Pre-operative Immunotherapy in Stage II-III Urothelial Cancer

NCT04871594 | Completed Phase 1

• 1 other identifier: M21TUR
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase 1b feasibility study of pre-operative immunotherapy in PD-L1 positive resectable stage II-III urothelial cancer patients. This study can be adapted or expanded based on the results obtained.

Conditions

Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Feasibility of pre-operative nivolumab in PD-L1 positive resectable stage II-III urothelial cancer patients

  Percentage of patients that underwent surgery within 12 weeks after study start will be assessed

  At 12 weeks

Secondary Outcomes (5)

• Pathological complete response rates of nivolumab in PD-L1 positive resectable stage II-III urothelial cancer patients

  At 12 weeks

• Toxicity of pre-operative nivolumab

  From first inusion untill 100 days after the last infusion with nivolumab

• Relapse free survival and overall survival

  From first infusion untill 3 years postoperative

• Monitor peri-surgical complications

  From surgery untill 90 days after surgery

• Translational: effects of nivolumab on the tumor microenvironment

  At 12 weeks

Study Arms (1)

Nivolumab monotherapy

EXPERIMENTAL

Day 1: nivolumab 240 mg Day 22: nivolumab 240 mg Day 43: nivolumab 240 mg

Drug: Nivolumab

Interventions

Nivolumab DRUG

On day 1, 22, and 43 240mg

Also known as: Opdivo

Nivolumab monotherapy

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide informed consent
• Age ≥ 18 years
• Resectable muscle-invasive UC (upper urinary tract allowed), defined as:
• cT2-4aN0M0 OR
• cT1-4aN1-3M0
• World Health Organization (WHO) performance Status 0 or 1.
• Urothelial cancer is the dominant histology (\>70%).
• Formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks from diagnostic TUR available (or equivalent FFPE tumor specimens for upper tract tumors; at least two biopsy cores available).
• PD-L1 status must be determined using the 22C3 pharmDx test. Combined positivity score (CPS) must be \>10.
• 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 as per Cockcroft-Gault formula, AST ≤ 1.5 x ULN, ALT ≤1.5 x ULN, Bilirubin ≤1.5 X ULN
• Negative pregnancy test (βHCG in blood or urine) for female patients of childbearing potential within 2 weeks prior to Day 1 Cycle 1.
• Highly effective contraception for both male and female subjects if the risk of conception exists. Female patients of childbearing potential must comply with contraception methods as requested by the study protocol.

You may not qualify if:

• 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.
• Documented history of severe autoimmune disease (e.g. inflammatory bowel disease, myasthenia gravis).
• Prior CTLA-4 or PD-1/PD-L1-targeting immunotherapy.
• Positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA).
• Underlying medical conditions that, in the investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of adverse events
• Medical condition requiring the use of immunosuppressive medications, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) will be allowed.
• Use of other investigational drugs before study drug administration
• Malignancy, other than urothelial cancer, in the previous 2 years, with a high chance of recurrence (estimated \>10%). Patients with low risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤ 6, and PSA ≤ 10 ng/mL) who are treatment-naive and undergoing active surveillance are eligible.
• Pregnant and lactating female patients.
• Major surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
• Severe infections within 2 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrolment, unstable arrhythmias and unstable angina.
• Previous intravenous chemotherapy for bladder cancer. Prior low-dose sensitizing chemotherapy used for combined modality treatment, or radiation alone, is allowed if patients have recurred after an initial response. Patients with residual disease after (chemo)radiation for bladder cancer are not eligible.
• Patients in whom use of a colon segment for urinary diversion is planned.

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• 4SC AG: collaborator

Study Sites (2)

Antoni van Leeuwenhoek ziekenhuis

Amsterdam, 1066 CX, Netherlands

Location

Radboud Universitair Medisch Centrum

Nijmegen, 6525 GA, Netherlands

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• M.S. van der Heijden, Dr.

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter, open-label phase 1b clinical trial

Study Record Dates

• First Submitted: April 29, 2021
• First Posted: May 4, 2021
• Study Start: August 23, 2021
• Primary Completion: June 2, 2023
• Study Completion: December 30, 2024
• Last Updated: March 5, 2025

Record last verified: 2025-03

Locations

NL (2)