Efficacy of Atezolizumab Concurrent With Radiotherapy in Patients With Muscle-invasive Bladder cáncer

Prior treatment

• 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.
• Concurrent treatment with other experimental drugs (within 30 days prior to study entry) or other anti-cancer therapy.
• 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.
• Complete sexual abstinence for 14 days before the start of study treatment to 5 months after completion of the investigational treatment.
• Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), or tubal ligation at least six weeks before taking study treatment.
• Male sterilization (at least 6 months prior to screening). For female subjects on the study the vasectomized male partner should be the sole partner for that subject.

Other illness

• Presence of regional lymph node or metastatic extension of the disease.
• 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) and carcinoma in situ of the cervix.
• Patients with serious uncontrolled infection.
• Has a known history of active BT (Bacillus Tuberculosis).
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• 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.
• Positive test for hepatitis B virus surface antigen (HBVsAg) or hepatitis C virus ribonucleic acid antibody (HCV-Ab) indicating acute or chronic infection.
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• General medical or psychological conditions that would preclude appropriate informed consent or compliance with the protocol.
  • (1) Acceptable methods of effective contraception:
• Intrauterine device or system with a documented failure less than 1%.

Other

• Evidence of tumour-related moderate/severe hydronephrosis unless stented or with nephrostomy to preserve renal function.
• Extensive or multifocal bladder carcinoma in situ (CIS) precluding curative chemoradiotherapy.
• Bulky T3/T4a tumours unsuitable for curative treatment (i.e. \> 5 cm in any dimension). Tumours measures must be done post-TUR via CT scan.
• Women of child-bearing potential unwilling to be abstinent or use effective methods of birth control.
• Double barrier method with spermicide.

• Patients must be 18 years of age or older.
• 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.
• Patients who refuse treatment with cisplatin-based chemotherapy or in whom treatment with cisplatin-based therapy is not appropriate.
• Patients must have ECOG performance status 0 to 2.
• Patients must have adequate bone marrow function as defined by absolute neutrophil count \>1.500/mm3; platelets \>100.000/mm3 and HB ≥ 9g/dl.
• Patients must have adequate renal and liver function as defined by calculated creatinine clearance \>15ml/min.
• Total bilirubin, SGOT (AST) and/or SGPT (ALT) \< 2,5 times the upper limit of normal.
• International Normalized Ration (INR) or Prothrombin Time (PT): ≤1.5 X ULN unless participant is receiving anticoagulant therapy (as long as PT or PTT is within therapeutic range of intended use of anticoagulants).
• Activated Partial Thromboplastin Time (aPTT): ≤1.5 X ULN unless participant is receiving anticoagulant therapy (as long as PT or PTT is within therapeutic range of intended use of anticoagulants).
• Female participant of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to registering the patient. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female participants of childbearing potential should be willing to use two methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 5 months after the last dose of study medication. Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
• 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 (1).
• A paraffin-embedded tumour sample must be available for the associate molecular study.