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Trial registered on ANZCTR


Registration number
ACTRN12613000239763
Ethics application status
Not yet submitted
Date submitted
23/02/2013
Date registered
28/02/2013
Date last updated
28/02/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase II Feasibility Study of Lipidiol Markers for Radiation Therapy Localisation and Response Assessment in the Multi-Disciplinary Team Management of Oesophageal-Gastric Cancer
Scientific title
Phase II Feasibility Study of Lipidiol Markers for Radiation Therapy Localisation and Response Assessment in the Multi-Disciplinary Team Management of Oesophageal-Gastric Cancer
Secondary ID [1] 282017 0
Nil
Universal Trial Number (UTN)
U1111-1139-8195
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Oesophageal-gastric cancer 288462 0
Condition category
Condition code
Cancer 288807 288807 0 0
Stomach
Cancer 288808 288808 0 0
Oesophageal (gullet)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Lipiodol is a stable fatty acid ethyl ester which is a derivative of poppy seed oil which has a wide range of applications in current medical practice which include localisation of hepatocellular carcinoma. Endoscopically inserted lipiodol is currently utilized for the treatment of bleeding gastric varices in combination with Histoacryl (n-butyl cyanoacrylate) which acts as a glue in order to prevent extravasation of the lipiodol. Currently surrogate markers exist in the form of standard surgical heamaclips have been routinely used in neurosurgery, thoracic surgery, breast surgery and abdominal surgery for 50+ years. Radiotherapy fields can be more accurately marked and treatment delivered using surgical clips.
At present only one study utilizing lipiodol injection as a surrogate marker for localization prior to radiotherapy planning exists. This study utilized trans-rectal ultrasound guidance to inject lipiodol into the prostate. However there has been extensive experience in the use of lipiodol and histoacryl in the treatment of gastric varices where it has been shown to be a safe and effective therapy with minimal complications.

Whilst the combination of lipiodol/histoacryl are not yet standard therapy for localization of tumours, however given the promise of the initial pilot study the Urology unit at Austin health are also further investigating the utility of lipiodol marking of prostate cancers. Further more at Austin Health it is standard practice for patients who require radiotherapy for prostate cancer to have gold seed fiducials as surrogate markers inserted into their prostate glands before treatment. This helps to track the location of the prostate during radiotherapy. It is standard practice for patients who require radiotherapy for breast cancer to have titanium heamaclip fiducials inserted in the breast at surgery before radiotherapy.

The use of lipiodol markers for the purpose of assessing tumour response in oesophageal cancer is something that has not been published previously. One previous pilot study has demonstrated the feasibility and safety of using metal fiducials in oesophageal cancer, gastric and pancreatic cancers for surgical pathologic correlation and/or image guided radiotherapy. This has been supported by our own recent experience with gold fiducial insertion in gastro-oesophageal cancers.

Endoscopic tattooing is standard of care in gastrointestinal tract tumours (oesophageal, gastric, colonic). At present carbon particles (SPOT), Indocyanine green and India ink are currently used to mark these lesions. However they are radiolucent whereas lipiodol which is radio-opaque and therefore should act as a marker for radiotherapy as seen in the previous study performed in the prostate.

A submucosal injection into normal muocsa adjacent to the tumour will be performed through the gastroscope with 1.4mls of saline, followed by 0.4mls of lipiodol:0.4mls of histoacryl solution to prevent extravasation of the lipiodol. This procedure will be performed 4 x to outline the superior/inferior and lateral margins of the tumour. This will be performed as a once off procedure. The duration of the markers will be dictated by the patient's treatment pathway (eg. if curative then will be resected in surgical specimen at time of the operation).
Whether a patient proceeds to radiotherapy, its duration, intensity etc will be discussed for each participant at the multi disclipinary meeting prior to marker insertion. The markers have no impact on the type or duration of the radiotherapy involved and each patient will receive current standard of care treatment.
Intervention code [1] 286595 0
Treatment: Other
Comparator / control treatment
Phase 2 feasibility study therefore no comparator/control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 288945 0
The rate of successful lipiodol placement without complications for response assessment and anatomical localisation
Timepoint [1] 288945 0
Endoscopic assessment of successful insertion at the time of lipiodol based marking and or follow up radiological evidence of the markers.
Secondary outcome [1] 301406 0
Visibility of markers for radiotherapy planning
Timepoint [1] 301406 0
As identified at the timing of radiotherapy planning for image guided radiotherapy
Secondary outcome [2] 301407 0
Cost analysis of lipiodol markers in comparison to alternative methods such as fiducial/endoclip placement.
Timepoint [2] 301407 0
Following endoscopic marker insertion a cost analysis of the lipiodol marking against the previous gold fiducial insertion under EUS guidance will be performed.
Secondary outcome [3] 301408 0
The rate of successful anatomical correlation of both pre and post neoadjuvant therapy lipiodol images.
Timepoint [3] 301408 0
At the time of followup imaging after completion of neoadjuvant therapy.
Secondary outcome [4] 301409 0
The rate of successful (RECIST) assessment of tumour response post neoadjuvant therapy.
Timepoint [4] 301409 0
Performed following curative therapy as discussed fortnightly during the Upper GI MDT.
Secondary outcome [5] 301410 0
The quantitative improvement in RECIST reporting with lipiodol.
Timepoint [5] 301410 0
Performed following curative/palliative therapy as discussed at the upper GI MDT
Secondary outcome [6] 301411 0
The quantitative improvement in correlating metabolic response with pathologic response rate with lipiodol.
Timepoint [6] 301411 0
Followup imaging after curative/palliative therapy.
Secondary outcome [7] 301412 0
The rate of successful spatial correlation of pathologic margin (macro and micro) correlation with conventional imaging. (CT, EUS and FDG-PET/CT)
Timepoint [7] 301412 0
At the completion of above mentioned investigations following insertion of markers.
Secondary outcome [8] 301413 0
Spatial correlation of CT, EUS and FDG-PET/CT and oesophagectomy specimens with radiotherapy volumes in definitive and postoperative settings.
Timepoint [8] 301413 0
Following surgical resection of oesophageal cancer.

Eligibility
Key inclusion criteria
Biopsy-proven primary (non-recurrent) squamous cell carcinoma or adenocarcinoma of the oesophagus or stomach
Expected survival of at least 3 months
Age greater than 18 years
Medically suitable for radiotherapy
Written informed consent
Minimum age
18 Years
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Contraindications to CT contrast e.g. severe chronic kidney disease, allergy to contrast
Contraindications to PET/CT e.g. claustrophobia

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All patients are discussed at the upper GI MDT at Austin health on a fortnightly basis. Those patients with either oesophageal/gastric cancers who are for curative/palliative treatment pathways are discussed and if fulfill inclusion criteria will be identified as suitable for enrollment. The patient will then be invited to participate during their outpatient consultation where if they proceed will then require to sign a patient information and consent form.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Small phase 2 study that will use primarily descriptive statistics.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/04/2013
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 667 0
Austin Health - Heidelberg Repatriation Hospital - Heidelberg West
Recruitment postcode(s) [1] 6404 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 286791 0
Self funded/Unfunded
Name [1] 286791 0
Austin Health department of gastroenterology and department of radiation oncology
Country [1] 286791 0
Australia
Primary sponsor type
Hospital
Name
Austin Health
Address
Austin Health.
145 Studley Road, Heidelberg Victoria, Australia.
Country
Australia
Secondary sponsor category [1] 285582 0
None
Name [1] 285582 0
Address [1] 285582 0
Country [1] 285582 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 288859 0
Austin HREC
Ethics committee address [1] 288859 0
Level 6 Harold Stokes Building
145 Studley Road.
Austin Health
Ethics committee country [1] 288859 0
Australia
Date submitted for ethics approval [1] 288859 0
26/02/2013
Approval date [1] 288859 0
Ethics approval number [1] 288859 0

Summary
Brief summary
Patients involved:
Those patients with oesophageal-gastric cancer.

Intervention:
Insertion of lipiodol markers under endoscopic guidance that will allow improved response assessment with imaging such as CT, surgical resection and pathological assessment of the tumour in the surgical specimen. Intervention will also allow image guided radiotherapy for candidates who are suitable for radiotherapy.

Outcomes of this study:
The outcomes include success of lipiodol marker insertion which will be classified endoscopically and or radiologically on follow up imaging.
Visibility of markers for radiotherapy planning
Cost analysis of lipiodol markers in comparison to alternative methods such as fiducial/endoclip placement.
The rate of successful anatomical correlation of both pre and post neoadjuvant therapy lipiodol images.
The rate of successful (RECIST) assessment of tumour response post neoadjuvant therapy.
The quantitative improvement in RECIST reporting with lipiodol.
The quantitative improvement in correlating metabolic response with pathologic response rate with lipiodol.
The rate of successful spatial correlation of pathologic margin (macro and micro) correlation with conventional imaging. (CT, EUS and FDG-PET/CT)
Spatial correlation of CT, EUS and FDG-PET/CT and oesophagectomy specimens with radiotherapy volumes in definitive and postoperative settings
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 38102 0
Dr Sujievvan Chandran
Address 38102 0
145 Studley Road, Level 8 Harold Stokes Building, Department of Gastroenterology, Austin Health, Heidelberg, Victoria 3084, Australia.
Country 38102 0
Australia
Phone 38102 0
+61,03,94965000
Fax 38102 0
Email 38102 0
[email protected]
Contact person for public queries
Name 38103 0
Dr Sujievvan Chandran
Address 38103 0
145 Studley Road, Level 8 Harold Stokes Building, Department of Gastroenterology, Austin Health, Heidelberg, Victoria 3084, Australia.
Country 38103 0
Australia
Phone 38103 0
+61,03,94965000
Fax 38103 0
Email 38103 0
[email protected]
Contact person for scientific queries
Name 38104 0
Dr Sujievvan Chandran
Address 38104 0
145 Studley Road, Level 8 Harold Stokes Building, Department of Gastroenterology, Austin Health, Heidelberg, Victoria 3084, Australia.
Country 38104 0
Australia
Phone 38104 0
+61,03,94965000
Fax 38104 0
Email 38104 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseA novel endoscopic marker for radiological localization and image-guided radiotherapy in esophageal and gastric cancers (with video).2016https://dx.doi.org/10.1016/j.gie.2015.06.042
N.B. These documents automatically identified may not have been verified by the study sponsor.