The phase 3 ARCHER trial (NRG-GU015; NCT07097142) has opened enrollment to evaluate whether a dramatically shortened radiation therapy regimen can match the effectiveness of standard treatment for muscle invasive bladder cancer (MIBC) while significantly reducing patient burden. The study, announced by NRG Oncology, seeks to enroll 486 adult patients to compare ultra-hypofractionated stereotactic body radiation therapy (SBRT) delivered over just 5 days versus the current standard of 20 radiation treatments over 4 weeks.
Addressing Critical Treatment Barriers
Muscle invasive bladder cancer represents approximately 25% of all bladder cancer cases in the United States, according to principal investigator Scott Delacroix, MD, of the Mary Bird Perkins Cancer Center. Current standard of care involves two treatment pathways with comparable survival rates: bladder preservation through transurethral resection of bladder tumor (TURBT), chemotherapy, and radiation; or neoadjuvant chemotherapy followed by surgical bladder removal (cystectomy).
"Both treatment options require frequent visits to specialized centers over several months," Delacroix explained. "Up to 20% of the patients with muscle invasive bladder cancer do not receive one of these curative intent treatments because of logistical concerns. Reducing the burden of frequent travel to the radiation center is highly attractive to patients and their families."
Trial Design and Treatment Arms
The randomized study will assign patients to receive either the established regimen of 55 Gray (Gy) administered in 20 fractions over 4 weeks, or the experimental ultra-hypofractionated course of 32.5 Gy delivered in 5 fractions over 4 weeks. All participants will also receive standard chemotherapy with cisplatin, gemcitabine, or mitomycin and 5-fluorouracil.
To be eligible, patients must have a Zubrod performance status of 2 or less, undergo TURBT prior to study start, maintain an absolute neutrophil count of at least 1,500 cells/mm³, and have creatinine clearance of at least 30 mL/min.
Primary and Secondary Endpoints
The primary endpoint focuses on bladder-intact event-free survival (EFS) at 3 years, testing whether the ultra-hypofractionated SBRT approach is non-inferior to standard hypofractionated radiotherapy. Secondary endpoints include incidence of urinary and bowel adverse events, quality of life measures, EFS, metastasis-free survival, overall survival, and overall incidence of adverse events.
Translational Research Components
The trial incorporates significant translational research elements aimed at advancing personalized medicine approaches. "The translational components built into this trial will help guide the future care of our patients and next generation of trials," said Catherine Spina, MD, PhD, of Columbia University and co-Chair for Translational Science for NRG-GU015.
The study team will collect and analyze circulating tumor DNA (ctDNA) data as a predefined secondary endpoint to better define the role of ctDNA in predicting disease recurrence in muscle invasive bladder cancer. Investigators also plan to assess the prognostic utility of urine tumor DNA, potentially providing non-invasive biomarkers for future treatment decisions.
Potential Impact on Patient Care
Co-principal investigator Himanshu Nagar, MD, MS, of Memorial Sloan Kettering Cancer Center, emphasized the potential benefits: "If we can safely reduce the number of treatments without sacrificing bladder preservation rate, we can meaningfully reduce patient burden—fewer visits, lower cumulative toxicity, and less financial and psychosocial stress—and ultimately improve quality of life."
The ultra-hypofractionated approach leverages advances in radiation physics and imaging to precisely target tumors while sparing adjacent healthy tissues, potentially reducing both treatment duration and cumulative toxicity.
Study Timeline and Collaboration
Final completion of the ARCHER trial is expected in May 2030. The study represents a collaborative effort involving distinguished investigators from premier cancer centers, including Mary Bird Perkins Cancer Center, Memorial Sloan Kettering Cancer Center, and Columbia University, reflecting NRG Oncology's multidisciplinary approach to practice-changing clinical research.
The trial is accessible on ClinicalTrials.gov under identifier NCT07097142, with detailed protocol documents available via CTSU.org across NRG Oncology's network of over 1,300 research sites in North America and beyond.
