A multicenter phase II study of modified FOLFIRINOX for first-line treatment for advanced urachal cancer (ULTMA; KCSG GU20–03)

Background: Systemic therapy is used for advanced urachal cancer that is not amenable to surgery. However, due to the low incidence of this disease, prospective clinical trials have not been conducted and there is no established standard of care. 5-FU, oxaliplatin, and irinotecan have synergistic mechanisms of action, do not overlap in major side effects, and all have the potential to be effective in urachal cancer. The ongoing ULTIMA trial (NCT04611724) is evaluating the efficacy and safety of modified FOLFIRINOX in patients with advanced urachal cancer. Methods: Patients with recurrent or metastatic urachal cancer with measurable lesions 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) with prophylactic pegteograstim 6 mg SC on day 3 Q2W till 12 cycles (or until progression or unacceptable toxicities). Response evaluation was done every 6 weeks. The primary endpoint is an ORR. The secondary objectives include PFS, OS and incidence of febrile neutropenia. Simon’s minimax two-stage design was employed to test null hypothesis P0=17% and P1=36%, with alpha of 5% and beta of 20%. The primary endpoint was met at the first stage and we decided to report the results. Results: From April 2021 to November 2023, 21 patients with advanced urachal cancer were enrolled in 5 cancer centers. A median age was 50 (28–68) and 15 were male. Lung was the most frequent site of metastasis (47.6%) followed by lymph node (38.1%) and peritoneal seeding (33.3%). As of December 2023, 18 patients discontinued treatment. A total of 235 cycles were administered with a median of 12 (6–12) cycles per patient. Two patients achieved CR and 11 patients PR with an ORR of 61.9%; the study met the primary endpoint in the first stage. With a median FU duration of 15.2 months, the median PFS was 9.3 months (95% CI, 6.6~12.0) and estimated median OS was 26.4 months (95% CI, 14.7–38.1). The treatment was tolerable and have no unexpected adverse events. Grade 3 adverse events included neutropenia (4.8%), anemia (9.5%), thrombocytopenia (4.8%) and diarrhea (4.8%). There were neither febrile neutropenia nor grade 4 adverse events. Conclusions: The first prospective ULTIMA study showed encouraging ORR and PFS in patients with advanced urachal cancer. The regimen is well tolerated without febrile neutropenia with prophylactic pegteograstim. Further analysis of efficacy will be presented. Clinical trial information: NCT04611724. Research Sponsor: None.