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
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Cancer Liver Metastases Chemotherapy Effect||Drug: Floxuridine Procedure: Liver Transplantation||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||45 participants|
|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)|
|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|
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.
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
- 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
- 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
- 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.
- 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.
- 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
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