ARCHER trial opens enrollment to assess shorter duration of radiation therapy for MIBC

Enrollment in now open in the phase 3 ARCHER trial (NRG-GU015; NCT07097142), which is assessing the safety and efficacy of a shorter duration of radiation therapy in patients with muscle invasive bladder cancer (MIBC), NRG Oncology announced in a news release.¹

“A quarter of all bladder cancers in the United States are muscle-invasive bladder cancers,” said principal investigator Scott Delacroix, MD, of the Mary Bird Perkins Cancer Center in the news release.¹ “Currently, the standard of care treatment for this disease consists of either (1) bladder preservation with transurethral resection of bladder tumor (TURBT), chemotherapy, and radiation; or (2) neoadjuvant chemotherapy and surgical removal of the bladder (cystectomy). These 2 pathways of treatment have comparable survival rates, and both are considered standard of care in this disease. Although very different from patient’s perspective, both treatment options require frequent visits to specialized centers over several months. 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.”

To that end, the ARCHER trial is seeking to enroll 486 adult patients with MIBC to determine whether ultra-hypofractionated delivery of stereotactic body radiation therapy (SBRT) is non-inferior to hypofractionated radiotherapy in terms of bladder-intact event-free survival (EFS) at 3 years.

To be eligible for enrollment, patients must have a Zubrod performance status of 2 or less and must undergo a TURBT prior to study start. Additionally, patients must have an absolute neutrophil count of at least 1500 cells/mm³ and creatinine clearance of at least 30 mL/min.

Patients enrolled in the study will be randomly assigned to receive either 4 weeks of daily hypofractionated radiotherapy (55 Gy in 20 fractions) or 5 days of ultra-hypofractionated SBRT (32.5 Gy in 5 fractions) over 4 weeks. All patients also receive standard of care chemotherapy, with cisplatin, gemcitabine, or mitomycin and 5-fluorouracil.

In addition to the primary end point of bladder-intact EFS, secondary end points include the incidence of urinary adverse events (AEs), incidence of bowel AEs, quality of life measures, EFS, metastasis-free survival, overall survival, and the overall incidence of AEs.

“The translational components built into this trial will help guide the future care of our patients and next generation of trials,” added Catherine Spina, MD, PhD, of Columbia University and co-Chair for Translational Science for NRG-GU015, in the news release.¹ “The study team will collect and utilize integrated biomarker circulating tumor DNA (ctDNA) data as a predefined secondary end point to define further the role of ctDNA for predicting disease recurrence in the context of muscle invasive bladder cancer.”

The investigators also plan to assess the prognostic utility of urine tumor deoxyribonucleic acid.

Final completion of the trial is expected in May 2030.

Co-principal investigator Himanshu Nagar, MD, MS, of Memorial Sloan Kettering Cancer Center, concluded in the news release,¹ “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.”

REFERENCES

1. NRG Oncology opens new “ARCHER” clinical trial (NRG-GU015) testing a shorter treatment duration of radiation therapy for muscle invasive bladder cancer. News release. NRG Oncology. August 14, 2025. Accessed August 14, 2025. https://www.eurekalert.org/news-releases/1094653

2. Testing shorter duration radiation therapy versus the usual radiation therapy in patients receiving the usual chemotherapy treatment for bladder cancer, ARCHER study. ClinicalTrials.gov. Last updated July 31, 2025. Accessed August 14, 2025. https://clinicaltrials.gov/study/NCT07097142