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Trial registered on ANZCTR


Registration number
ACTRN12614000452695
Ethics application status
Approved
Date submitted
9/04/2014
Date registered
1/05/2014
Date last updated
31/07/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessment of Safety and Efficacy of Repeated Intra-Arterial Pancreatic Isolation Chemotherapy
Scientific title
Treating patients with locally advanced unresectable pancreatic carcinoma with intra-arterial pancreatic isolation chemotherapy delivered through an implantable vascular access system and to determine its feasibility, safety and efficacy.
Secondary ID [1] 283434 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally advanced unresectable pancreatic carcinoma 290346 0
Condition category
Condition code
Cancer 290743 290743 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
SCREENING & WORK UP: The patient is screened by the trial staff and a comprehensive patient history is recorded. Baseline blood tests and imaging (PET-CT, CTA scan, guided ultrasonography, and or MRI) is carried out to determine patient suitability and to determine treatment lesions. A Quality of Life (QOL) Survey will be filled in by the patient at this time also.

DEVICE IMPLANTATION PROCEDURE: The procedure involves the surgical implantation under general anaesthetic of a large bore temporary access port (a peripheral access system) in either the common femoral artery or the subclavian artery. The device is implanted by anastomosing the ePTFE graft skirt of the device onto the patient's common femoral artery and tunnelling the tubing of the device through the patient's subcutaneous tissue in the upper thigh/pectoralis and out through the skin. The implantation procedure can take between 1-3 hours and the patient will be monitored overnight and discharged the following day.


CHEMOTHERAPY INFUSION PROCEDURE: During the chemotherapy infusion sessions the patient will be ventilated with positive end-expiratory pressure (PEEP) whilst under general anesthesia. A large duodenal balloon catheter will be introduced intraorally up to the entrance to the jejunum. Depending on the patient's anatomy, up to 4 balloon catheters will be used introduced via the implanted peripheral access system to selectively cannulate and obstruct the arteries supplying blood to the pancreas. Once all catheters are in place, a microcatheter will be introduced to into the appropriate pancreaticoduodenal artery or distal pancreatic artery. All balloon catheters are deployed to isolate the flow, and the duodenal balloon deployed to protect the duodenal mucosa before chemotherapy is infused through the microcatheter. All balloons catheters and the duodenal balloon are deflated and removed after 20 minutes. The procedure is expected to take between 60-200 minutes. The patient may be discharged on the same day after recovery after being assessed by a study clinician. Depending on the patient response, the patient will be infused 6-8 times over the 29 day course.

DOSAGE REGIMEN: Patients 1 & 2 - Esclalating oxaliplatin (5, 10, 20, 40 mg/m^2 for the 1st, 2nd, 3rd, and 4th infusions respectively; 50 mg/m^2 for 5th & 6th infusion; 7th & 8th infusion dose determined from response to previous doses). Patient 3 & 4 - Fixed oxaliplatin (50 mg/m^2) for all 6-8 infusions. Patient 5 & 6 - fixed oxaliplatin (50 mg/m^2) and gemcitabine (250 mg/m^2) for all 6-8 infusions.

INFUSION SCHEDULE: Typically infusions will take place twice a week for the 29 day period with the 1st infusion scheduled for a Monday or Tuesday and the 2nd infusion scheduled for a Thursday or Friday of each week.

DEVICE EXPLANTATION PROCEDURE: After the final chemotherapy infusion, and on the same day, the patient undergoes an explantation procedure where the implanted access device is removed and the vessel sutured either with or without a patch angioplasty. This procedure takes approximately 1-2 hours and the patient monitored overnight to be discharged the following day.

FOLLOW UP PROCEDURE: The trial staff will follow up on the progress of the patient at 1 week, 1 month, 3 months, and 6 months from the date of the explantation procedure. Imaging (PET-CT, guided ultrasonography, and or MRI) will be carried out and a QOL Survey will be carried out during the 1 month follow up period.
Intervention code [1] 289145 0
Treatment: Devices
Intervention code [2] 289146 0
Treatment: Drugs
Intervention code [3] 289180 0
Treatment: Surgery
Comparator / control treatment
There are no comparator/control treatments as this is a feasibility and safety study.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 291875 0
Feasibility - functionality of the device and its ability to facilitate the infusion treatments as assessed by radiologist's operation report (assessing ability to cannulate, isolate, and administer chemotherapy).
Timepoint [1] 291875 0
At every chemotherapy infusion session.
Primary outcome [2] 291876 0
Safety - device related complications (e.g. duodenal balloon malfunction, haemoreduction valve seal tear/leak, anastomotic leak, etc.) as assessed by analysing all reported adverse events. Each device complication will be assessed by the investigators as to whether the incident was serious and anticipated, and reported as per ICH/GCP and TGA guidelines.
Timepoint [2] 291876 0
From device implantation to 6 months post-explantation.
Primary outcome [3] 291877 0
Safety - treatment related complications (e.g. severe side effects of systemic toxicity, local pain, vessel wall trauma, etc.) as assessed by analysing all reported adverse events and radiologist's operation report. Each treatment related complication will be assessed by the investigators as to whether the incident was serious and anticipated, and reported as per ICH/GCP and TGA guidelines.
Timepoint [3] 291877 0
At every chemotherapy infusion session.
Secondary outcome [1] 307719 0
Improve overall survival as assessed by patient survival.
Timepoint [1] 307719 0
At 6 month post-explantation and continuous follow up for up to 1 year post-explantation.
Secondary outcome [2] 307720 0
Improve response rate as assessed through tumour markers and imaging of pancreas.
Timepoint [2] 307720 0
1 month post-explantation.
Secondary outcome [3] 307721 0
Reduce systemic side effects as measured through local and systemic chemotherapy concentrations in haematological samples.
Timepoint [3] 307721 0
During chemotherapy regimen (i.e. between device implantation and device explantation) approximately twice weekly.
Secondary outcome [4] 307722 0
Improve quality of life as measured through QOL surveys (EORTC QLQ-C30).
Timepoint [4] 307722 0
1 month post-explantation.

Eligibility
Key inclusion criteria
1) Patients must be able to understand the risks and benefits of the trial and give written informed consent to participate
2) Patients must be fit for anaesthesia
3) Proven cancer of the pancreas (biochemical evidence or biopsy)
4) Patient has already failed their 1st line treatment
5) World Health Organization performance status less than or equal to 2
6) Adequate bone marrow
7) Adequate renal function
8) Adequate liver function
9) Normal coagulation
10) No significant pancreatitis
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) World Health Organization performance status > 2
2) Dominant extra-pancreatic disease
3) Clinically significant ascites
4) Gastric bypass
5) Technical inability to perform isolation
6) Grade 3 or 4 peripheral neuropathy
7) Significant co-morbidities

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)
Not a randomised trial - allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety
Statistical methods / analysis

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)
NSW
Recruitment hospital [1] 2304 0
Macquarie University Hospital - Macquarie Park
Recruitment postcode(s) [1] 7973 0
2109 - Macquarie University

Funding & Sponsors
Funding source category [1] 289053 0
Self funded/Unfunded
Name [1] 289053 0
Professor Rodney J Lane
Address [1] 289053 0
Suite 13, Greenwich Square 130-134 Pacific Highway St Leonards NSW 2065
Country [1] 289053 0
Australia
Primary sponsor type
Individual
Name
Professor Rodney J Lane
Address
Suite 13, Greenwich Square 130-134 Pacific Highway St Leonards NSW 2065
Country
Australia
Secondary sponsor category [1] 287721 0
None
Name [1] 287721 0
Address [1] 287721 0
Country [1] 287721 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290849 0
Macquarie University Human Research Ethics Commitee
Ethics committee address [1] 290849 0
Research Office
C5C Research HUB East, Level 3, Room 324
Macquarie University NSW 2109 AUSTRALIA
Ethics committee country [1] 290849 0
Australia
Date submitted for ethics approval [1] 290849 0
13/03/2014
Approval date [1] 290849 0
27/03/2014
Ethics approval number [1] 290849 0
Protocol No: 5201300895

Summary
Brief summary
AIM
The aim of the study is to assess the safety and feasibility of administering repeated isolated chemotherapy to cancers of the pancreas that cannot be surgically resected or responsive to traditional chemotherapy.

WHO IS IT FOR
You may be eligible to join this study if you aged 18 years or more and have proven cancer of the pancreas, for which first line treatment has failed. You must be able to understand the risks and benefits of the study and give written informed consent to participate.

STUDY DETAILS
All participants in this study will undergo:
1. Device implantation procedure: A device used to deliver chemotherapy to the pancreas will be implanted under general anaesthesia. The surgical procedure will take between 1-3 hours.
2. Chemotherapy infusion procedure: This involves 6-8 chemotherapy infusion sessions via the device over a 29 day course.
3. Device explantation procedure: After the final chemotherapy infusion, the implanted device will be removed. This procedure takes approximately 1-2 hours.
4. Participants will be monitored throughout treatment and will be followed up at 1 week, 1 month, 3 months, and 6 months from the date of the explantation procedure. They will undergo imaging procedures and asked to carry out a quality of life questionnaire.

HYPOTHESIS
Cancers that are not responsive to normal intravenous chemotherapy require a higher dose. However, this dose would normally be lethal to the patient if delivered intravenously. Hence, isolated chemotherapy treatment (i.e. contained to the pancreas using the access device) could potentially achieve a response from the cancer without excessively harming the patient.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 43782 0
Prof Rodney J Lane
Address 43782 0
Suite 13, Greenwich Square, 130-134 Pacific Highway, St Leonards NSW 2065
Country 43782 0
Australia
Phone 43782 0
+61294384500
Fax 43782 0
+61294384114
Email 43782 0
rjlane47@gmail.com
Contact person for public queries
Name 43783 0
Prof Rodney J Lane
Address 43783 0
Suite 13, Greenwich Square, 130-134 Pacific Highway, St Leonards NSW 2065
Country 43783 0
Australia
Phone 43783 0
+61294384500
Fax 43783 0
+61294384114
Email 43783 0
rjlane47@gmail.com
Contact person for scientific queries
Name 43784 0
Prof Rodney J Lane
Address 43784 0
Suite 13, Greenwich Square, 130-134 Pacific Highway, St Leonards NSW 2065
Country 43784 0
Australia
Phone 43784 0
+61294384500
Fax 43784 0
+61294384114
Email 43784 0
rjlane47@gmail.com

No data has been provided for results reporting
Summary results
Not applicable