule) on your lung. Taking samples of the nodule may require by a bronchoscopy ( a camera into the lung) or samples taken with a thin needle passed directly into the nodule through the chest wall (directed by a CAT scanner).

Study details
PET/CT scans are approved in Australia when patients have lung nodules PET/CT scans are a way to take pictures of the lung and the rest of the body to show up “hot spots”and whether there are any other hot spots in the body that need to sampled.
This study is seeing how putting PET/CT first (ie before any other tests) might improve the way all nodules are tested. If other spots in the lung or in lymph nodes or in other parts of the body are shown on PET/CT scan before any biopsies are done, it may be that doctors decide to biopsy those other spots first, rather than the nodule, to give the best information to allow treatment of your condition with one test, not two or three.
All study participants will have a PET/CT first. They will also have detailed CT scan of the chest up front as well to possibly improve detection of the nodule. They will aslo all have a blood test, to study the use of new technology to confirm whether a nodule may be cancerous by just doing a blood test. There is no randomisation and all patients will have these tests before their other investigations.

The purpose of this study is to determine whether using a test first (a PET/CT scan) when diagnosing cancer, changes the way a cancer is tested- which sampling test should come first. We hope it improves health outcomes by reducing the total number of tests a patient needs.
Trial website
Trial related presentations / publications
Public notes
Attachments [2] 3170 3170 0 0
Attachments [3] 3171 3171 0 0
Attachments [4] 3172 3172 0 0

Contacts
Principal investigator
Name 87830 0
A/Prof David Fielding
Address 87830 0
Dept Thoracic Medicine
Royal Brisbane and Womens Hospital
Bowen Bridge Rd and Butterfield Street
Herston
Qld 4029
Country 87830 0
Australia
Phone 87830 0
+61 7 36464241
Fax 87830 0
+61 7 36465651
Email 87830 0
david.fielding@health.qld.gov.au
Contact person for public queries
Name 87831 0
A/Prof David Fielding
Address 87831 0
Dept Thoracic Medicine
Royal Brisbane and Womens Hospital
Bowen Bridge Rd and Butterfield Street
Herston
Qld 4029
Country 87831 0
Australia
Phone 87831 0
+61 7 36464241
Fax 87831 0
+61 7 36465651
Email 87831 0
david.fielding@health.qld.gov.au
Contact person for scientific queries
Name 87832 0
A/Prof David Fielding
Address 87832 0
Dept Thoracic Medicine
Royal Brisbane and Womens Hospital
Bowen Bridge Rd and Butterfield Street
Herston
Qld 4029
Country 87832 0
Australia
Phone 87832 0
+61 7 36464241
Fax 87832 0
+61 7 36465651
Email 87832 0
david.fielding@health.qld.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
No policy on this issue forthcoming from our HREC.
We would still notify all patients of the overall study outcomes.
What supporting documents are/will be available?
No other documents available
Summary results
Not applicable