SGI-110 with cisplatin and gemcitabine chemotherapy in patients with bladder cancer

INTERVENTION: Phase I: Dose‐escalation phase Patients will be entered into sequential dose level cohorts and (at the relevant dose level). Escalating dose level cohorts (4 cohorts are planned) of SGI‐110 + standard gemcitabine/cisplatin chemotherapy for up to 6 cycles of 21 days each. Phase II: Dose expansion phase Patients will be randomised to one of two groups. Group 1: Participants receive 3‐4 cycles (21 days each) of standard GC chemotherapy + SGI‐110 (at the RP2D established in Phase I) Group 2: Participants receive 3‐4 cycles (21 days each) of standard GC chemotherapy only. CONDITION: Topic: Cancer; Subtopic: Bladder Cancer; Disease: Bladder (advanced), Bladder (superficial) ; Cancer ; Bladder cancer PRIMARY OUTCOME: To establish the Recommended Phase II Dose (RP2D) for SGI‐110 when combined with GC within the first year of the study. SECONDARY OUTCOME: 1. Investigation of other potential pharmacodynamic biomarkers for SGI‐110 target is measured at the end of the study; 2. Pharmacokinetics of SGI‐110 when combined with GC are determined within the first year of the study; 3. The pathological complete response rate of bladder cancer patients is measured at the end of the study; 4. Toxicity profile of SGI‐110 when combined with GC is measured throughout the trial INCLUSION CRITERIA: All patients: 1. ECOG performance status of 0 or 1 2. Glomerular filtration rate estimation of = 60 mL/min according to either the Cockcroft and Gault formula or by Cr‐51EDTA or Tc‐99m DTPA clearance 3. Adequate haematological parameters: 3.1. Haemoglobin = 90 g/dL 3.2. Neutrophil count = 1.5 x109/L 3.3. Platelets = 100 x109/L 4. Adequate biochemical parameters 4.1. Bilirubin = 1.5 x ULN 4.2. ALT and ALP = 2.5 x ULN (ALP = 5 x ULN if caused by liver or bone metastases) 5. Aged 16 years or over 6. Life expectancy greater than 3 months 7. Provision of written informed consent Patients in the dose escalation phase: Incurable histologically or cytologically confirmed, locally advanced or metastatic, solid cancer, for which the use of gemcitabine and cisplatin is a clinically appropriate treatment in the view of the local principal investigator. Any number of previous lines of systemic chemotherapy is permitted. Patie