Testing Shorter Duration Radiation Therapy Versus the Usual Radiation Therapy in Patients Receiving the Usual Chemotherapy Treatment for Bladder Cancer, ARCHER Study

NCT ID: NCT07097142

Last Updated: 2025-07-31

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 486 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-14
• Study Completion Date: 2030-05-31

Brief Summary

This phase III trial compares the effect of shorter term radiation (ultra-hypofractionated) therapy to the usual radiation therapy (hypofractionation) with standard of care chemotherapy, with cisplatin, gemcitabine or mitomycin and 5-fluorouracil for the treatment of patients with muscle invasive bladder cancer. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Ultra-hypofractionated radiation therapy delivers radiation over an even shorter period of time than hypofractionated radiation therapy. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill tumor cells. Chemotherapy drugs, such as mitomycin-C and 5-fluorouracil (5-FU), work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ultra-hypofractionated radiation may be equally effective as hypofractionated therapy for patients with muscle invasive bladder cancer.

Detailed Description

Demonstrate non-inferiority of ultra-hypofractionated (stereotactic body radiation therapy [SBRT]) compared to hypofractionated radiation therapy (RT) with a 10% non-inferiority margin (from 50% to 40%) in the rate of bladder-intact event-free survival (BI-EFS) at 3 years (corresponding to a hazard ratio < 1.32).

Conditions

Bladder Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I (hypofractionated radiation therapy)

Patients receive hypofractionated RT QD, Monday to Friday, for 20 treatments in the absence of disease progression or unacceptable toxicity. Patients also receive one of 3 systemic chemotherapy regimens per treating physician's choice: 1) cisplatin IV weekly for 4 weeks; 2) gemcitabine IV on days 1, 4, 8, 11, 15, 18, 22 and 25 or weekly for 4 weeks; or 3) mitomycin-C IV on day 1 and 5 FU, over 120 hours on days 1-5 and 22-26. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan and/or MRI or FDG PET throughout the study. In addition, patients may undergo optional blood and urine sample collection throughout the study, as well as an optional biopsy during cystoscopy during follow up.

Group Type: ACTIVE_COMPARATOR

Hypofractionated Radiation Therapy

Intervention Type: RADIATION

Undergo hypofractionated radiation therapy

Cisplatin

Intervention Type: DRUG

Given IV

Gemcitabine

Intervention Type: DRUG

Given IV

Mitomycin

Intervention Type: DRUG

Given IV

Fluorouracil

Intervention Type: DRUG

Given IV

Computed Tomography

Intervention Type: PROCEDURE

Undergo CT scan

Magnetic Resonance Imaging

Intervention Type: PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type: PROCEDURE

Undergo PET scan

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood, tissue, and urine sample collection

Arm II (Ultrahypofractionated radiation therapy)

Patients receive ultra-hypofractionated RT QD, no more than twice weekly, for 5 treatments in the absence of disease progression or unacceptable toxicity. Patients also receive one of 3 systemic chemotherapy regimens per treating physician's choice: 1) cisplatin IV weekly for 4 weeks; 2) gemcitabine IV on days 1, 4, 8, 11, 15, 18, 22 and 25 or weekly for 4 weeks; or 3) mitomycin-C IV on day 1 and 5 FU, over 120 hours on days 1-5 and 22-26. Treatment given in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan and/or MRI or FDG PET throughout the study. In addition, patients may undergo optional blood and urine sample collection throughout the study, as well as an optional biopsy during cystoscopy during follow up.

Group Type: EXPERIMENTAL

Hypofractionated Radiation Therapy

Intervention Type: RADIATION

Undergo hypofractionated radiation therapy

Cisplatin

Intervention Type: DRUG

Given IV

Gemcitabine

Intervention Type: DRUG

Given IV

Mitomycin

Intervention Type: DRUG

Given IV

Fluorouracil

Intervention Type: DRUG

Given IV

Computed Tomography

Intervention Type: PROCEDURE

Undergo CT scan

Magnetic Resonance Imaging

Intervention Type: PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type: PROCEDURE

Undergo PET scan

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood, tissue, and urine sample collection

Survey Administration

Intervention Type: OTHER

Ancillary studies

Interventions

Hypofractionated Radiation Therapy

Undergo hypofractionated radiation therapy

Intervention Type: RADIATION

Cisplatin

Given IV

Intervention Type: DRUG

Gemcitabine

Given IV

Intervention Type: DRUG

Mitomycin

Given IV

Intervention Type: DRUG

Fluorouracil

Given IV

Intervention Type: DRUG

Computed Tomography

Undergo CT scan

Intervention Type: PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

Intervention Type: PROCEDURE

Positron Emission Tomography

Undergo PET scan

Intervention Type: PROCEDURE

Biospecimen Collection

Undergo blood, tissue, and urine sample collection

Intervention Type: PROCEDURE

Survey Administration

Ancillary studies

Intervention Type: OTHER

Other Intervention Names

Hypofractionated, hypofractionated radiation therapy, Hypofractionated Radiotherapy, Hypofractionated Radiotherapy, hypofractionation, Radiation, Hypofractionated; (SP-4-2)-Diamminedichloroplatinum, 15663-27-1, Abiplatin, Blastolem, Briplatin, CDDP; 1-(2-Oxo-4-amino-1,2-dihydropyrimidin-1-yl)-2-deoxy-2,2-difluororibose, 2'Deoxy-2',2'-Difluorocytidine, 95058-81-4, dFdC, dFdCyd, Difluorodeoxycytidine; (1aS,8S,8aR,8bS)-6-Amino-8-[[(aminocarbonyl)oxy]methyl]-1; 2,4-Dioxo-5-fluoropyrimidine, 5 Fluorouracil, 5 Fluorouracilum, 5 FU; CAT, CAT Scan, CAT scan, CAT Scan, Computed Axial Tomography, Computed Tomography; Magnetic Resonance, Magnetic Resonance Imaging, Magnetic Resonance Imaging; Medical Imaging, Positron Emission Tomography, PET, PET, Pet Scan; Biological Sample Collection, Biological Sample Collection, Biospecimen Collected, Biospecimen Collection, Specimen Collection

Eligibility Criteria

Inclusion Criteria

• Histologically proven, cT2-T3,N0M0 urothelial carcinoma of the bladder prior to randomization.

• Note: Patients with mixed urothelial carcinoma will be eligible for the trial, but the presence of small cell carcinoma will make a patient ineligible
• Must undergo a transurethral resection of bladder tumor (TURBT) prior to randomization. Patients may have either completely or partially resected tumors as long as the treating urologist attempted maximal resection
• Must undergo radiological staging prior to randomization. Imaging of chest, abdomen, and pelvis must be performed using CT or MRI (with or without contrast is acceptable). Patients must not have evidence of T4 or node positive disease. Fludeoxyglucose (FDG) PET Imaging is acceptable for radiological staging
• If any lymph nodes ≥ 1.0 cm in shortest cross-sectional diameter are noted on imaging (CT / MRI of abdomen and pelvis), then the patient must have had a biopsy of the enlarged lymph node showing no tumor involvement prior to randomization
• No diffuse carcinoma in situ (CIS) based on cystoscopy and biopsy
• No definitive clinical or radiologic evidence of metastatic disease
• Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder within 24 months prior to registration except Ta/T1/Carcinoma in situ (CIS) of the upper urinary tract including renal pelvis and ureter if the patient had undergone complete nephroureterectomy
• Age ≥ 18
• Zubrod performance status of ≤ 2
• Not pregnant and not nursing

• Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm^3
• Platelets ≥ 100,000 cells/mm^3
• Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb]) ≥ 8.0 g/dl is acceptable)
• Creatinine clearance (CrCL) of ≥ 30 mL/min by the Cockcroft-Gault formula
• Total bilirubin ≤ 2 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3 x institutional ULN
• All adverse events associated with any prior therapy must have resolved to Common Terminology Criteria for Adverse Events (CTCAE) grade ≤ 3 prior to randomization
• For patients who have completed neoadjuvant therapy, they are eligible if the pre-neoadjuvant therapy diagnosis (TURBT path) is within 180 days before randomization
• Must not have had prior pelvic radiation
• New York Heart Association Functional Classification II or better (NYHA Functional Classification III/IV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)
• No active infection requiring IV antibiotics
• Patients with hydronephrosis are eligible if they have unilateral hydronephrosis and kidney function meet criteria specified

Exclusion Criteria

-

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NRG Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

NRG-GU015

Identifier Type: -

Identifier Source: org_study_id