A multicenter phase II study of first-line modified FOLFIRINOX in patients with advanced urachal cancer (ULTIMA; KCSG GU20-03).

758 Background: There is no established standard treatment for recurrent or metastatic urachal cancer (UrC). Combination regimens containing 5-fluorouracil (5-FU), oxaliplatin, and irinotecan have demonstrated promising efficacy and manageable toxicity in various gastrointestinal malignancies and may also be effective in UrC. We conducted a multicenter phase II study to evaluate the efficacy and safety of modified FOLFIRINOX in patients with advanced UrC. Methods: Patients with recurrent or metastatic UrC and measurable disease received modified FOLFIRINOX (oxaliplatin 85 mg/m² over 2 hours, irinotecan 150 mg/m² over 1.5 hours, leucovorin 400 mg/m² over 2 hours, and 5-FU 2400 mg/m² over 46 hours) together with prophylactic pegteograstim 6 mg subcutaneously on day 3 of each 2-week cycle, up to 12 cycles (or until disease progression or unacceptable toxicity). Tumor response was assessed every 6 weeks. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and incidence of febrile neutropenia. Simon’s minimax two-stage design was used to test the null hypothesis of P₀ = 17% versus the alternative P₁ = 36%, with α = 0.05 and β = 0.20. Results: Between April 2021 and April 2025, 35 patients with advanced UrC were enrolled across six centers. The median age was 51 years (range, 28–68), and 24 patients (68.6%) were male. The most common metastatic sites were lung (48.6%), peritoneum (37.1%), and lymph nodes (31.4%). As of October 2025, 33 patients had discontinued treatment; 27 completed all 12 planned cycles. A total of 464 cycles were administered, with a median of 12 (range, 6–43) cycles per patient. The ORR was 57.1% (2 complete and 18 partial responses), and the disease control rate was 100%. After a median follow-up of 26.4 months, the median PFS was 9.5 months (95% CI, 8.7–10.2), and the estimated median OS was 25.5 months (95% CI, 16.5–34.6). Treatment was well tolerated with no unexpected toxicities. The most common any-grade adverse events (AEs) were peripheral neuropathy (74.3%), nausea (65.7%), thrombocytopenia (37.1%), fatigue (28.6%), anorexia (20.0%), and mucositis (20.0%). Grade 3 AEs included thrombocytopenia (8.6%), neutropenia (5.7%), anemia (5.7%), nausea (2.9%), and diarrhea (2.9%). No febrile neutropenia or grade 4 AEs were observed. Conclusions: The ULTIMA trial is the first prospective phase II study in advanced urachal cancer and met its primary endpoint, demonstrating encouraging ORR and PFS. Modified FOLFIRINOX was well tolerated, with no febrile neutropenia under prophylactic pegteograstim support. This regimen may be considered a potential standard treatment option for patients with advanced urachal cancer. Clinical trial information: NCT04611724 .