Phase 1B Study to Assess Safety and Efficacy of Neo-Adjuvant Bladder Urothelial Carcinoma COmbination-immunotherapy (NABUCCO)
Condition: Urothelial Carcinoma
Study Type: Interventional
Clinical Trials Identifier NCT 8-digits: NCT03387761
Sponsor: The Netherlands Cancer Institute
Phase: Phase 1
- Age: minimum 18 Years maximum N/A
- Gender: All
- Willing and able to provide informed consent
- Age ≥ 18 years
- High-risk resectable urothelial cancer (upper urinary tract allowed) defined as stage III UC: cT3-4aN0M0 OR cT1-4aN1-3M0
- Refusal of neoadjuvant/induction cisplatin-based chemotherapy or patients in whom neoadjuvant cisplatin based therapy is not appropriate.
- World Health Organization (WHO) performance Status 0 or
- Urothelial cancer is the dominant histology (>70%).
- Formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks from diagnostic TUR available
- 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.
- For female patients of childbearing potential to use a highly effecting form(s) of contraception (i.e. one that results in a low failure rate [<1% per year] when used consistently and correctly) and to continue its use for 180 days after the last dose of immunotherapy Adequate contraceptive methods are: condom, sterilization, other barrier contraceptive measures preferably in combination with condoms, oral contraceptives, intra-uterine device.
- 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.
- 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.
- 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 (eg, 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 4 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteraemia, 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, or unstable angina.
- Previous intravenous chemotherapy for bladder cancer. Prior chemoradiation is allowed.
- Patients in whom use of a colon segment for urinary diversion is planned
View trial on ClinicalTrials.gov