Clinical trial NCT03106610 (phase 1, status: terminated)
Conditions: bladder cancer
ICD codes: D30.3, C67.5, C67.9, C79.11, C67.0, C67.1, D41.4
Drugs: nivolumab
SMILES: [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1
Reason stopped: 
    slow accrual
  
Eligibility criteria:

        Inclusion Criteria:

          1. Patients included in the study must be >/= 18 years old.

          2. Histological or cytological evidence of transitional cell carcinoma or carcinoma in
             situ of the urothelium involving the bladder or prostatic urethra following treatment
             with BCG with the recommendation to proceed for cystectomy. Minor histologic variants
             (< 50% overall) are acceptable. Diagnosis must be within 1 year of study entry.

          3. Patent must have BCG unresponsive non-muscle-invasive bladder cancer defined as:
             Persistent or recurrence of CIS within 12 months, or recurrence of CIS with Ta/T1
             papillary disease within 12 months, or recurrence of high grade Ta or T1 papillary
             disease alone within 6 months of receiving at least two courses of intravesical BCG
             (at least five of six induction doses and at least two doses of either a maintenance
             course of BCG or a 2nd re-induction of BCG; or T1 high-grade disease at the first
             evaluation following induction of BCG alone (at least five of six induction doses).

          4. Subjects must have received intravesical treatment with at least two doses of BCG
             within six months of nivolumab treatment initiation.

          5. Evaluable tumor tissue (archived or new biopsy) must be available for pre-treatment
             biomarker analysis and baseline immune monitoring studies

          6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.

          7. Screening laboratory values must meet the following criteria and must be obtained
             within 14 days prior to first dose: a) WBC >/= 2000/µL; b) Neutrophils >/= 1500/µL; c)
             Platelets >/= 100 x 10^3/mcl; d) Hemoglobin >/= 9.0 g/dL; e) AST and ALT </= 3 x ULN;
             f) Total Bilirubin </= 1.5 x ULN (except subjects with Gilbert Syndrome, who can have
             total bilirubin < 3.0 mg/dL)

          8. Inclusion 6) continued; g.Serum creatinine </=1.5 x ULN or creatinine clearance (CrCl)
             >/=30 mL/min (using the Cockcroft-Gault formula): 1) Female CrCl = (140 - age in
             years) x weight in kg x 0.85 / 72 x serum creatinine in mg/dL; 2) Male CrCl = (140 -
             age in years) x weight in kg x 1.00 / 72 x serum creatinine in mg/dL

          9. Ability to understand and willingness to sign a written informed consent document.

         10. Females of childbearing potential who are sexually active with a non-sterilized male
             partner and non-sterilized males must use a highly effective method of contraception
             for 28 days prior to the first dose of investigational product, and must agree to
             continue using such precautions for 180 days after the final dose of investigational
             product; cessation of contraception after this point should be discussed with a
             responsible physician. Periodic abstinence, the rhythm method, and the withdrawal
             method are not acceptable methods of contraception. They must also refrain from egg
             cell donation for 180 days after the final dose of investigational product;

         11. Inclusion 9) continued; a) Females of childbearing potential are defined as those who
             are not surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or
             complete hysterectomy) or postmenopausal (defined as 12 months with no menses without
             an alternative medical cause)

         12. Inclusion 9) continued; b) A highly effective method of contraception is defined as
             one that results in a low failure rate (ie, less than 1% per year) when used
             consistently and correctly. The acceptable methods of contraception are: Barrier
             Method (e.g. male condom with spermicide, copper T intrauterine device, or
             levonorgestrel-releasing intrauterine system - Mirena®) or Hormonal Methods (e.g.
             implants, hormone shot or injection, combined pill, minipill, or patch).

        Exclusion Criteria:

          1. Patients with high risk muscle invasive urothelial carcinoma (hydronephrosis, palpable
             mass on examination under anesthesia,muscle invasive urothelial carcinoma with
             lymphovascular invasion on pathologic specimen, >T3 disease) or those with lymph node
             positive or metastatic disease are to be excluded.

          2. Any serious or uncontrolled medical disorder that, in the opinion of the investigator,
             may increase the risk associated with study participation or study drug
             administration, impair the ability of the subject to receive protocol therapy, or
             interfere with the interpretation of study results.

          3. Prior malignancy active within the previous 3 years except for locally curable cancers
             that have been apparently cured, such as basal or squamous cell skin cancer, prostate
             cancer without evidence of PSA progression or carcinoma in situ such as the following:
             gastric, prostate, cervix, colon, melanoma, or breast for example.

          4. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo,
             type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only
             requiring hormone replacement, psoriasis not requiring systemic treatment, or
             conditions not expected to recur in the absence of an external trigger are permitted
             to enroll.

          5. Subjects with a condition requiring systemic treatment with either corticosteroids (>
             10 mg daily prednisone equivalents) or other immunosuppressive medications within 14
             days of study drug administration. Inhaled or topical steroids and adrenal replacement
             doses > 10 mg daily prednisone equivalents are permitted in the absence of active
             autoimmune disease.

          6. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic
             T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody, anti-CD137, or any other
             antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint
             pathways.

          7. All toxicities attributed to prior anti-cancer therapy other than neuropathy, alopecia
             and fatigue must have resolved to Grade 1 (NCI CTCAE version 4) or baseline before
             administration of study drug. Subjects with toxicities attributed to prior anti-cancer
             therapy which are not expected to resolve and result in long lasting sequelae, such as
             neuropathy after platinum based therapy, are permitted to enroll. Neuropathy must have
             resolved to Grade 2 (NCI CTCAE version 4).

          8. Treatment with any chemotherapy, radiation therapy, biologics for cancer, or
             investigational therapy within 28 days of first administration of study treatment.

          9. Physical and Laboratory Test Findings; a) Positive test for hepatitis B virus surface
             antigen (HBV sAg) or hepatitis C virus ribonucleic acid (RNA) or hepatitis C antibody
             (HCV antibody) indicating acute or chronic infection; b) Known history of testing
             positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency
             syndrome (AIDS).

         10. Allergies and Adverse Drug Reaction; a) History of allergy to study drug components;
             b) History of severe hypersensitivity reaction to any monoclonal antibody.

         11. Sex and Reproductive Status; a) Women of childbearing potential (WOCBP) who are
             pregnant or breastfeeding; b) Women with a positive pregnancy test at enrollment or
             prior to administration of study medication

         12. Prisoners or subjects who are involuntarily incarcerated

         13. Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical (eg, infectious disease) illness.