Nivolumab for Urothelial carcinoma of the bladder | Invasive bladder cancer

Inclusion criteria

• {"criterion_text":"- Willing and able to provide informed consent\n- 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 (→ 4.4 Pregnancy, contraception and breastfeeding)\n- Age ≥ 18 years\n- Patients with cT2-4aN0-2M0 urothelial bladder cancer, seeking an alternative to radical cystectomy and/or patients who are medically unfit for surgery. Patients with suspected metastatic disease are not eligible.\n- Lymph node metastases should be amenable for inclusion into the radiation field according to the multidisciplinary tumor board and/or follow-up consultations between the treating physician and the radiation oncologist.\n- World Health Organization (WHO) performance Status 0 or 1.\n- Urothelial cancer is the dominant histology (>70%). A small cell component is not allowed.\n- Formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks from diagnostic TUR available.\n- 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 ≤ 2.5 x ULN, ALT ≤2.5 x ULN, Bilirubin ≤1.5 X ULN with an exception for patients with Gilbert’s syndrome (Bilirubin ≤2 X ULN)\n- Negative pregnancy test (βHCG in urine or blood) for female patients of childbearing potential within 2 weeks prior to day 1 of start immunotherapy."}

Exclusion criteria

• {"criterion_text":"- Previous pelvic irradiation\n- Known history of Human Immunodeficiency Virus, active tuberculosis, or other active infection requiring therapy at the time of inclusion.\n- Positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA)\n- Underlying medical conditions that, in the investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of adverse events\n- 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.\n- Use of other investigational drugs four weeks or five half-lives before study drug administration\n- 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.\n- Pregnant and lactating female patients.\n- Major pelvic 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.\n- 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.\n- Upper tract urothelial cancer\n- Extensive carcinoma in situ (CIS) of the bladder\n- Bilateral hydronephrosis\n- Previous intravenous chemotherapy for bladder cancer\n- Contra-indication to one of the study treatment components, or mpMRI\n- 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.\n- Documented history of severe autoimmune disease (e.g. inflammatory bowel disease, myasthenia gravis).\n- Prior CTLA-4 or PD-(L)1 -targeting immunotherapy."}

Primary endpoints

• {"endpoint_text":"- efficacy defined as bladder-intact event-free survival (BI-EFS). Events consist of death by any cause; muscle-invasive recurrence in the bladder or in the ureter, distal of the crossing with the common iliac artery, nodal or distant recurrence, cystectomy, or switch to cisplatin-based chemotherapy.","definition_or_measurement_approach":"BI-EFS defined as bladder-intact event-free survival. Events are defined as: death by any cause; muscle-invasive recurrence in the bladder or in the ureter, distal of the crossing with the common iliac artery; nodal or distant recurrence; cystectomy; or switch to cisplatin-based chemotherapy."}

Secondary endpoints

• {"endpoint_text":"- Overall survival (OS), recurrence-free survival (RFS), feasibility to proceed to CRT, safety, predictive value of ctDNA, QoL, and bladder function","definition_or_measurement_approach":""}

Netherlands

Earliest CTIS Part Ii Submission Date

12-09-2024

Latest Decision Or Authorization Date

10-10-2024

Processing Time Days

28

Number Of Sites

3

Number Of Participants

50

Primary sponsor

Full Name

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"","full_name":"BMS","duties_or_roles":"Source of monetary support","organisation_type":""}