PRODIGE 53-UCGI 30 (SULTAN): A randomized phase II study comparing treatment intensification with hepatic arterial infusion chemotherapy plus systemic chemotherapy to systemic chemotherapy alone in patients with liver-only colorectal metastases considered still non resectable after at least two months of systemic induction chemotherapy.

Abstract

TPS3619 Background: In the first-line setting, current combination chemotherapy (CT) achieve high objective response rates (ORR) ranging from 40% to 80% and leads to complete resection rate (CRR) of colorectal cancer liver metastasis (CRCLM) in 25% to 50% of patients with initially non-resectable CRLM. However, when patients with CRLM are still not amenable to resection after induction CT, ORRs (~5-30%) and CRRs ( < 10%) obtained with second-line systemic CT are much lower. Combining hepatic arterial infusion (HAI) and systemic (SYS) CT for unresectable CRLM lead to high ORR and the potential of cure in the second-line and further setting. Methods: This multicenter randomized phase II trial conducted in 20 centers in France plans to include 140 patients with CRLM still not amenable to a curative intent-treatment after at least two months of first-line induction SYS CT whatever the tumor response. Patients are randomized (1:1) between intensified biweekly regimen combining HAI oxaliplatin (100 mg/m²) and SYS FOLFIRI (leucovorin 400 mg/m², irinotecan 180 mg/m², and 5-FU 2.4 g/m²over 48 h) plus cetuximab 500 mg/m² or bevacizumab 5 mg/kg (according to RAS status and prior response/tolerance to SYS induction CT) or SYS CT alone according to current guidelines. The primary endpoint is to evaluate and compare the curative-intent (R0-R1) resection (and/or ablation) rate (CRR) of CRLM in both arms. A gain of 20% in CRR is expected (30% in the experimental arm vs. 10% in the control arm; α 5% [two-sided]; β 20%). Stratification factors at randomization are prior adjuvant or SYS induction oxaliplatin-based CT, tumor response to SYS induction CT, and center. Secondary endpoints include progression-free (overall, hepatic and extrahepatic) and overall survival, ORR, relative change in the sum of longest diameters of RECIST target lesions (DoR) and feasibility/tolerability. Since study start, 3 patients have been enrolled to date (planned accrual period: 3 years). Clinical trial information: NCT03164655.