Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Metastasis | Study protocol

Hepatic arterial infusion in combination with systemic chemotherapy in patients with hepatic metastasis from colorectal cancer: a randomized phase II study – (NCT05103020) – study protocol

Authors: Ji Su Kim, Hyunwook Kim, Seo Young Lee, Yoon Dae Han, Kichang Han, Byung Soh Min, Man-Deuk Kim, Jong Yun Won, Seung-Hoon Beom, Sang Joon Shin, Han Sang Kim, Dai Hoon Han, Joong Bae Ahn

Published in: BMC Cancer | Issue 1/2023

Login to get access

Abstract

Background

Although 80% of patients with metastatic colorectal cancer (CRC) experience liver metastases, only 10–25% undergo resection at the time of diagnosis. Even in initially unresectable conditions, if appropriate treatment is provided, such as surgical conversion through a combination of hepatic arterial infusion (HAI) chemotherapy and systemic chemotherapy (sys-CT), better overall survival can be expected. Therefore, this study aims to evaluate the efficacy of HAI oxaliplatin in combination with sys-CT plus targeted therapy in patients with unresectable CRC with liver-only metastasis.

Methods

This is a single-center, randomized, open-label phase II trial (NCT05103020). Patients with untreated CRC, who have liver-only metastases and for whom liver resection is potentially possible but deemed infeasible at the time of initial diagnosis by a multidisciplinary team, will be eligible. Patients will be randomly assigned in a 1:1 ratio to either the combined HAI oxaliplatin and modified systemic 5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) plus targeted therapy group or the systemic FOLFIRI plus targeted therapy group. Both regimens will be repeated every 2 weeks for a total of 12 cycles. The primary objective of this study is to compare the rate of conversion to liver resection. The surgical conversion rate is expected to increase by 25% with HAI oxaliplatin in combination with sys-CT plus targeted therapy (40% in the experimental arm versus 15% in the control arm) (power, 80%; two-sided alpha-risk, 5%). The secondary objectives include overall survival, progression-free survival, and objective response rate.

Discussion

This is the first randomized controlled trial to investigate the efficacy of HAI oxaliplatin in combination with sys-CT plus targeted therapy as first-line treatment from the initial diagnosis in patients with unresectable CRC with liver-only metastasis, aiming to significantly increase the surgical conversion rate.

Trial registration

ClinicalTrials.gov, (NCT05103020). Trial registration date: November 2, 2021.
Literature
1.
Scheele J, Stang R, Altendorf-Hofmann A, Paul M. Resection of colorectal liver metastases. World J Surg. 1995;19(1):59–71.CrossRefPubMed
2.
Altendorf-Hofmann A, Scheele J. A critical review of the major indicators of prognosis after resection of hepatic metastases from colorectal carcinoma. Surg Oncol Clin N Am. 2003;12(1):165–92 xi.CrossRefPubMed
3.
Bismuth H, Adam R, Lévi F, Farabos C, Waechter F, Castaing D, Majno P, Engerran L. Resection of nonresectable liver metastases from colorectal cancer after neoadjuvant chemotherapy. Ann Surg. 1996;224(4):509–20 discussion 520–502.CrossRefPubMedPubMedCentral
4.
Devaud N, Kanji ZS, Dhani N, Grant RC, Shoushtari H, Serrano PE, Nanji S, Greig PD, McGilvray I, Moulton CA, et al. Liver resection after chemotherapy and tumour downsizing in patients with initially unresectable colorectal cancer liver metastases. HPB (Oxford). 2014;16(5):475–80.CrossRefPubMed
5.
Tomlinson JS, Jarnagin WR, Dematteo RP, Fong Y, Kornprat P, Gonen M, Kemeny N, Brennan MF, Blumgart LH, D’Angelica M. Actual 10-Year Survival After Resection of Colorectal Liver Metastases Defines Cure. J Clin Oncol. 2007;25(29):4575–80.CrossRefPubMed
6.
De Haas RJ, Wicherts DA, Salloum C, Andreani P, Sotirov D, Adam R, Castaing D, Azoulay D. Long-term outcomes after hepatic resection for colorectal metastases in young patients. Cancer. 2009;116(3):647–58.CrossRef
7.
Kemeny N. The management of resectable and unresectable liver metastases from colorectal cancer. Curr Opin Oncol. 2010;22(4):364–73.CrossRefPubMed
8.
Folprecht G, Grothey A, Alberts S, Raab HR, Köhne CH. Neoadjuvant treatment of unresectable colorectal liver metastases: correlation between tumour response and resection rates. Ann Oncol. 2005;16(8):1311–9.CrossRefPubMed
9.
Gruenberger T, Bridgewater J, Chau I, García Alfonso P, Rivoire M, Mudan S, Lasserre S, Hermann F, Waterkamp D, Adam R. Bevacizumab plus mFOLFOX-6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: the OLIVIA multinational randomised phase II trial. Ann Oncol. 2015;26(4):702–8.CrossRefPubMed
10.
Ye L-C, Liu T-S, Ren L, Wei Y, Zhu D-X, Zai S-Y, Ye Q-H, Yu Y, Xu B, Qin X-Y, et al. Randomized Controlled Trial of Cetuximab Plus Chemotherapy for Patients With <i>KRAS</i> Wild-Type Unresectable Colorectal Liver-Limited Metastases. J Clin Oncol. 2013;31(16):1931–8.CrossRefPubMed
11.
Masi G, Loupakis F, Pollina L, Vasile E, Cupini S, Ricci S, Brunetti IM, Ferraldeschi R, Naso G, Filipponi F, et al. Long-term outcome of initially unresectable metastatic colorectal cancer patients treated with 5-fluorouracil/leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) followed by radical surgery of metastases. Ann Surg. 2009;249(3):420–5.CrossRefPubMed
12.
13.
Chang AE, Schneider PD, Sugarbaker PH, Simpson C, Culnane M, Steinberg SM. A prospective randomized trial of regional versus systemic continuous 5-fluorodeoxyuridine chemotherapy in the treatment of colorectal liver metastases. Ann Surg. 1987;206(6):685–93.CrossRefPubMedPubMedCentral
14.
Hohn DC, Stagg RJ, Friedman MA, Hannigan JF Jr, Rayner A, Ignoffo RJ, Acord P, Lewis BJ. A randomized trial of continuous intravenous versus hepatic intraarterial floxuridine in patients with colorectal cancer metastatic to the liver: the Northern California Oncology Group trial. J Clin Oncol. 1989;7(11):1646–54.CrossRefPubMed
15.
Fiorentini G, Rossi S, Dentico P, Meucci F, Bonechi F, Bernardeschi P, Cantore M, Guadagni S, De Simone M. Oxaliplatin hepatic arterial infusion chemotherapy for hepatic metastases from colorectal cancer: a phase I-II clinical study. Anticancer Res. 2004;24(3b):2093–6.PubMed
16.
Boilève A, De Cuyper A, Larive A, Mahjoubi L, Najdawi M, Tazdait M, Gelli M, Tselikas L, Smolenschi C, Malka D, et al. Hepatic arterial infusion of oxaliplatin plus systemic chemotherapy and targeted therapy for unresectable colorectal liver metastases. Eur J Cancer. 2020;138:89–98.CrossRefPubMed
17.
Kemeny NE, Jarnagin WR, Capanu M, Fong Y, Gewirtz AN, Dematteo RP, D’Angelica MI. Randomized Phase II Trial of Adjuvant Hepatic Arterial Infusion and Systemic Chemotherapy With or Without Bevacizumab in Patients With Resected Hepatic Metastases From Colorectal Cancer. J Clin Oncol. 2011;29(7):884–9.CrossRefPubMed
18.
Dzodic R, Gomez-Abuin G, Rougier P, Bonnay M, Ardouin P, Gouyette A, Rixe O, Ducreux M, Munck JN. Pharmacokinetic advantage of intra-arterial hepatic oxaliplatin administration: comparative results with cisplatin using a rabbit VX2 tumor model. Anticancer Drugs. 2004;15(6):647–50.CrossRefPubMed
19.
Ducreux M, Ychou M, Laplanche A, Gamelin E, Lasser P, Husseini F, Quenet F, Viret F, Jacob J-H, Boige V, et al. Hepatic Arterial Oxaliplatin Infusion Plus Intravenous Chemotherapy in Colorectal Cancer With Inoperable Hepatic Metastases: A Trial of the Gastrointestinal Group of the Fédération Nationale des Centres de Lutte Contre le Cancer. J Clin Oncol. 2005;23(22):4881–7.CrossRefPubMed
20.
Boige V, Malka D, Elias D, Castaing M, De Baere T, Goere D, Dromain C, Pocard M, Ducreux M. Hepatic Arterial Infusion of Oxaliplatin and Intravenous LV5FU2 in Unresectable Liver Metastases from Colorectal Cancer after Systemic Chemotherapy Failure. Ann Surg Oncol. 2008;15(1):219–26.CrossRefPubMed
21.
Lim A, Le Sourd S, Senellart H, Luet D, Douane F, Perret C, Bouvier A, Métairie S, Cauchin E, Rougier P, et al. Hepatic Arterial Infusion Chemotherapy for Unresectable Liver Metastases of Colorectal Cancer: A Multicenter Retrospective Study. Clin Colorectal Cancer. 2017;16(4):308–15.CrossRefPubMed
22.
Lewis HL, Bloomston M. Hepatic Artery Infusional Chemotherapy. Surg Clin North Am. 2016;96(2):341–55.CrossRefPubMed
23.
Cercek A, Boucher TM, Gluskin JS, Aguiló A, Chou JF, Connell LC, Capanu M, Reidy-Lagunes D, D’Angelica M, Kemeny NE. Response rates of hepatic arterial infusion pump therapy in patients with metastatic colorectal cancer liver metastases refractory to all standard chemotherapies. J Surg Oncol. 2016;114(6):655–63.CrossRefPubMedPubMedCentral
24.
Tsimberidou AM, Leick MB, Lim J, Fu S, Wheler J, Piha-Paul SA, Hong D, Falchook GS, Naing A, Subbiah IM, et al. Dose-finding study of hepatic arterial infusion of oxaliplatin-based treatment in patients with advanced solid tumors metastatic to the liver. Cancer Chemother Pharmacol. 2013;71(2):389–97.CrossRefPubMed
25.
Boilève A, Maillard A, Wagner M, Dromain C, Laurent C, Dupont Bierre E, Le Sourd S, Audemar F, Ulusakarya A, Guerin-Meyer V, et al. Treatment intensification with hepatic arterial infusion chemotherapy in patients with liver-only colorectal metastases still unresectable after systemic induction chemotherapy - a randomized phase II study – SULTAN UCGI 30/PRODIGE 53 (NCT03164655)- study protocol. BMC Cancer. 2020;20(1):74.CrossRefPubMedPubMedCentral
26.
Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. US Department of Health and Human Services, National Institutes of Health, National Cancer Institute; 2010.
Metadata
Title
Hepatic arterial infusion in combination with systemic chemotherapy in patients with hepatic metastasis from colorectal cancer: a randomized phase II study – (NCT05103020) – study protocol
Authors
Ji Su Kim
Hyunwook Kim
Seo Young Lee
Yoon Dae Han
Kichang Han
Byung Soh Min
Man-Deuk Kim
Jong Yun Won
Seung-Hoon Beom
Sang Joon Shin
Han Sang Kim
Dai Hoon Han
Joong Bae Ahn
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11085-w

Other articles of this Issue 1/2023

BMC Cancer 1/2023 Go to the issue

Research

Urinary tract infection after radiation therapy or radical prostatectomy on the prognosis of patients with prostate cancer: a population-based study

Research

Socio-demographic and health-related determinants of patients’ overall rating and experiences of cancer care

Research

A body shape index (ABSI) is associated inversely with post-menopausal progesterone-receptor-negative breast cancer risk in a large European cohort

Research

Cytokine release syndrome was an independent risk factor associated with hypoalbuminemia for patients with relapsed/refractory hematological malignancies after CAR-T cell therapy

Research

A nomogram based on platelet-to-lymphocyte ratio for predicting pathological complete response of breast cancer after neoadjuvant chemotherapy

Research

Genome editing approaches with CRISPR/Cas9: the association of NOX4 expression in breast cancer patients and effectiveness evaluation of different strategies of CRISPR/Cas9 to knockout Nox4 in cancer cells
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits