Phase 1B Study to assess safety and efficacy of Neo-Adjuvant Bladder Urothelial Carcinoma COmbination-immunotherapy (NABUCCO)

Recruiting

• Conditions: 10038364; Urothelial cancer; Urothelial carcinoma

• Registration Number: NL-OMON55844
• Lead Sponsor: Antoni van Leeuwenhoek Ziekenhuis

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 54

Inclusion Criteria

High-risk resectable urothelial cancer (upper urinary tract allowed), defined
as stage III UC:
- cT3-4aN0M0 OR
- >=T1-4aN1-3M0
- Patients who refuse neoadjuvant/induction cisplatin based chemotherapy or in
whom neoadjuvant cisplatin based therapy is not appropriate
- Age > 18 years
- World Health Organization (WHO) performance Status 0 or 1.
- Screening laboratory values must meet the following criteria: WBC >=
2.0x109/L, Neutrophils >=1.0x109/L, Platelets >=100 x109/L, Hemoglobin >=5.5
mmol/L, GFR>30 ml/min, AST <= 2.5 x ULN, ALT <=2.5 x ULN, Bilirubin <=1.5 X ULN
- Negative pregnancy test within 2 weeks of Day 1 Cycle 1 for female patients
of childbearing potential.

Exclusion Criteria

- No high risk profile as defined by criteria
- Previous intravenous chemotherapy for bladder cancer i.v. Prior
chemoradiation is allowed.
- Subjects with active autoimmune disease in the past 2 years. Patients with
diabetes mellitus, properly controlled hypothyroidism or hyperthyroidism,
vitiligo, psoriasis or other mild skin disease can still be included.
- Prior CTLA-4 or PD-1/PD-L1-targeting immunotherapy.
- Pregnant and lactating female patients.
- Known history of Human Immunodeficiency Virus, positive tests for Hepatitis B
surface antigen or Hepatitis C ribonucleic acid (RNA), active tuberculosis, or
other active infection requiring therapy at the time of inclusion.
- Patients in whom use of a colon segment for urinary diversion is planned

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Main study parameter/endpoint<br /><br><br /><br>Safety (only for cohort 1)<br /><br>The primary endpoint of this trial is the percentage of patients having surgery<br /><br><12 weeks after study enrollment, as this is an endpoint that is clinically<br /><br>meaningful for this population. We set the desired resection rate by 12 weeks<br /><br>at 90% of patients. The treatment can be considered sufficiently safe if 20 or<br /><br>more patients have their resection <12 weeks. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary study parameters/endpoints<br /><br><br /><br>Translational<br /><br>The main testable hypothesis is that a significant percentage of nonresponse<br /><br>can be explained by immune-inhibitory processes. Absence of immune infiltrates,<br /><br>presence of significant numbers of regulatory T-cells and presence of<br /><br>significant numbers of myeloid-derived suppressor cells will be compared<br /><br>between responders and nonresponders.<br /><br><br /><br>Efficacy<br /><br>The efficacy will be defined as the percentage of pathological complete<br /><br>response (pCR) at cystectomy.<br /><br><br /><br>Translational<br /><br>Explore how the (dys)functional state of the tumor-specific T cells is altered<br /><br>by sequenced combination therapy.<br /><br><br /><br>Safety<br /><br>Provide an estimate of >=grade 3 immune-related toxicity in the ipi3/nivo1 and<br /><br>ipi1/nivo3 cohorts</p><br>