Clinical trial NCT03234153 (phase 2, status: terminated)
Conditions: muscle-invasive bladder cancer
ICD codes: D30.3, C67.5, C67.9, C79.11, C67.0, C67.1, D41.4
Drugs: durvalumab (imfinzi), tremelimumab
SMILES: [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1
Reason stopped: 
    low accrual
  
Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 18 years

          -  Signed Informed Consent Form

          -  ECOG performance status of 0 or 1

          -  Histologically confirmed muscle-invasive urothelial carcinoma of the bladder (T2-T4
             and/or N+). Patients with mixed histologies are required to have a dominant
             transitional cell pattern.

          -  Measurable disease according to RECIST v1.1 criteria

          -  Representative fresh tumor specimen; TURB (transurethral resection of bladder )
             specimens must contain a muscle invasive component (at least T2)

          -  Ineligible to receive cisplatin-based neoadjuvant chemotherapy based on at least one
             of the following criteria:

               -  Creatinin clearance less than 60ml/min (24h urine)

               -  CTCAE Gr ≥ 2 hearing loss

               -  CTCAE Gr ≥ 2 neuropathy

          -  Patient is willing and able to comply with the protocol for the duration of the study
             including undergoing treatment and scheduled visits and examinations including follow
             up

          -  Body weight >30 kg

          -  Adequate hematologic and end-organ function, defined by the following laboratory
             results obtained within 14 days prior the first study treatment:

          -  Absolute neutrophil count (ANC) ≥ 1500 cells/µl

          -  WBC counts > 2500/µl

          -  Platelet count ≥ 100,000/µl

          -  Hemoglobin ≥ 9.0 g/dL

          -  AST, ALT and alkaline phosphatase ≤ 2.5 times the upper limit of normal (ULN)

          -  Serum bilirubin ≤ 1.5 x ULN

          -  INR and aPTT ≤ 1.5 x ULN

          -  Serum creatinine clearance (CrCl) ≥ 40 mL/min using the Cockcroft-Gault equation

          -  Evidence of post-menopausal status or negative urinary or serum pregnancy test for
             premenopausal female. Women will be considered post-menopausal if they have been
             amenorrheic for 12 months without an alternative medical cause.

        Exclusion Criteria:

          -  Known metastatic disease

          -  Intravesical chemo- or biological/immune (BCG) therapy within 6 weeks of first
             treatment dose

          -  Prio treatment with immune checkpoint blockade therapies like anti-CTLA-4, anti-PD1
             and anti-PD-L1 therapeutic antibodies, including durvalumab and tremelimumab

          -  History of autoimmune disease, including but not limited to myasthenia gravis,
             myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,
             inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid
             syndrome, Wegner's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome,
             multiple sclerosis, vasculitis or glomerulonephritis Patients with a history of
             autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are
             eligible for this study. Patients with controlled Type I diabetes mellitus on a stable
             dose of insulin regimen are eligible for this study

          -  Major surgical procedure (as defined by the Investigator) within 28 days prior to the
             first dose of investigational drug.

          -  Female patients who are pregnant or breast feeding as well as male or female patients
             of reproductive potential who are not willing to employ effective birth control from
             screening to 180 days after the last dose of durvalumab + tremelimumab combination
             therapy.

          -  Known allergy or hypersensitivity to any of the investigational study drugs or any of
             the study excipients.

          -  Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical
             study regardless of treatment arm assignment.

          -  Uncontrolled intercurrent illness, including but limited to, ongoing infection,
             symptomatic congestive heart failure, uncontrolled hypertension, unstable angina
             pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic
             gastrointestinal conditions associated with diarrhea, or psychiatric illness/social
             situations that would limit compliance with study requirements, substantially increase
             risk of incurring AEs or compromise the ability of the patient to give written
             informed consent.

          -  Significant cardiovascular disease, such as New York Heart Association cardiac disease
             (Class II or greater), myocardial infarction within the previous 3 months, unstable
             arrhythmias, or unstable angina.

          -  Patients with prior allogeneic stem cell or solid organ transplantation

          -  History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
             pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening
             chest CT scan

          -  Positive test for HIV

          -  Patients with active hepatitis B (defined as having a positive hepatitis B surface
             antigen test at screening) or hepatitis C.

          -  Active tuberculosis

          -  Administration of a living, attenuated vaccine within 4 weeks prior to treatment start

          -  Severe infection within 4 weeks prior to cycle 1, day 1

          -  Treatment with systemic corticosteroids or other systemic immunosuppressive
             medications within 2 weeks prior treatment start or anticipated requirement for
             systemic immunosuppressive medications during the trial. The use of inhaled
             corticosteroids, physiologic replacement doses of glucocorticoids, and
             mineralocorticoids is allowed

          -  Known allergy or hypersensitivity to any of the study drugs or any of the study
             excipients.