Combining immunotherapy and radiation for bladder cancer treatment

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

This study is testing if giving immunotherapy and radiation together is safe for people with bladder cancer who have had surgery.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Abramson Cancer Center at Penn Medicine (Academic / other)
• Drugs / interventions: nivolumab, chemotherapy, radiation, immunotherapy
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT06586255 on ClinicalTrials.gov

What this trial studies

This Phase I study aims to evaluate the safety of administering concurrent immunotherapy and radiation therapy for patients with urothelial bladder cancer. Participants will receive standard care procedures alongside the experimental combination of treatments, with a focus on monitoring acute toxicity. The study seeks to determine if this dual approach can be safely implemented in patients who have undergone radical cystectomy and pelvic lymph node dissection. The findings may provide insights into the effectiveness of this combined treatment strategy.

Who should consider this trial

Good fit: Ideal candidates include patients with pure or mixed variant urothelial carcinoma who have undergone radical cystectomy and are receiving adjuvant checkpoint inhibitor therapy.

Not a fit: Patients with clinical evidence of residual or recurrent disease or those who do not meet the specific eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes for patients with bladder cancer by enhancing the effectiveness of therapy.

How similar studies have performed: While concurrent immunotherapy and radiation therapy is a novel approach, similar studies have shown promise in other cancer types, suggesting potential for success in this context.

Eligibility criteria

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

Where this trial is running

Philadelphia, Pennsylvania

• University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: John Christodouleas, MD — University of Pennsylvania
• Study coordinator: Project Manager

Conditions Urothelial Carcinoma Bladder; Bladder Cancer