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

Alice Boilève, Aline Maillard, Mathilde Wagner, Clarisse Dromain, Christophe Laurent, Eric Dupont Bierre, Samuel Le Sourd, Franck Audemar, Ayhan Ulusakarya, Veronique Guerin-Meyer, Denis Smisth, Veronica Pezzella, Thierry De Baere, Diane Goere, Maximiliano Gelli, Julien Taieb, Valérie Boige, Alice Boilève, Aline Maillard, Mathilde Wagner, Clarisse Dromain, Christophe Laurent, Eric Dupont Bierre, Samuel Le Sourd, Franck Audemar, Ayhan Ulusakarya, Veronique Guerin-Meyer, Denis Smisth, Veronica Pezzella, Thierry De Baere, Diane Goere, Maximiliano Gelli, Julien Taieb, Valérie Boige

Abstract

Background: Approximately 40% of colorectal cancer patients will develop colorectal liver metastases (CRLM). The most effective approach to increase long-term survival is CRLM complete resection. Unfortunately, only 10-15% of CRLM are initially considered resectable. The objective response rates (ORR) after current first-line systemic chemotherapy (sys-CT) regimens range from 40 to 80% and complete resection rates (CRR) range from 25 to 50% in patients with initially unresectable CRLM. When CRLM patients are not amenable to complete resection after induction of sys-CT, ORRs obtained with second-line sys-CT are much lower (between 10 and 30%) and consequently CRRs are also low (< 10%). Hepatic arterial infusion (HAI) oxaliplatin may represent a salvage therapy in patients with CRLM unresectable after one or more sys-CT regimens with ORRs and CRRs up to 60 and 30%, respectively. This study is designed to evaluate the efficacy of an intensification strategy based on HAI oxaliplatin combined with sys-CT as a salvage treatment in patients with CRLM unresectable after at least 2 months of first-line induction sys-CT.

Objectives and endpoints of the phase ii study: Our main objective is to investigate the efficacy, in term of CRR (R0-R1), of treatment intensification in patients with liver-only CRLM not amenable to curative-intent resection (and/or ablation) after at least 2 months of induction sys-CT. Patients will receive either HAI oxaliplatin plus systemic FOLFIRI plus targeted therapy (i.e. anti-EGFR antibody or bevacizumab) or conventional sys-CT plus targeted therapy (i.e. anti-EGFR or antiangiogenic antibody). Secondary objectives are to compare: progression-free survival, overall survival, objective response rate, depth of response, feasibility of delivering HAI oxaliplatin including HAI catheter-related complications, and toxicity (NCI-CTCAE v4.0).

Methods: This study is a multicenter, randomized, comparative phase II trial (power, 80%; two-sided alpha-risk, 5%). Patients will be randomly assigned in a 1:1 ratio to receive HAI oxaliplatin combined with systemic FOLFIRI plus targeted therapy (experimental arm) or the best sys-CT plus targeted therapy on the basis of their first-line prior sys-CT history and current guidelines (control arm). One hundred forty patients are required to account for non-evaluable patients.

Trial registration: ClinicalTrials.gov, (NCT03164655). Trial registration date: 11th May 2017.

Keywords: Colorectal cancer; Hepatic arterial infusion; Liver metastases; Liver resection; Oxaliplatin; Randomized trial.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram of the SULTAN study. L1: line 1; HAI: hepatic arterial infusion; CRLM: colorectal liver metastases; MRI: Magnetic resonance imaging; CT-TAP: computed tomography of thorax, abdomen and pelvis; QLQ: quality of life questionnaire

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