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Trial registered on ANZCTR


Registration number
ACTRN12614000452695
Ethics application status
Not yet submitted
Date submitted
9/04/2014
Date registered
1/05/2014
Date last updated
10/07/2019
Date data sharing statement initially provided
10/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Intra-Arterial Isolation Chemotherapy for Locally Advanced Unresectable Pancreatic Cancer
Scientific title
Phase Ib/II Study of Intra-Arterial Isolation Chemotherapy for Locally Advanced Unresectable Pancreatic Adenocarcinoma
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 Adenocarcinoma 290346 0
Condition category
Condition code
Cancer 290743 290743 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The treatment proposed in this clinical investigation plan is to repeatedly administer intra-arterial isolation chemotherapy to locally advanced pancreatic adenocarcinoma when the blood flow to and from the pancreas has been isolated via balloon catheters and positive end-expiratory pressure (PEEP). The objective of this study is to evaluate the tumour response, rates of conversion to resectability, 12-month survival, progression-free survival, quality of life, and treatment morbidity and mortality of repeated and isolated intra-arterial hepatic infusion of gemcitabine + oxaliplatin compared with the gold standards of intravenous gemcitabine, gemcitabine + nab-paclitaxel, and 5-FU/leucovorin/oxaliplatin/irinotecan (FOLFIRINOX) treatment.

The treatment proposed in this study is based on the hypothesis that direct arterial infusion of chemotherapy to tumours in the pancreas whilst the blood flow to the organ is isolated could potentially yield benefits that cannot be achieved with existing treatment regimens.

There are three treatment stages; implantation of a vascular access device (known as the AVAS), intra-arterial chemotherapy infusions, and explantation of the AVAS.

IMPLANTATION: the participant is admitted to hospital and the AVAS is surgically implanted under general anaesthetic. The AVAS is an implantable large bore cannula with one end that can be anastomosed directly onto a peripheral vessel and the opposite end exiting the patient’s skin. The device can be opened to access the patient’s vasculature when required and closed when the device is not in use. In accordance with the manufacturer’s Instructions-For-Use (IFU), the AVAS will be implanted in the axillary artery (i.e. the upper pectoral area) or in the common femoral artery (upper thigh) by a trained vascular surgeon. The implantation procedure takes around 2 hours. After implantation, the participant is monitored overnight.

INTRA-ARTERIAL CHEMOTHERAPY INFUSIONS: the participant is admitted to the angiography suite and under general anaesthetic or conscious sedation, intra-arterial pancreatic isolation chemotherapy infusion is administered by an interventional radiologist. Patients receive up to 12 infusions over an up to 8-week period. The first infusion can be administered 2 days after device implantation, and infusions are spaced such that there are no more than 2 infusions for 10 consecutive day period. Each infusion can take between 2-3 hours during the first few infusions but procedure times shorten (typically down to 1-2 hours as the radiologist becomes familiarised with the patient’s individual vascular anatomy. During the Phase Ib stage, gemcitabine + oxaliplatin will be administered with inter-patient escalation according to the accelerated titration model of dose escalation studies to determine a recommended phase 2 dose (RP2D). The RP2D will be used for all patients enrolled during the Phase II stage.

EXPLANTATION: Device explantation may be performed immediately following the final infusion, or in a separate procedure at a later time depending on the availability of operating rooms and the condition of the participant. The surgical removal of the device takes approximately 1-2 hours, the participant is monitored overnight and discharged the next day.
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
Response Rate (RR) of tumours in pancreas as assessed via CT scans (RECIST criteria)
Timepoint [1] 291875 0
4-6 weeks after final infusion procedure.
Secondary outcome [1] 307719 0
12-Month survival assessed via follow-up visits
Timepoint [1] 307719 0
12 months after final infusion procedure.
Secondary outcome [2] 307720 0
Pancreatic progression-free survival as assessed by CT scans (RECIST criteria)
Timepoint [2] 307720 0
As per standard of care schedule (typically quarterly scans) for 12 months after final infusion.
Secondary outcome [3] 307721 0
Overall progression-free survival as assessed by CT scans (RECIST criteria)
Timepoint [3] 307721 0
As per standard of care schedule (typically quarterly scans) for 12 months after final infusion.
Secondary outcome [4] 307722 0
Quality of life assessed via a combined questionnaire (EORTC QLQ-C30 and QLQ-LMC21).
Timepoint [4] 307722 0
Prior enrolment, after 2 infusions, and 4-6 weeks after final infusion procedure.
Secondary outcome [5] 372443 0
Systemic side effects to chemotherapy assessed by collection of adverse events using Common Terminology Criteria for Adverse Events 4.03.
Timepoint [5] 372443 0
From enrolment until primary outcome is assessed (4-5 weeks after final infusion procedure).
Secondary outcome [6] 372444 0
Organ isolation capability as determined by pressure readings on catheters during infusions procedures
Timepoint [6] 372444 0
At the completion of each infusion procedure
Secondary outcome [7] 372445 0
Conversion to resectable disease, as assessed by patient's oncologist and surgeon.
Timepoint [7] 372445 0
4-6 weeks after last infusion procedure

Eligibility
Key inclusion criteria
1) Patient age = 18 years;
2) Patient must be competent to give consent for treatment, be informed of the possible risks and benefits of the trial, and provide written informed consent to participate;
3) Patient must be fit to undergo surgery for implantation/explantation of the AVAS;
4) Patient must be fit for repeated general anaesthesia as required by the treatment protocol;
5) Histologically proven adenocarcinoma of the pancreas;
6) Pancreatic adenocarcinoma stage confirmed as locally advanced unresectable by pancreatic protocol computed tomography and staging laparoscopy;
7) World Health Organisation (WHO) / Eastern Cooperative Oncology Group (ECOG) score = 2
8) Adequate bone marrow function;
9) Adequate renal function;
10) Adequate liver function;
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Metastatic disease;
2) Previous chemotherapy, radiotherapy, or surgery for pancreatic adenocarcinoma;
3) Evidence of prognostically significant ascites;
4) Evidence of pancreatitis;
5) Patient anatomy incompatible with vascular isolation procedure according to CT-angiography findings;
6) All pancreatic lesions are not measurable (RECIST v1.1) by CT scan during patient screening;
7) Allergy to interventional radiology contrast agents;
8) Allergy or hypersensitivity to chemotherapeutic agents used in study treatment;
9) Patients who are enrolled or intend to participate in another clinical trial for treatment of pancreatic adenocarcinoma concurrent with this study;
10) Significant co-morbidities (i.e. life expectancy = 3 months)
11) Co-morbidities or medical conditions that preclude treatment according to the study protocol without unacceptable risk to patient, or preclude testing according to the study protocol;

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
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Other reasons/comments
Other reasons
Change of Sponsorship and other major protocol changes were necessary.
Date of first participant enrolment
Anticipated
30/06/2018
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
6
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
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
Not yet submitted
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
30/04/2019
Approval date [1] 290849 0
Ethics approval number [1] 290849 0

Summary
Brief summary
AIM:
The aim of this study is to assess the safety, feasibility, and efficacy of using vascular isolation chemotherapy to deliver treatment directly to the pancreas, bypassing the main blood supply throughout the body.

WHO IS IT FOR?
You may be eligible for this study if you are aged over 18 years, have proven locally advanced unresectable adenocarcinoma of the pancreas, and have received no prior systemic chemotherapy.

Study details
Once enrolled, patients will have baseline scans and will have the AVAS device implanted. The patient will be admitted to hospital up to twice per 10 day period to be treated with the pancreas directed therapy until they have received up to 12 treatments of gemcitabine + oxaliplatin, after which the device will be explanted. Gemcitabine is approved in Australia as a chemotherapy treatment for pancreatic cancer. Oxaliplatin is a component of the FOLFIRINOX regimen, which is approved in Australia for the treatment of metastatic pancreatic cancer. Neither agent has been approved for intra-arterial infusion to the pancreas using the study method and AVAS device.The patient’s tumour will be scanned 4-6 weeks after the final infusion, and the patient will be followed up for 12 months.

The treatment proposed in this study is based on the hypothesis that direct arterial infusion of chemotherapy to locally advanced pancreatic adenocarcinoma whilst the blood flow to the organ is isolated could potentially yield benefits that cannot be achieved with existing treatment regimens.
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
[email protected]
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
[email protected]
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
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Trial ceased before any trial site was activated - hence there no patients were ever screened or enrolled. No data to share.


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
No additional documents have been identified.