The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12617001242314
Ethics application status
Approved
Date submitted
25/07/2017
Date registered
25/08/2017
Date last updated
6/11/2018
Date data sharing statement initially provided
6/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Endoscopic Ultrasound Guided portal vein sampling as an ultimate staging procedure in patients with pancreatic cancer: a feasibility study.
Scientific title
Endoscopic Ultrasound Guided portal vein sampling as an ultimate staging procedure in patients with pancreatic cancer: a feasibility study.
Secondary ID [1] 292459 0
None.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pancreatic Cancer 304073 0
Condition category
Condition code
Cancer 303409 303409 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
EUS guided portal vein sampling as an ultimate staging procedure in patients with pancreatic cancer: a feasibility study.
The initial stages of the study will only involve patients with metastatic pancreatic cancer and thus very limited life expectancy. Once deemed safe, the study can then include patients with locally advanced or resectable disease. All aspects of this study will be discussed with each patient during the recruitment process. An information sheet will be provided, and each patient will be given the opportunity to discuss this study will a medical practitioner, friends or family prior to involvement. Each participant will give written, informed consent and will be free to withdrawal from the study at any time.
Management of anti-coagulants and anti-platelets will be organised prior to the procedure as per the standard RAH Gastroenterology policies. A 5 ml sample of peripheral blood will be taken on the day of (prior to) the procedure. Patients will also be given prophylactic intravenous antibiotics 30 minutes prior to the procedure:
1. 1 gm Amoxycillin, 500mg Metronidazole and 6mg/kg dose of Gentamicin
2. For those with GFR <60 mL/minute: 1gm Ceftriaxone and 500mg Metronidazole

The endoscopist will administer the intervention.
Following standard EUS FNA of the mass lesion with a linear-array echoendoscope, the intra-hepatic branches of the portal vein will be located. To decrease the risk of bleeding, the site of portal vein puncture will be in an area where the needle will travel at least 15mm through liver parenchyma (i.e. there will be at least 15mm of hepatic tissue between the scope and the portal vein puncture site). Puncture of the portal vein will be done using a 22-gauge EUS FNA needle. The stylet within the needle will then be withdrawn and aspiration of blood will confirm the position of the needle. A 5 ml sample of portal venous blood will be aspirated.
The samples are stored at room temperature (15-30 degrees Celsius) for testing that will be done within 96 hours. For KRAS mutation analyses, 5 ml of peripheral blood and 5ml of portal venous blood will be collected in tubes designed to stablise the RNA (KRAS seven mutations detection kit). The tubes will be processed (extraction and purification) according to the manufacturers’ instructions .
Patients will be monitored for 90 minutes in our recovery unit for complications and pain scores. Blood tests will be done within 24 hours to monitor for any significant decline in haemoglobin.
Intervention code [1] 298639 0
Diagnosis / Prognosis
Comparator / control treatment
Comparing outcomes between the three groups of patients (metastatic, locally advanced and resectable)
Control group
Active

Outcomes
Primary outcome [1] 302799 0
To investigate the differences in the % of KRAS mutations found in circulating cell free tumour DNA between the groups of patients treated for:
1. metastatic pancreatic cancer;
2. Locally advanced pancreatic cancer;
3. Resectable pancreatic cancer.

For KRAS mutation analyses, 5 ml of peripheral blood and 5ml of portal venous blood will be collected in tubes designed to stablise the RNA (KRAS seven mutations detection kit). The tubes will be processed (extraction and purification) according to the manufacturers’ instructions.
Timepoint [1] 302799 0
The samples are stored at room temperature (15-30 degrees Celsius) for testing that will be done within 96 hours.
Secondary outcome [1] 337061 0
To observe the technical success of portal venous sampling.
The samples are stored at room temperature (15-30 degrees Celsius) for testing that will be done within 96 hours. For KRAS mutation analyses, 5 ml of peripheral blood and 5ml of portal venous blood will be collected in tubes designed to stablise the RNA (KRAS seven mutations detection kit).
Timepoint [1] 337061 0
The samples are stored at room temperature (15-30 degrees Celsius) for testing that will be done within 96 hours, and this is when the technical success is determined.
Secondary outcome [2] 337062 0
Observing patient survival. Quantitative variables will be tested by t-test. Univariate analysis for survival will be performed using Kaplan Meier method and differences in Kaplan Meier curves will be tested for statistical significance using the log rank test.
Timepoint [2] 337062 0
Checking medical records over the next 6 months.
Secondary outcome [3] 337063 0
Observing bleeding complications of portal vein cannulation. Blood tests will be done within 24 hours to monitor for any significant decline in haemoglobin.
Timepoint [3] 337063 0
Patients will be monitored for 90 minutes in our recovery unit for complications. Assessed 7 days post procedure via medical records.

Eligibility
Key inclusion criteria
30 patients who are referred to our unit for EUS guided FNA for either suspected (i) metastatic pancreatic cancer; (ii) locally advanced pancreatic cancer or (iii) resectable pancreatic cancer will be recruited for EUS guided portal vein sampling.

i- metastatic pancreatic cancer: imaging evidence of a pancreatic mass with overt discrete lesion(s) in the liver or distant organs.

ii- locally advanced pancreatic cancer: imaging evidence of a pancreatic mass that involved the adjacent organs or vasculatures (SMV, SMA, PV or hepatic artery), without overt evidence of hepatic or distant metastasis.

iii- resectable pancreatic cancer: imaging evidence of an isolate mass in the pancreas without involvement of adjacent organs, vasculatures or distant metastasis.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Coagulopathy or thrombocytopenia.

2. Complete portal vein thrombosis, especially those extending into the hilum and liver.

3. Portal Hypertension (detected via EUS )

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

Recruitment
Recruitment status
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)
SA
Recruitment hospital [1] 8557 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 16661 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 297027 0
Hospital
Name [1] 297027 0
The Royal Adelaide Hospital
Address [1] 297027 0
Department of Gastroenterology and Hepatology,
Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000
Country [1] 297027 0
Australia
Primary sponsor type
Hospital
Name
The Royal Adelaide Hospital
Address
Department of Gastroenterology and Hepatology,
Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000
Country
Australia
Secondary sponsor category [1] 296028 0
None
Name [1] 296028 0
n/a
Address [1] 296028 0
n/a
Country [1] 296028 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298212 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 298212 0
Ethics committee country [1] 298212 0
Date submitted for ethics approval [1] 298212 0
Approval date [1] 298212 0
13/10/2015
Ethics approval number [1] 298212 0
HREC/15/RAH/288

Summary
Brief summary
This study will look at the safety and feasibility of endoscopic ultrasound (EUS) guided portal vein blood sampling as an ultimate staging procedure in patients with pancreatic cancer.
Who is it for?
You may be eligible to join this study if you have been diagnosed with metastatic pancreatic cancer, locally advanced pancreatic cancer, or resectable pancreatic cancer.

Study details
All study participants will undergo endoscopic ultrasound (EUS) guided portal vein blood sampling. EUS is a procedure that safely allows the imaging of the digestive tract and surrounding tissue through ultrasound testing. The use of EUS is currently the preferred method for sampling pancreatic masses.
The portal vein is a blood vessel that provides blood to the pancreas, and other gastrointestinal organs. Blood samples taken from the portal vein can be used to determine if pancreatic cancer cells are present, providing a useful technique for diagnosing pancreatic cancer. This procedure will involve finding portal vein under EUS guidance, and EUS portal vein sampling is done via a trans-hepatic approach that allows the liver tissue to act as a cushion that seals the needle tract, reducing the risk of bleeding complications.
Blood samples will be analysed to count circulating tumour cells, which can be used for molecular characterisation of pancreatic cancers. A way to detect these is to analyse the % of mutated KRAS; a specific protein found in over 90% of patients with pancreatic cancer.
Unfortunately, techniques cannot reliably detect small numbers of mutant KRAS copies. In peripheral blood samples, there is only a reported sensitivity of approximately 50% in patients with pancreatic cancer. This may be higher in portal venous samples where there is no filtering by the liver.

All participants will also be monitored for safety for up to 7 days post procedure. Final follow-up will occur at 6 months.
It is hoped that EUS guided portal vein blood sampling could represent the most sensitive technique for biological staging in pancreatic cancer.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 76358 0
Dr Vinh-An Huu
Address 76358 0
Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Port Road, Adelaide, SA, 5000
Country 76358 0
Australia
Phone 76358 0
+61 8 7074 2189
Fax 76358 0
Email 76358 0
vinh-anhuu.phan@sa.gov.au
Contact person for public queries
Name 76359 0
Ms Romina Safaeian
Address 76359 0
Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Port Road, Adelaide, SA, 5000
Country 76359 0
Australia
Phone 76359 0
+61 8 7074 2189
Fax 76359 0
Email 76359 0
romina.safaeian@sa.gov.au
Contact person for scientific queries
Name 76360 0
Ms Romina Safaeian
Address 76360 0
Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Port Road, Adelaide, SA, 5000
Country 76360 0
Australia
Phone 76360 0
+61 8 7074 2189
Fax 76360 0
Email 76360 0
romina.safaeian@sa.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
Investigator is undecided whether IPD will be available for this trial
What supporting documents are/will be available?
No other documents available
Summary results
Not applicable