Daily Online Adaptive Short-Course Radiation Therapy and Concurrent Chemotherapy for Muscle-Invasive Bladder Cancer

NCT05700227 | Terminated FDA Device

• 1 other identifier: VAR-2021-05
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is a single-arm, prospective, multi-center clinical trial designed to demonstrate that adaptive radiotherapy for muscle-invasive bladder cancer will translate into a decreased rate of acute (assessed weekly during chemo-radiotherapy) grade 3 or greater gastrointestinal/genitourinary toxicity compared with the historically reported rate for non-adaptive radiation therapy. The Common Terminology Criteria for Adverse Events (CTCAE) version 5 assessment tool will be utilized.

Conditions

Muscle Invasive Bladder Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Acute GI/GU Toxicity

  Acute gastrointestinal and genitourinary CTCAE v5 grade 3 or higher toxicity

  Assessed during the 4 weeks of external beam radiation therapy

Secondary Outcomes (13)

• Loco-regional Tumor Control

  From baseline to 24 months after completion of chemoradiotherapy

• Patient-reported Quality of Life

  From baseline to 24 months after completion of chemoradiotherapy

• Adverse Events

  From the start of external beam radiation therapy to 24 months after completion chemoradiotherapy

• Global Function

  From baseline to 24 months after completion of chemoradiotherapy

• Disease-free Survival

  From the start of external beam radiation therapy to 24 months after completion chemoradiotherapy

Other Outcomes (1)

• Exploratory Translational Objective

  From the start of external beam radiation therapy to 24 months after completion chemoradiotherapy

Study Arms (1)

Daily Adaptive External Beam Radiation Therapy

EXPERIMENTAL

Daily adaptive radiation therapy delivered with Varian Ethos treatment system

Radiation: Daily Adaptive External Beam Radiation Therapy

Interventions

Daily Adaptive External Beam Radiation Therapy RADIATION

Daily adaptive external beam radiation therapy delivered on Varian Ethos treatment system.

Daily Adaptive External Beam Radiation Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Patients must have histologically proven cT2-T4aN0M0 (AJCC v8) urothelial carcinoma of the bladder with an intact bladder. Mixed urothelial histology is permitted as long as there is some urothelial histology component and no small cell component present.
• Patients must have undergone an attempt at maximal transurethral resection of bladder tumor (TURBT) within 70 days prior to enrollment.
• A negative pelvic nodal status is to be confirmed by one or more of the following studies/procedures: PET/CT scan, CT scan, MRI scan, fine needle biopsy, extra peritoneal biopsy, or laparoscopic biopsy, per institutional standard of care.
• Patients must be planning to undergo concurrent pelvic radiation and chemotherapy with curative intent.
• ECOG performance status ≤2 (Karnofsky ≥60%).
• Ability to complete required patient questionnaires.
• Ability to understand and the willingness to sign a written informed consent document.
• Patients must have normal organ and marrow function as defined below, obtained within 28 days prior to enrollment:
• absolute neutrophil count ≥1,500/mcL
• platelets ≥100,000/mcL
• hemoglobin ≥9 g/dL (can be transfused with red blood cells pre-study)
• total bilirubin ≤1.5 × institutional upper limit of normal (ULN) unless the patient has Gilbert's syndrome who must have total bilirubin \<3.0 mg/dL
• AST(SGOT)/ALT(SGPT) ≤3 × ULN
• alkaline phosphatase ≤2.5 × ULN

You may not qualify if:

• Grade ≥ 2 CTCAE GI or grade ≥ 3 GU symptoms/conditions at baseline (including ongoing refractory gross hematuria post TURBT)
• Patients with clinically involved nodes (nodes consistent morphologically with malignancy and which are greater than 1 cm on short axis on CT or MRI).
• Patients with cT4b disease. Patients with T4 disease after 8 subjects with T4 disease have been enrolled.
• Bilateral hydronephrosis or diffuse carcinoma in situ based on cystoscopy or biopsy. Unilateral hydronephrosis is allowed provided the patient's kidney function meets the trial criteria. Patients should be evaluated for consideration of stenting or nephrostomy tubes for moderate-to-severe unilateral hydronephrosis prior to initiation of chemo-radiotherapy.
• Prior radiation therapy to the pelvis or abdominal cavity, prior systemic chemotherapy/systemic therapy for bladder cancer. Prior intravesical therapy (BCG, interferon, intravesical chemotherapy) is allowed provided the time interval from completion of intravesical therapy is at least 3 months.
• Prior cystectomy or partial cystectomy.
• Prior malignancy (except for non-melanoma skin cancer) unless disease-free for at least 2 years. Prior non-muscle invasive bladder cancer is allowed. Patients must not have a history of urothelial carcinoma or variant histology at any site outside of the urinary bladder within the previous 24 months except Ta/T1/carcinoma in situ of the upper urinary tract (including renal pelvis and ureter) provided the patient has undergone complete nephroureterectomy and still meets trial eligibility for creatinine clearance. Patients with localized prostate cancer who are being followed on an active surveillance program are also eligible.
• Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
• Prior systemic anticancer therapy due to a diagnosis of cancer (e.g., chemotherapy, targeted therapy, immunotherapy) within 3 years prior to entering the study or induction chemotherapy prior to the start of concurrent chemo-radiotherapy
• Serious medical comorbidities precluding RT and/or chemotherapy (e.g., active uncontrolled infection )
• Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease.
• Patients with scleroderma. Patients who are symptomatic from other auto-immune diseases or patients on biologic therapies for auto-immune diseases are also excluded.
• Patients with active tuberculosis (TB).
• Patients who are pregnant or actively breastfeeding and who do not agree to discontinue breastfeeding before the initiation of radiation treatment planning or bladder cancer therapy.
• Women of childbearing potential and men who do not agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of protocol treatment, and for 5 months after the last study treatment.

Sponsors & Collaborators

• Varian, a Siemens Healthineers Company: lead
• Washington University School of Medicine: collaborator

Study Sites (1)

Washington University, St. Louis

St Louis, Missouri, 63110, United States

Location

Study Officials

• Brian Baumann, MD

  Springfield Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2023
• First Posted: January 26, 2023
• Study Start: February 2, 2023
• Primary Completion: May 9, 2024
• Study Completion: May 9, 2024
• Last Updated: April 21, 2026

Record last verified: 2026-04

Locations

US (1)