muscle-invasive bladder cancer (MIBC) MedDRA version: 20.0 Level: PT Classification code 10005003 Term: Bladder cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Hellenic Genitourinary Cancer Group (HGUCG)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed bladder carcinoma with invasion of muscularis propria. 2. Urothelial, squamous and glandular histological subtypes are acceptable 3. Clinical stage cT2-T4a; N0, M0according to the 8th edition of the American Joint Committee on Cancer (AJCC), (Appendix III) 4. Patients must be judged to be medically inappropriate for radical cystectomy or patients who refuse radical cystectomy. 5. Age 18 years. 6. Performance status ? 1 based on the ECOG (Eastern Cooperative Oncology Group) scale (Appendix II). 7. Patients must have undergone a vigorous TURB by an urologist. Bimanual evaluation and tumor mapping prior to enrollment as specified in Lipiodol labeled to the tumor bed by the urologist during TURB is advised but is not mandatory for enrollment (Appendix IV). 8. Protocol treatment should begin within 3 to 8 weeks of the most recent TURB. 9. Chest/Abdominal/ pelvic computed tomography (CT) scan and/or magnetic resonance imaging (MRI) scan within 8 weeks prior to randomization. 10. Bone scan and brain imaging should be performed within 28 days prior to randomization in the case of clinical suspicion of bone or brain metastases to rule out metastatic disease prior to enrollment on study. 11. Adequate hematologic, renal, and liver function (using CTCAE v4). (All baseline laboratory requirements will be assessed and should be obtained within 14 days prior to randomization) a. WBC 2000/µL b. Neutrophils 1500/µL c. Platelets 100 x 103/µL d. Hemoglobin 9.0 g/dL e. Creatinine clearance (CrCl) 40 mL/min (using the Cockcroft-Gault formula) f. AST 3 x ULN g. ALT 3 x ULN h. Total Bilirubin 1.5 x ULN (except in subjects with Gilbert Syndrome, who can have total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, prostate cancer with evidence of undetectable Prostate Specific Antigen (PSA) or carcinoma in situ of the prostate, cervix or breast. 2. Previous systemic chemotherapy or prior biologic agents within 4 weeks, or intravesical Bacillus Calmette-Guerin (BCG) within 6 weeks of the first dose of study treatment. 3. Prior treatment with any PD-1 or PDL-1 inhibitor or anti CTLA4 agent 4. Previous pelvic radiation therapy. 5. Patients with inherited syndromes associated with hypersensitivity to ionizing radiation (e.g., ataxia-telangiectasia, Nijmegen breakage syndrome). 6. Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results. 7. Any history of inflammatory bowel disease 8. History of abdominal fistula 9. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration 10. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. 11. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus (ribonucleic acid or HCV antibody) indicating acute or chronic infection prior to randomization. 12. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) prior to randomization. 13. Allergies and Adverse Drug Reaction a) History of allergy to study drug components. b) History of severe hypersensitivity reaction to any monoclonal antibody 14. Pregnant or nursing women; this exclusion is necessary because treatment involves unforeseeable risks to the participant and to the embryo or fetus. 15. Men or women of childbearing potential who are sexually active and are not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare locoregional control rate at 2-years between patients with MIBC receiving or not receiving nivolumab in addition to chemoradiotherapy ;Secondary Objective: 1.To study the safety of the addition of nivolumab to chemoradiotherapy in patients with MIBC 2.To compare 2-year bladder cancer failure-free (BCFF) rates, defined as distant metastasis free survival (MFS) AND/OR locoregional failure (defined as in primary objective) 3.To compare median overall survival (OS) in patients with MIBC receiving or not receiving nivolumab in addition to chemoradiotherapy 4.Assess the effect of combined treatment on the quality of life Correlative studies of outcomes with PD-L1expression and with lymphocytic populations in the environment of the tumor ion in English and add any other language that is applicable;Primary end point(s): | — |
Countries
Greece
Contacts
Public ContactScientific supervisor
Hellenic Genitourinary Cancer Group (HGUCG)
Outcome results
None listed