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Trial record 1 of 1 for:    NCT04898504
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HAI-Floxuridine, or Liver-Tx, Combined With 2nd Line Chemotherapy Versus 2nd Line Chemotherapy Alone for Patients With Colorectal Livermetasteses and Heavy Tumour Burden. (EXCALIBUR1+2)

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ClinicalTrials.gov Identifier: NCT04898504
Recruitment Status : Recruiting
First Posted : May 24, 2021
Last Update Posted : July 7, 2021
Sponsor:
Information provided by (Responsible Party):
John Christian Fischer Glent, MD, Oslo University Hospital

Brief Summary:
Patients with colorectal livermetasteses and heavy tumour burden and progression on 1st line chemotherapy have no other available treatment in Norway today other than 2nd line chemotherapy. The Investigators will randomize patients younger than 70 yrs old to HAI-floxuridine, or liver-Tx, in addition to 2nd line chemotherapy versus 2nd line chemotherapy alone. Patients 70yrs and older will be randomized to HAI-floxuridine and 2nd line chemotherapy versus 2nd line chemotherapy alone. Primary endpoint being overall survival at 2yrs in the different arms.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Liver Metastases Chemotherapy Effect Drug: Floxuridine Procedure: Liver Transplantation Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 3 armed parallel RCT randomizing between 2nd line chemotherapy + HAI-floxuridine or liver-Tx versus 2nd line chemotherapy alone. Making it 3 arms, HAI, liver-Tx, 2nd line chemotherpy alone (current standard)
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: EXtended CriteriA Treatment for LIver Metastases With Heavy Tumour BURden 1 + 2
Estimated Study Start Date : August 2021
Estimated Primary Completion Date : May 2024
Estimated Study Completion Date : May 2026

Resource links provided by the National Library of Medicine

Drug Information available for: Floxuridine

Arm Intervention/treatment
No Intervention: 2nd line chemotherapy
2nd line chemotherapy is the current standard treatment for patients with CRLM and progression on 1st line chemotherapy. We will include 18 patients in this treatment arm thus empowering the study to show non-inferiority between HAI and 2nd line chemo.
Active Comparator: Liver transplant
Liver transplantation (LTX) has emerged as a possible solution for some patients with unresectable CRLM who otherwise have good prognosis based on available scorings systems. We will include 9 patients in this treatment arm. They will be given 2nd line chemotherapy followed by Liver-Tx. Including 9 patients will only empower the study to show non-inferiority between Liver-Tx and 2nd line chemo (where we expect a large difference in the primary end-point) but not between HAI and Liver-Tx.
Procedure: Liver Transplantation
Patients randomized to this arm will be given 2nd line chemotherapy (regimen given at the discression of the treating oncologist) followed by liver-Tx

Active Comparator: Hepatic artery infusion (HAI) chemotherapy
The biological rationale for intra-arterial chemotherapy is that the hepatic artery rather than the portal vein is responsible for most of the blood supply to liver tumors. Floxuridine has for years been established as viable treatment option for similar patients at The Memorial Sloan Kettering Cancer Institute, New York, but has yet to gain foothold in Europe despite promising results. We will include 18 patients in this arm receiving 6 cycles of HAI-Floxuridine and a full course of 2nd line chemotherapy.
Drug: Floxuridine
A laparotomy will be performed and a catheter placed in the hepatic artery Connected to a subcutaneous pump. This pump will be percutaneously filled with Floxuridine 6 times in 2 weeks cycles, alternating with heparin-solution.
Other Name: Hepatic artery Infusion Chemotherapy




Primary Outcome Measures :
  1. Overall survival at 2 years [ Time Frame: 2 years ]
    Patients with colorectal livermetasteses and insufficient respons on 1st line chemotherapy have a current OS of 14months from starting 2nd line chemotherapy. We want to see if any of or other treatment-arms will provide for a longer OS for these patients


Secondary Outcome Measures :
  1. Quality of Life by using QLQ-C30 [ Time Frame: At inclusion, and weeks, 6,12,24,36 and every 12 weeks until death or other illness-related incident. ]
    We will investigate the QuOL regularly by using QLQ-C30 verified Norwegian editions

  2. Operative complications [ Time Frame: Withion 30 days after surgery ]
    Both liver-Tx and HAI-pump implantation are procedures and thus at risk for operative, and postoperative, complications. We will investigate major postoperative complications defined as Clavien-Dindo Score > 3b.

  3. Postoperative morbidity and mortality [ Time Frame: 30 and 90 days after surgery ]
    Both liver-Tx and HAI-pump implantation are procedures and thus at risk for operative, and postoperative, complications. We will investigate major postoperative complications defined as Clavien-Dindo Score > 3b.

  4. Quality of life using EQ-5D-5L [ Time Frame: At inclusion, and weeks, 6,12,24,36 and every 12 weeks until death or other illness-related incident. ]
    We will investigate the QuOL regularly by using EQ-5D-5L verified Norwegian editions



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 Excalibur 1 and 2

Included patients must fulfil the following criteria

  1. Primary histology:

    a. Verified adenocarcinoma in colon/rectum, radically resected with adequate margins/pre-operative treatment

  2. Liver metastases:

    a. Six or more liver metastases that have progression (or insufficient response on 1st line chemotherapy, including toxicity). and are hence planned for 2nd line chemotherapy

  3. If a history of confirmed extra hepatic metastatic lesion or local relapse, this must have been successfully treated more than 2 years ago without a new relapse.
  4. Chemotherapy

    1. Planned for 2nd line chemotherapy.
    2. If patients are switched to 2nd line chemotherapy, randomization can only be allowed prior to first evaluation on 2nd line chemotherapy regimen.
  5. The patient

    1. Good performance status, ECOG 0 or 1.
    2. Satisfactory blood tests: Hb >10g/dl, neutrophiles >1.0 (after any G-CSF), TRC >75, Bilirubin<1.5 x upper normal level, ASAT, ALAT<5 x upper normal level, Creatinine <1.25 x upper normal level. Albumin above lower normal level.
    3. Women of childbearing potential (WOCBP) must have a confirmed menstrual cycle and a negative highly sensitive pregnancy test prior to inclusion, or two negative pregnancy tests two weeks apart
    4. WOCBP must agree to use a highly effective method of contraception (see section 6.1.2) for the entire period of exposure to the IMP in the trial, plus for one menstrual cycle/30 days after the last exposure due to the genotoxic potential of the IMP
    5. Men that may have sexual relations with a WOCBP during the trial must agree to use a condom during intercourse for the entire period of exposure plus for one sperm cycle / 90 days after the last exposure due to the genotoxic potential of the IMP
  6. Signed informed consent and expected cooperation of the patients for treatment and follow up must be obtained and documented according to GCP, and national/local regulations.

Exclusion Criteria Excalibur 1 and 2

Any of the following criteria will exclude participation in the trial:

  1. Arterial anatomy not suited for HAI pump-line insertion.
  2. Liver metastatic ingrowth to the diaphragm determined by CT-scan and/or MRI/or ultrasound
  3. Previous bone or CNS metastatic disease.
  4. Non-curable pulmonary or peritoneal metastases, non-regional lymph-nodes, or local recurrence on PET/CT scan, and on CT or MRI thorax/abdomen/pelvis dated within 6 weeks prior to the trial hospital MDT meeting.
  5. Patients with known intolerance or allergy to any ingredient of the IMP to be used as standard therapy for that patient must be excluded
  6. Breastfeeding women must be excluded
  7. Patients with a psychiatric condition that makes participation in the trial impossible or unethical
  8. Patients in a poor nutritional state, those with depressed bone marrow function or those with potentially serious infections must be excluded.
  9. Any other reason why, in the opinion of the investigators, the patient should not participate.

Exclusion Excalibur 1

  1. Any of the following will preclude inclusion into Excalibur 1 (but not into Excalibur 2)
  2. BRAF positivity
  3. Any sign of extra-hepatic metastatic disease or local recurrence on PET/CT scan, and on CT or MRI thorax/abdomen/pelvis dated within 6 weeks prior to the trial hospital MDT meeting (exception allowed for <3 resectable lung lesions all < 15mm).
  4. Liver lesion >10cm
  5. Patient BMI > 30
  6. Any previous non colorectal malignancy within latest five years
  7. Age > 70 years

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): NCT04898504


Locations
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Norway
Oslo University Hospital Recruiting
Oslo, Norway, 0424
Contact: John Ch Glent, MD    92214992 ext +47    uxgloh@ous-hf.no   
Contact: Kristoffer Lassen, MD PhD    47616906 ext +47    krlass@ous-hf.no   
Sponsors and Collaborators
Oslo University Hospital
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Responsible Party: John Christian Fischer Glent, MD, Principal Investigator, Oslo University Hospital
ClinicalTrials.gov Identifier: NCT04898504    
Other Study ID Numbers: 33572
First Posted: May 24, 2021    Key Record Dates
Last Update Posted: July 7, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by John Christian Fischer Glent, MD, Oslo University Hospital:
HAI-floxuridine
2nd line chemotherapy
Liver-Tx
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplasms
Neoplastic Processes
Pathologic Processes
Floxuridine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents