Trial registered on ANZCTR


Trial ID
ACTRN12611001273976
Ethics application status
Approved
Date submitted
9/12/2011
Date registered
12/12/2011
Date last updated
28/07/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessment of the Safety and Efficacy of Intra-Arterial Liver Isolation Chemotherapy Using an Implantable Vascular Access System
Scientific title
Treating patients with colorectal liver metastases or hepatocellular carcinoma with intra-arterial liver isolation chemotherapy delivered through an implantable vascular access system and to determine its feasibility, safety and efficacy.
Secondary ID [1] 273572 0
Nil known
Universal Trial Number (UTN)
U1111-1126-1877
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
1. Secondary hepatic metastases from colorectal cancer
2. Hepatocellular carcinoma
279368 0
Condition category
Condition code
Cancer 285556 285556 0 0
Liver

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 a CTA scan is carried out to determine patient suitability. A baseline PET-CT scan is also performed 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 sytem) 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 can be discharged after recovery.


CHEMOTHERAPY INFUSION PROCEDURE: During the chemotherapy infusion sessions the patient will be ventilated with positive end-expiratory pressure (PEEP) whilst under general anesthesia. Depending on the specific patient anatomy up to 4 catheters will be used to selectively cannulate and obstruct the target visceral vessels. Once the flow to the liver is isolated, a microcatheter will be used via the coeliac trunc to superselectively target a pre-determined liver lesion and subsequently deliver chemotherapy locally for 20-30 minutes. All catheters are removed after the infusion and the patient discharged after recovery. The procedure is expected to take between 60-200 minutes. Depending on the patient response, the patient will be infused 3-8 times over the 30 day course.

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 is discharged after recovery.


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. A PET-CT scan and a QOL Survey will be carried out during the 1 month follow up period.
Intervention code [1] 283872 0
Treatment: surgery
Intervention code [2] 283873 0
Treatment: Devices
Comparator / control treatment
This is a feasibility and safety/efficacy study as there is no comparator/control treatment.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 286116 0
To determine the feasibility of the implantable access port in its ability to facilitate the administration of chemotherapy via intra-arterial liver isolation. Outcome is assessed through evaluation of all the operative reports of the standardised chemotherapy infusion sessions carried out.
Timepoint [1] 286116 0
At every chemotherapy infusion session
Primary outcome [2] 286117 0
To determine the safety and efficacy of intra-arterial liver isolation chemotherapy using the implantable vascular access system. Outcome is assessed through monitoring serious adverse events and adverse events such as significant infection, haematoma/haemorrhage, septicaemia, or significant thrombosis.
Timepoint [2] 286117 0
From implantation to 3 months post-explantation
Secondary outcome [1] 295178 0
To increase the overall survival rate of patients. Assessed by survivorship through post-treatment follow ups.
Timepoint [1] 295178 0
Follow-ups beyond 3 month post-explantation
Secondary outcome [2] 295179 0
To increase the patient's response rate to the chemotherapy. Assessed by resectability of tumour post-treatment and changes in tumour size.
Timepoint [2] 295179 0
Baseline PET-CT and ultrasound of the liver and at 1 month post-explantation
Secondary outcome [3] 295180 0
To minimise the systemic side effects of chemotherapy. Assessed through blood samples during the chemotherapy infusion sessions.
Timepoint [3] 295180 0
During chemotherapy infusion sessions
Secondary outcome [4] 295181 0
To improve patient's overall quality of life. Determined through questionnaires.
Timepoint [4] 295181 0
Baseline and 1 month post-explantation

Eligibility
Key inclusion criteria
Colorectal cancer liver metastases patients:
1) Patients must be over 18 years of age
2) Patients must be able to understand the risks and benefits of the trial and give written informed consent to participate
3) Patients must be fit for anaesthesia
4) Patients must have histologically proven colorectal cancer
5) Patients have unresectable hepatic metastases
6) Patient has failed first line therapy
7) Patients' World Health Organization performance status less than or equal to 2
8) Patients have adequate bone marrow
9) Patients have adequate renal function
10) Patients have adequate liver function
11) Patients have normal coagulation

Hepatocellular carcinoma patients:
1) Patient must be over 18 years of age
2) Patients must be able to understand the risks and benefits of the trial and give written informed consent to participate
3) Patients must be fit for anaesthesia
4) Patients have a Child-Pugh score of A or B
5) Patients have failed 1st line therapy
6) Patients have adequate hematology/bone marrow
7) Patients have adequate liver function
8) Patients have normal coagulation
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Colorectal cancer liver metastases patients:
1) World Health Organization performance status > 2
2) Patients have clinically significant ascites
3) Patients have dominant extra-hepatic disease
4) Technical inability to perform HAI
5) Patients have had previous treatment with SIR spheres
6) Patients have Grade 3 or 4 peripheral neuropathy
7) Patients have significant co-morbidities

Hepatocellular carcinoma patients:
1) Child-Pugh score of C
2) Patients have dominant extra-hepatic disease
3) Patients have had previous treatment with SIR-spheres
4) Technical inability to perform HAI
5) Patients have significant co-morbidities
6) Patients have advanced liver failure/complications

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)
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/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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

Funding & Sponsors
Funding source category [1] 284363 0
Self funded/Unfunded
Name [1] 284363 0
Dr Rodney Lane
Address [1] 284363 0
Suite 13, Greenwich Square 130-134 Pacific Highway St Leonards NSW 2065
Country [1] 284363 0
Australia
Primary sponsor type
Individual
Name
Dr Rodney Lane
Address
Suite 13, Greenwich Square 130-134 Pacific Highway St Leonards NSW 2065
Country
Australia
Secondary sponsor category [1] 283291 0
None
Name [1] 283291 0
Address [1] 283291 0
Country [1] 283291 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286313 0
Macquarie University Human Research Ethics Committee (HREC)
Ethics committee address [1] 286313 0
Research Office
Research Hub, Building C5C East
Macquarie University NSW 2109
Ethics committee country [1] 286313 0
Australia
Date submitted for ethics approval [1] 286313 0
Approval date [1] 286313 0
30/09/2011
Ethics approval number [1] 286313 0
HREC Reference No: 5201100434

Summary
Brief summary
The study will be recruiting patients with colorectal cancer with liver metastases (CRC-LM) or patients with hepatocellular carcinomas (HCC). The inclusion and exclusion criteria for both CRC-LM and HCC patients can be found in the relevant sections.

This study involves the temporary surgical implantation of a large bore access port (a peripheral access system) in the common femoral artery or the subclavian artery. This procedure will take approximately 2 to 3 hours. You will undergo an operation to have the vascular access device implanted prior to receiving chemotherapy treatment sessions. The chemotherapy treatment sessions will subsequently be given as part of the treatment regime determined by the clinical investigator based on clinical observations. Depending on your response, you will be administered with the liver isolation chemotherapy treatment between 3 to 8 times during the month the device is implanted. After you the final chemotherapy treatment and on the same day, you will then undergo a second operation to remove the device.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33518 0
Prof Rodney Lane
Address 33518 0
Suite 13, Greenwich Square, 130-134 Pacific Highway, St Leonards NSW 2065
Country 33518 0
Australia
Phone 33518 0
+61 2 9438 4500
Fax 33518 0
+61 2 9438 4114
Email 33518 0
profrodlane1@gmail.com
Contact person for public queries
Name 16765 0
Prof Rodney Lane
Address 16765 0
Suite 13, Greenwich Square,
130-134 Pacific Highway,
St Leonards NSW 2065
Country 16765 0
Australia
Phone 16765 0
+61 2 9438 4500
Fax 16765 0
+61 2 9438 4114
Email 16765 0
profrodlane1@gmail.com
Contact person for scientific queries
Name 7693 0
Prof Rodney Lane
Address 7693 0
Suite 13, Greenwich Square,
130-134 Pacific Highway,
St Leonards NSW 2065
Country 7693 0
Australia
Phone 7693 0
+61 2 9438 4500
Fax 7693 0
+61 2 9438 4114
Email 7693 0
profrodlane1@gmail.com