MUSCLE-INVASIVE BLADDER CANCER MedDRA version: 20.0 Level: LLT Classification code 10022877 Term: Invasive bladder cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Tecentriq
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
Current Sponsor code: RO5541267
Sponsors
Grupo Español de Oncología Genitourinaria (SOGUG)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must be 18 years of age or older. 2. Patients have histologically-confirmed diagnosis of muscle-invasive urothelial carcinoma of the bladder, in clinical stages T2-4a N0 M0, who are not candidates for radical cystectomy by medical reasons, refusal or patient’s choice. 3. Patients are “unfit” to Cisplatin defined as one of the following criteria: ? WHO or ECOG performance status 2 or Karnofsky performance status 60-70%. ? Creatinine clearance (calculated or measured) less than1 mL/s. ? CTCAE version 5, grade 2 or above auditive hearing loss. ? CTCAE version 5, grade 2 or above peripheral neuropathy. ? NYHA class III heart failure. 4. Patients must have ECOG performance status 0 to 2. 5. Patients must have adequate bone marrow function as defined by absolute neutrophil count >1.500/mm3; platelets >100.000/mm3 and HB = 9g/dl. 6. Patients must have adequate renal and liver function as defined by calculated creatinine clearance >15ml/min. 7. Total bilirubin, SGOT (AST) and/or SGPT (ALT) 1 year.* 13. Male participants should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.* 14. A paraffin-embedded tumour sample must be available for the associate molecular study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 14
Exclusion criteria
Exclusion criteria: 1. Previous treatment with radiotherapy to the bladder, systemic chemotherapy or immune checkpoint inhibitors. Prior intravesical BCG treatment for non-muscle invasive bladder cancer is allowed. 2. Presence of regional lymph node or metastatic extension of the disease. 3. Concurrent treatment with other experimental drugs (within 30 days prior to study entry) or other anti-cancer therapy. 4. History of prior malignancies within the preceding 5 years other than previously treated basal cell carcinoma of the skin, non-muscle invasive bladder cancer, incidental prostate carcinoma Stage T1a well differentiated prostatic carcinoma in men (Gleason = 3+3, PSA 5 cm in any dimension). 8. Patients with serious uncontrolled infection. 9. Has a known history of active BT (Bacillus Tuberculosis). 10. Has known history of, or any evidence of active, non-infectious pneumonitis. 11. Autoimmune diseases other than vitiligo, type I diabetes mellitus, residual hypothyroidism requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger. 12. Positive test for hepatitis B virus surface antigen (HBVsAg) or hepatitis C virus ribonucleic acid antibody (HCV-Ab) indicating acute or chronic infection. 13. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). 14. Subjects with a condition requiring systemic treatment with either corticosteroids (equivalent to > 10 mg/day prednisone) or other immune-suppressive medications within 14 days of study drug administration. 15. Women of child-bearing potential unwilling to be abstinent or use effective methods of birth control. 16. General medical or psychological conditions that would preclude appropriate informed consent or compliance with the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Tras el final del tratamiento (16 weeks).;Main Objective: Efficacy of atezolizumab concurrent with radiotherapy;Primary end point(s): Pathological complete response defined as a response of grade 5 according to Miller and Payne criteria; Secondary Objective: • To evaluate overall survival (OS). • To evaluate disease specific survival (DSS). • To evaluate disease free survival (DFS). • To evaluate bladder intact disease-free survival (BIDFS). • To calculate the number of patients with muscle invasive and non-muscle invasive local failure (LF). • To determine the rate of distance metastases defined as the percentage of patients who develop metastases. • To determine to the rate of patients with bladder preserved. • To determine to the rate of immediate or late salvage cystectomy. • The safety profile and tolerability of the combination of atezolizumab with concurrent radiotherapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Continiusly along the study visits.; Secondary end point(s): -Overall survival: Time from the date of the beginning of protocol therapy to the date of death due to any cause. -Disease specific survival: Time from start of treatment to the date of having evidence of distant metastases, nodal recurrence or recurrence within the radiotherapy field that could be salvaged in a curative fashion, what happens first. -Disease free survival: Time from the date of start of protocol therapy to the date of recurrence of muscle invasive or non-invasive bladder carcinoma or metastases, what happens first. -Bladder-intact disease-free survival: Time from the date of initiation of protocol therapy until the development of MIBC recurrence, regional pelvic recurrence, distant metastases, bladder cancer-related death or cystectomy, what happens first. -Muscle invasive and non-muscle invasive local failure defined as patients that do not achieve a pCR defined as a response of grade 5 according to Miller and Payne criteria and documented tumour recurrence after pCR -Rate of distant metastases: Percentage of patients who develop distant metastases. Defined as lymphonodal involvement above the bifurcation of the iliac vessels or in inquinal regions and metastases resulting from hematogenous spread. -Rate of patients with bladder preserved at the time of the biopsy of the tumour performed between one and two months after the last dose of atezolizumab. -Rate of immediate or late salvage cystectomy. Immediate will be evaluated at the time of the biopsy of the tumour performed between one and two months after the last dose of atezolizumab and late will be evaluated during the follow-up. -Collection of any AEs and SAEs. | — |
Countries
Spain
Contacts
Public ContactDepartamento de Ensayos Clínicos
Dynamic
Outcome results
None listed