Checkpoint Inhibitor and Radiation Therapy in Bulky, Node-Positive Bladder Cancer

Not Applicable

Terminated

• Conditions: Bladder Cancer
• Interventions: Radiation: personalized ultrafractionated stereotactic ablative radiotherapy

• Registration Number: NCT04779489
• Lead Sponsor: University of Texas Southwestern Medical Center

Brief Summary

Clinically node positive (cN+) bladder cancer carries a poor prognosis, especially in patients who are unable to receive or fail to respond to neoadjuvant chemotherapy. Immune checkpoint inhibitor (ICI) therapy is FDA-approved in advanced bladder cancer for patients unable to receive or failing to respond to platinum-based chemotherapy. The present study seeks to determine if next-generation radiation therapy (personalized ultrafractionated stereotactic ablative radiotherapy, or PULSAR) is feasible and effective in patients receiving ICI for bulky cN+ bladder cancer.

Detailed Description

Patients are eligible for the trial if they have bulky, clinically node-positive (cN+) bladder cancer and have either recently initiated (within ≤ 1 week) or are planned to initiate immune checkpoint inhibitor (ICI) therapy due to either 1) ineligibility for/refusal of platinum-based downstaging chemotherapy; or 2) failure to achieve a complete clinical response to platinum-based downstaging chemotherapy. Patients will initiate PULSAR treatment 1-2 weeks after initiating ICI. PULSAR will be administered in 3 fractions of 12 Gy each (36 Gy total) at 12-16 day intervals and patients will undergo radical cystectomy with bilateral extended pelvic lymph node dissection within 4-8 weeks after completion of PULSAR. ICI therapy will be administered according to the FDA-approved dosing route and schedule and will be continued during PULSAR treatments.

PULSAR treatment will be initiated 1-2 weeks after the patient is initiated on an FDA-approved ICI agent. PULSAR will be administered in 3 fractions of 12 Gy each at 12-16 day intervals. Target areas will include the region of the bladder containing the primary tumor (confirmed, if necessary, on office flexible cystoscopy at UTSW) and to up to five targetable, pathologically enlarged bulky lymph nodes (as deemed feasible by the treating radiation oncologist). Non-enlarged pelvic lymph nodes will be spared to minimize adverse effects on the tumor immune response.

Study Timeline

• Study First Submitted: 2021-02-26
• Study First Submitted QC: 2021-02-26
• Study First Posted: 2021-03-03
• Study Start: 2021-09-06
• Primary Completion: 2023-06-02
• Study Completion: 2023-06-02
• Results First Submitted: 2023-07-14
• Results First Submitted QC: 2023-08-20
• Results First Posted: 2023-08-22
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-11
• Last Update Posted: 2024-02-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PULSAR	personalized ultrafractionated stereotactic ablative radiotherapy	Eligible patients will receive next-generation stereotactic radiotherapy (PULSAR) 30-36 Gy in 3 fractions to the bladder and targetable, pathologically enlarged lymph nodes

Primary Outcome Measures

Name	Time	Method
Protocol Completion	16 weeks	proportion of patients completing PULSAR and undergoing radical cystectomy

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival	2 years	proportion of patients without disease progression

Trial Locations

Locations (1)

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States