HAI-Floxuridine, or Liver-Tx, Combined With 2nd Line Chemotherapy Versus 2nd Line Chemotherapy Alone for Patients With Colorectal Liver Metastases and Heavy Tumour Burden.

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 to HAI-floxuridine (FUDR), or liver-Tx, in addition to 2nd line chemotherapy versus 2nd line chemotherapy alone (Excalibur 1) or systemic chemotherapy with HAI/FUDR versus systemic chemotherapy alone (Excalibur 2). Primary endpoint is overall survival at 2yrs.

Timeline

Start

2021-08-23

Primary completion

2025-05

Completion

2026-05

Publications

• Background Pak LM, Kemeny NE, Capanu M, Chou JF, Boucher T, Cercek A, Balachandran VP, Kingham TP, Allen PJ, DeMatteo RP, Jarnagin WR, D'Angelica MI. Prospective phase II trial of combination hepatic artery infusion and systemic chemotherapy for unresectable colorectal liver metastases: Long term results and curative potential. J Surg Oncol. 2018 Mar;117(4):634-643. doi: 10.1002/jso.24898. Epub 2017 Nov 22.
• Background Groot Koerkamp B, Sadot E, Kemeny NE, Gonen M, Leal JN, Allen PJ, Cercek A, DeMatteo RP, Kingham TP, Jarnagin WR, D'Angelica MI. Perioperative Hepatic Arterial Infusion Pump Chemotherapy Is Associated With Longer Survival After Resection of Colorectal Liver Metastases: A Propensity Score Analysis. J Clin Oncol. 2017 Jun 10;35(17):1938-1944. doi: 10.1200/JCO.2016.71.8346. Epub 2017 Apr 20.
• Background D'Angelica MI, Correa-Gallego C, Paty PB, Cercek A, Gewirtz AN, Chou JF, Capanu M, Kingham TP, Fong Y, DeMatteo RP, Allen PJ, Jarnagin WR, Kemeny N. Phase II trial of hepatic artery infusional and systemic chemotherapy for patients with unresectable hepatic metastases from colorectal cancer: conversion to resection and long-term outcomes. Ann Surg. 2015 Feb;261(2):353-60. doi: 10.1097/SLA.0000000000000614.
• Background Dueland S, Foss A, Solheim JM, Hagness M, Line PD. Survival following liver transplantation for liver-only colorectal metastases compared with hepatocellular carcinoma. Br J Surg. 2018 May;105(6):736-742. doi: 10.1002/bjs.10769. Epub 2018 Mar 13.
• Background Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocakova I, Ruff P, Blasinska-Morawiec M, Smakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010 Nov 1;28(31):4697-705. doi: 10.1200/JCO.2009.27.4860. Epub 2010 Oct 4.
• Background Boeckx N, Koukakis R, Op de Beeck K, Rolfo C, Van Camp G, Siena S, Tabernero J, Douillard JY, Andre T, Peeters M. Primary tumor sidedness has an impact on prognosis and treatment outcome in metastatic colorectal cancer: results from two randomized first-line panitumumab studies. Ann Oncol. 2017 Aug 1;28(8):1862-1868. doi: 10.1093/annonc/mdx119.
• Background Van Cutsem E, Kohne CH, Lang I, Folprecht G, Nowacki MP, Cascinu S, Shchepotin I, Maurel J, Cunningham D, Tejpar S, Schlichting M, Zubel A, Celik I, Rougier P, Ciardiello F. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011 May 20;29(15):2011-9. doi: 10.1200/JCO.2010.33.5091. Epub 2011 Apr 18.
• Background Dueland S, Guren TK, Hagness M, Glimelius B, Line PD, Pfeiffer P, Foss A, Tveit KM. Chemotherapy or liver transplantation for nonresectable liver metastases from colorectal cancer? Ann Surg. 2015 May;261(5):956-60. doi: 10.1097/SLA.0000000000000786.
• Background Giacchetti S, Itzhaki M, Gruia G, Adam R, Zidani R, Kunstlinger F, Brienza S, Alafaci E, Bertheault-Cvitkovic F, Jasmin C, Reynes M, Bismuth H, Misset JL, Levi F. Long-term survival of patients with unresectable colorectal cancer liver metastases following infusional chemotherapy with 5-fluorouracil, leucovorin, oxaliplatin and surgery. Ann Oncol. 1999 Jun;10(6):663-9. doi: 10.1023/a:1008347829017.
• Background Brudvik KW, Bains SJ, Seeberg LT, Labori KJ, Waage A, Tasken K, Aandahl EM, Bjornbeth BA. Aggressive treatment of patients with metastatic colorectal cancer increases survival: a scandinavian single-center experience. HPB Surg. 2013;2013:727095. doi: 10.1155/2013/727095. Epub 2013 Jun 6.
• Background Zakaria S, Donohue JH, Que FG, Farnell MB, Schleck CD, Ilstrup DM, Nagorney DM. Hepatic resection for colorectal metastases: value for risk scoring systems? Ann Surg. 2007 Aug;246(2):183-91. doi: 10.1097/SLA.0b013e3180603039.
• Background Brudvik KW, Jones RP, Giuliante F, Shindoh J, Passot G, Chung MH, Song J, Li L, Dagenborg VJ, Fretland AA, Rosok B, De Rose AM, Ardito F, Edwin B, Panettieri E, Larocca LM, Yamashita S, Conrad C, Aloia TA, Poston GJ, Bjornbeth BA, Vauthey JN. RAS Mutation Clinical Risk Score to Predict Survival After Resection of Colorectal Liver Metastases. Ann Surg. 2019 Jan;269(1):120-126. doi: 10.1097/SLA.0000000000002319.
• Background Day RW, Brudvik KW, Vauthey JN, Conrad C, Gottumukkala V, Chun YS, Katz MH, Fleming JB, Lee JE, Aloia TA. Advances in hepatectomy technique: Toward zero transfusions in the modern era of liver surgery. Surgery. 2016 Mar;159(3):793-801. doi: 10.1016/j.surg.2015.10.006. Epub 2015 Nov 14.

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