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Study of Intra-Arterial Oxaliplatin Plus Capecitabine to Treat Liver Metastases From Colorectal Cancer (SYS-CAPLIOX)

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ClinicalTrials.gov Identifier: NCT04701281
Recruitment Status : Recruiting
First Posted : January 8, 2021
Last Update Posted : March 15, 2022
Sponsor:
Information provided by (Responsible Party):
AllVascular

Brief Summary:
The treatment proposed in this trial is to administer intra-arterial chemotherapy to liver metastases from colorectal cancer when the blood flow to and from the liver has been isolated via balloon catheters through a vascular access system called the AVAS. The objective of this study is to evaluate the tumour response of repeated and isolated intra-arterial liver isolation oxaliplatin compared with the standard systemic chemotherapy (intravenous 5-FU + leucovorin + oxaliplatin [FOLFOX] or oral capecitabine with IV oxaliplatin [XELOX]).

Condition or disease Intervention/treatment Phase
Liver Metastasis Colon Cancer Combination Product: Intra-arterial LIOX + Capecitabine Phase 1 Phase 2

Detailed Description:

The treatment proposed in this study is based on the hypothesis that direct arterial infusion of chemotherapy to metastatic tumours of the liver 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 liver isolation oxaliplatin (LIOX) 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 surgeon experienced in vascular disease. The implantation procedure takes around 2 hours. After implantation, the participant is monitored overnight.

Intra-arterial LIOX infusions: the participant is admitted to the angiography suite and under general anaesthetic or conscious sedation, intra-arterial hepatic isolation chemotherapy infusion is administered by an interventional radiologist. The first infusion can be administered 2 days after device implantation and infusions are spread out over an 8-week period at a maximum such that the patient receives 5 to 7 infusions in total, has at least 2 full calendar days between each infusion, and there are no more than 2 infusions over any 7 consecutive days. Each infusion can take between 2-3 hours during the first few infusions but should only take 1-2 hours for the remaining infusions as the radiologist becomes familiarised with the patient's vascular anatomy.

During the Phase Ib stage, the starting dose of the oxaliplatin infused will be 50mg/m^2 and this dose will be escalated by 10mg/m^2 with each patient until an optimal dose is established. The optimal dose will be used for all patients enrolled during the Phase II stage.

Explantation: the final infusion session is followed by the device explantation immediately, or 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.

In addition, capecitabine will be administered orally as per standard care (1000 mg/m^2 twice daily in 2 week cycles) throughout the study treatment period (from enrolment to 4 weeks after the AVAS explantation) as a form of systemic disease management. The oncologist may modify the capecitabine dose/frequency based on the patient's response to the medication.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 95 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Single arm, two cohorts:

Cohort 1: 1st line patients, RAS mutant; Cohort 2: pre-treated or refractory patients, no specific mutation

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib/II Study of Intra-Arterial Liver Isolation Chemotherapy in Patients With Hepatic Metastases From Colorectal Cancer
Actual Study Start Date : June 20, 2019
Estimated Primary Completion Date : July 31, 2023
Estimated Study Completion Date : July 31, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Intra-arterial LIOX + Capecitabine
5 - 7 LIOX (liver isolation oxaliplatin) intra-arterial infusions over 8 weeks + capecitabine
Combination Product: Intra-arterial LIOX + Capecitabine
5 - 7 LIOX (liver isolation oxaliplatin) intra-arterial infusions over 8 weeks + capecitabine




Primary Outcome Measures :
  1. Liver-specific response rate (RR) [ Time Frame: 4 weeks post explantation of AVAS; ]
    Assessed via clinical imaging and tumour markers using RECIST v1.1;


Secondary Outcome Measures :
  1. Two-year survival rate; [ Time Frame: 3, 6, 9, 12, 18 and 24 months post end of treatment and AVAS explantation; ]
    During follow-up;

  2. Progression free survival (PFS); [ Time Frame: 3, 6, 9, 12, 18 and 24 months post end of treatment and AVAS explantation; ]
    During follow-up;

  3. Systemic side effects to chemotherapy [ Time Frame: From enrolment until primary outcome is assessed (4 weeks post AVAS explantation); ]
    Assessed by collection of adverse events using Common Terminology Criteria for Adverse Events (CTCAE v5.0);

  4. Organ isolation capability [ Time Frame: Measured after each infusion treatment, through study completion, up to 8 weeks; ]
    Determined by pressure readings on catheters;

  5. Conversion to resection rate; [ Time Frame: Assessed at end of treatment, 4 weeks post AVAS explanation; ]
  6. Health-related Quality of life (QoL); [ Time Frame: Through study completion, an average of 8 weeks; ]
    Assessed via EORTC Quality of Life Questionnaire C30: comprising 28 lifestyle and health questions using a four point scale (not at all, a little, quite a bit, very much) and 2 questions measuring overall health and overall quality of life on a visual analogue scale (1 very poor - 7 excellent);

  7. Health-related Quality of life (QoL); [ Time Frame: Through study completion, an average of 8 weeks; ]
    Assessed via EORTC Quality of Life Questionnaire LMC21: comprising 10 digestion and and health questions using a four point scale (not at all, a little, quite a bit, very much);



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males or females, aged 18 years or older, with hepatic metastases from histologically proven adenocarcinoma of the colon/rectum;
  2. Limited extrahepatic metastases in the lung or lymph nodes;
  3. Confirmed non-progressive disease in the liver, per RECIST v1.1, halfway into the first-line systemic chemotherapy regimen after a minimum of 4 cycles of FOLFOX/XELOX ± monoclonal antibodies OR liver-dominant pre-treated or refractory patients;
  4. Genotype: RAS mutant for first line patients only. All genetic mutations allowable for pre-treated or refractory patients;
  5. Prior treatment with monoclonal antibody treatment is ≥ 4 weeks before implantation;
  6. Considered medically fit for repeated general anaesthesia;
  7. ECOG performance status 0-1;
  8. Adequate bone marrow function (within 14 days of enrolment):

    Haemoglobin ≥ 100 g/L; ANC ≥ 1.5 × 10^9/L; Platelet Count ≥ 100 × 10^9/L;

  9. Adequate renal function (within 14 days of enrolment):

    Serum Creatinine ≤ 1.5 × Upper Limit of Normal;

  10. Adequate liver function (within 14 days of enrolment):

    Bilirubin ≤2.0 × Upper Limit of Normal; AST ≤ 5 × Upper Limit of Normal;

  11. Normal coagulation (within 14 days of enrolment):

    INR ≤ 1.5;

  12. Able to understand the risks and benefits of the study and provide signed, written informed consent to participate;
  13. Willing and able to comply with all study requirements and assessments;

Exclusion Criteria:

  1. CT-angiogram confirms unsuitable vascular anatomy;
  2. No measurable liver disease per RECIST v1.1;
  3. Evidence of ascites, cirrhosis, portal hypertension, main portal venous tumour involvement or main portal venous thrombosis;
  4. Allergies to contrast agents;
  5. Previous hypersensitivity or laryngo-pharyngeal dysaesthesia associated with oxaliplatin;
  6. Previous allergies associated with 5-FU or oxaliplatin;
  7. Grade > 2 peripheral neuropathy (CTCAE 5.0);
  8. Significant co-morbidities;
  9. Life expectancy ≤ 3 months;
  10. Pregnant or breastfeeding women, or women of childbearing potential and men who are not on a reliable form of birth control or barrier method of contraception;
  11. Enrolled or intend to participate in another clinical trial (of an investigational drug or device, new indication for an approved drug or device, or requirement of additional testing beyond standard clinical practice) during this clinical study;
  12. Medical conditions that preclude the testing required by the protocol, or limit study participation;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04701281


Contacts
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Contact: Sharon Sampath +61 02 9438 5228 trials@allvascular.com

Locations
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Australia, New South Wales
Lake Macquarie Private Hospital Recruiting
Gateshead, New South Wales, Australia, 2290
Contact: Hollie Ritchie    +61 02 4947 5799    RitchieH@ramsayhealth.com.au   
Principal Investigator: Stephen Ackland         
GenesisCare, St Leonards Recruiting
Saint Leonards, New South Wales, Australia, 2065
Contact: Ka Yuk Tsui    +61 2 8037 4140    kayuk.tsui@genesiscare.com   
Principal Investigator: Stephen Clarke         
Sydney Adventist Hospital Recruiting
Sydney, New South Wales, Australia, 2076
Contact: Nina Singh    +61 02 9480 6280    Nina.Singh@sah.org.au   
Principal Investigator: Gavin Marx         
Sydney Southwest Private Hospital Recruiting
Sydney, New South Wales, Australia, 2170
Contact: Win Hlaing    +61 02 8738 9162    Win.Hlaing@health.nsw.gov.au   
Principal Investigator: Aflah Roohullah         
Australia, Queensland
Gold Coast Private Hospital Recruiting
Southport, Queensland, Australia, 4215
Contact: Michelle Cestari    0429 116 951    michelle.cestari@healthscope.com.au   
Principal Investigator: Marco Matos         
Principal Investigator: Andrea Tazbirkova         
Sponsors and Collaborators
AllVascular
Investigators
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Study Chair: Nick Pavlakis, A/Prof GenesisCare, St Leonards
Additional Information:
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Responsible Party: AllVascular
ClinicalTrials.gov Identifier: NCT04701281    
Other Study ID Numbers: SYS-CAPLIOX
First Posted: January 8, 2021    Key Record Dates
Last Update Posted: March 15, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AllVascular:
liver
metastases
colon
rectal
intra-arterial
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplasms
Neoplastic Processes
Pathologic Processes
Capecitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents