Adjuvant Concurrent Immunotherapy and Radiotherapy for the Treatment of Bladder Cancer

Phase I Safety Trial of Concurrent Adjuvant Immunotherapy and Radiation Therapy for the Treatment of Urothelial Bladder Cancer

The primary objective of this Phase I study is to establish the safety of adjuvant concurrent immunotherapy and radiation therapy for urothelial bladder cancer.

Study Overview

• Status: Recruiting
• Conditions: Bladder Cancer; Urothelial Carcinoma Bladder
• Intervention / Treatment: Radiation: Concurrent Immunotherapy and Radiation Therapy

Detailed Description

Patients in this study will receive the standard of care procedures and follow-up for immunotherapy and radiation therapy. The part of this study that is research is receiving both of these treatments at the same time. Safety will be based on acute toxicity.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Project Manager; Phone Number: 215-662-3790; Email: RadOncCRU@PennMedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Principal Investigator: John Christodouleas, MD
      • Contact: Project Manager; Phone Number: 215-662-3790; Email: RadOncCRU@PennMedicine.upenn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pure or mixed variant urothelial carcinoma

  o Allowable mixed variant subtypes include:

  • squamous differentiation
  • glandular differentiation
  • nested pattern
  • microcystic
  • micropapillary
  • lymphoepthelioma-like
  • plasmacytoid and lymphoma-like
  • sarcomatoid/carcinosarcoma
  • giant cell
  • trophoblastic differentiation
  • clear cell
  • lipid cell
  • undifferentiated
• Radical cystectomy and pelvic lymph node dissection within the prior 48 weeks
• Pathologic T3 or higher stage disease, any N, M0 (AJCC, 7th Ed., Appendix C)
• Receiving adjuvant checkpoint inhibitor therapy

• No clinical evidence of residual or recurrent disease based on the following minimum diagnostic work-up within 3 months of a patient's consent to participate.

  • History and physical examination
  • Chest imaging by x-ray (PA and lateral views), CT scan (with or without IV contrast) or as part of a FDG PET-CT;
  • Axial abdominal and pelvic imaging by MRI (preferably with gadolinium), CT scan (with or without IV contrast) or as part of a FDG PET-CT;
  • Patients with microscopically involved (positive) surgical margins, but no grossly evident residual disease by imaging or physical exam are eligible.

• The patient is a candidate for definitive external beam radiotherapy;

  • No prior radiotherapy to the region of study;
  • No inflammatory bowel disease, active collagen vascular or connective tissue disorders, and no other medical or social contraindications to radiotherapy, as determined by a participating radiation oncologist;
• Age greater than or equal to 18 years
• ECOG performance status: 0-2
• Concurrent non-investigational medications will be permitted
• In addition to diagnostic staging scan, patient will be considered eligible only if he/she has a CT simulation scan that does not show any evidence of recurrent disease
• Informed consent: Patients must have the ability to understand and be willing to sign the study-specific informed consent indicating their understanding of the investigational nature and the risks of this study before any of the protocol related studies are performed (this does not include routine laboratory testing or imaging studies required to establish study eligibility)

Exclusion Criteria:

• Urinary diversion with an orthotopic neobladder
• History of inflammatory bowel disease
• Prior partial or complete small bowel obstruction either before or after radical cystectomy

• Prior radiotherapy to the pelvis;

  o Prior radiation therapy for a different cancer or disease process is allowed, provided there will be no overlap of radiation therapy fields between the participant's prior and current course of radiation therapy, radiotherapy was completed more than four weeks from enrolling in this study.

• Planned concurrent chemotherapy or other investigational drug to be given with radiation treatments

  o Prior chemotherapy or investigational drug for bladder cancer or a different cancer is allowed, provided that:

  • The therapy was completed more than two weeks prior to the start of adjuvant pelvic radiation
  • The participant has recovered to Grade ≤1 toxicity from agents previously administered, excluding toxicities that would not be expected to impact eligibility for radiation therapy including but not limited to neuropathy, alopecia and hearing loss.
• Subtotal surgical resection with clinically evident residual disease by physical exam or axial imaging.
• Prior or concurrent second invasive malignancy that, in the judgment of the investigator, may affect interpretation of the results.

• Known severe, active co-morbidity, defined as follows:

  o Any clinically significant unrelated systemic illness, medical condition, or other factor, which at the discretion of the Principal Investigators, would interfere in the safe and timely completion of study procedures, compromise the patient's ability to tolerate the protocol therapy, or is likely to interfere with the study procedures or results.

• Patients who experienced Grade 3+ GI toxicity due to surgery or nivolumab prior to enrollment in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Concurrent Immunotherapy and Radiation Therapy; Subjects will receive the standard of care procedures and follow-up for immunotherapy and radiation therapy. The part of this study that is research is receiving both of these treatments at the same time.	Radiation: Concurrent Immunotherapy and Radiation Therapy; Radiation therapy will begin between 12 to 18 weeks from the start of adjuvant nivolumab. Patients will receive radiation therapy for about 6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of concurrent adjuvant immunotherapy and radiation therapy	The primary study endpoint is acute grade 3 or higher pelvic radiation related toxicity. A toxicity will be classified as related to pelvic radiation if the toxicity involves or is the result of effects on tissues that are within the 50% isodose bath of the radiation treatment as defined on the radiation treatment planning simulation scan. Toxicities will be graded by CTCAE Version 5.0. Concurrent adjuvant immunotherapy and radiation will be deemed safe if it is likely (i.e. a posterior probability of 50% or greater) that the acute grade 3 or higher pelvic radiation related toxicity rate is <20%.	Within 18 weeks from start of radiation therapy

Collaborators and Investigators

• Sponsor: Abramson Cancer Center at Penn Medicine
• Investigators: Principal Investigator: John Christodouleas, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: September 4, 2024
• First Submitted That Met QC Criteria: September 4, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urologic Neoplasms; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Therapeutics; Radiotherapy
• Other Study ID Numbers: UPCC 16824; 856691 (Other Identifier: University of Pennsylvania Institutional Review Board)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No