Urothelial Carcinoma MedDRA version: 21.1 Level: LLT Classification code 10022877 Term: Invasive bladder cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: avelumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: AVELUMAB
CAS Number: 1537032-82-8
Concentration unit: mg/ml milligram(s)/millilitre
Concentration
Sponsors
Insitut Jules Bordet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Age = 18 years old 2) Must have histologically confirmed muscle invasive urothelial carcinoma (transitional cell carcinoma) or urothelial carcinoma with mixed histology of the bladder, renal pelvis or ureters. Stage permitted: T2, T3 or T4a. T stage is based on the standard of care transurethral resection of the bladder tumour (TURBT) sample 3) Subjects may have nodal disease (Nx, N0, N1 or N2) at imagery but there must be no evidence of distant metastases (M0) 4) Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG). 5) Be a medically appropriate candidate for surgery as determined by an attending urologist 6) Adequate bone marrow function as defined below - Absolute neutrophil count =1500/µL or 1.5x109/L - Hemoglobin = 9 g/dL - Platelets =100,000/µL or 100x10 9/L 7) Adequate liver function as defined below - Serum total bilirubin = 1.5 x ULN. In case of known Gilbert’s syndrome =65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1) Metastatic disease (M1) 2) Has had prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy for urothelial carcinoma (previous BCG injections permitted) 3) Prior treatment with drug specifically targeting T-cell co-stimulation or checkpoint pathways 4) Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses = 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) 5) Has an active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Subjects with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. 6) Has had a prior organ transplantation including allogenic stem-cell transplantation. 7) Has an active infection requiring systemic therapy (antibiotics) 8) Has a known history of Human Immunodeficiency Virus (HIV) or known acquired immunodeficiency syndrome. 9) Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA is detected) (test to be performed except if there are results available from less than 1 year). 10) Has received vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines such as influenza vaccine. 11) Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 28 days prior to study registration 12) History of prior invasive malignancy within 2 years (exception of adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localised prostate cancer or ductal carcinoma in situ) 13) Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade = 3) 14) Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (1); however, alopecia, sensory neuropathy Grade =2, or other Grade =2 not constituting a safety risk based on investigator’s judgment are acceptable. 18) Other severe acute chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with the study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. Exclusion criterion spe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective: To assess the efficacy of Avelumab (anti-PD-L1) associated to different cytotoxic agents or in monotherapy in patients with non-metastatic MIBC as measured by the pathologic complete response rate (ypT0/Tis ypN0) following neoadjuvant treatment;Secondary Objective: To assess the safety and tolerability of the regimens used;Primary end point(s): To determine the pathologic complete response (ypT0/Tis ypN0) following neoadjuvant treatment in patients with non-metastatic MIBC. Outcome measure: Pathological complete response is defined as the absence of invasive carcinoma (ypT0/Tis) disease and the absence of microscopic lymph node metastases (ypN0) on the final surgical specimen.;Timepoint(s) of evaluation of this end point: end of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To determine the pathologic response rate (<ypT2N0) following neoadjuvant treatment in patients with non-metastatic MIBC. Outcome measure: Pathologic response is defined as the absence of muscle invasive carcinoma (<ypT2N0 disease) on the final surgical specimen. - To assess the toxicity profile Outcome measure: using the adverse events reported during the study according to NCI CTCAE v4.03;Timepoint(s) of evaluation of this end point: end of the study | — |
Countries
Belgium, France
Contacts
Public ContactCTSU
Institut Jules Bordet
Outcome results
None listed