A Study of Mitomycin-c/ Capecitabine ChemoRadiotherapy Combined With Nivolumab Monotherapy or Ipilumimab and Nivolumab, as Bladder Sparing Curative Treatment for Muscle Invasive Bladder Cancer: the CRIMI Study

Exclusion Criteria

• •Has DPD deficiency.
• •Has concurrent extra-vesical (i.e. urethra, ureter or renal pelvis) urothelial cell carcinoma of the urothelium. Patients who have involvement of the prostatic urethra with urothelial cell cancer may be included if the location can be safely incorporated in the radiation field.
• •Extensive or multifocal bladder carcinoma in situ (CIS) precluding curative chemoradiotherapy.
• •Evidence of distant metastatic disease on a CT or FDG PET/CT chest/abdomen/pelvis performed within 28 days prior to study entry. Up to 3 metastatic lymphnodes in the pelvis (below the common iliac arteries) are allowed, if these can be incorporated in the radiotherapy field.
• •Prior pelvic lymph-adenectomy
• •Prior pelvic radiotherapy
• •Has had prior intravenous chemotherapy, targeted small molecule therapy, or radiation therapy for treatment of bladder cancer. Prior intravesical use of BCG and MMC is permissible.
• •Unsuitable for concurrent MMC / capecitabine based ChRT based on pre-existing medical conditions.
• •Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of treatment.
• •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy over 10mg daily prednisone (or equivalent) or any other form of immunosuppressive therapy within 14 days prior to registering the patient. Patients with adrenal insufficiency receiving replacement dose steroids are allowed on the trial.
• •Has a known history of active TB (Bacillus Tuberculosis)
• •Hypersensitivity to nivolumab and/or ipilimumab or any of its excipients.
• •Prior or concurrent known additional malignancy of any site unless disease free for 5 years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer, Stage T1a well differentiated prostatic carcinoma in men (Gleason = 3+3, PSA \<5)
• •Has any history of active autoimmune disease, Stevens-Johnson syndrome or Guillain-Barre. Exceptions to this are:
• •1. Patients with autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone
• •2. Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen
• •Has known history of, or any evidence of active, non-infectious pneumonitis.
• •Has an active infection requiring systemic therapy.
• •Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• •Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• •Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• •Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
• •Has an Human Immunodeficiency Virus (HIV) infection with a PCR detectable viral load.
• •Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• •Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.