This is a phase 2 trial seeking to define the safety and activity of gemcitabine, cisplatin, plus nivolumab as neoadjuvant therapy in patients with muscle-invasive bladder cancer and to define the role of clinical complete response in predicting benefit in patients opting to avoid cystectomy.
|Overal Status||Start Date||Phase||Study Type|
|Recruiting||July 13, 2018||Phase 2||Interventional|
Primary Outcome 1 - Measure: Determine the clinical complete response rate (cT0 or cTa) with gemcitabine, cisplatin, plus nivolumab
Primary Outcome 1 - Time Frame: 24 months
Primary Outcome 2 - Measure: Determine the ability of clinical complete response (cT0 or cTa) to predict benefit from treatment.
Primary Outcome 2 - Time Frame: 24 months
- ECOG Performance Status of ≤ 1 within 28 days prior to registration.
- Histological evidence of clinically localized muscle-invasive urothelial cancer of the
bladder (i.e., ct2-4n0m0). candidate for cystectomy as per treating physician.
- Demonstrate adequate organ function per listed criteria:
- Absolute Neutrophil Count (ANC): ≥ 1.5 x 10^9/L
- Hemoglobin (Hgb): ≥ 9 g/dL
- Platelets: ≥ 100 x 10^9/L
- Calculated creatinine clearance: Creatinine ≤ 1.5 or creatinine clearance ≥ 60 mL/min
- Bilirubin: ≤ 1.5 × upper limit of normal (ULN) (except subjects with Gilbert Syndrome,
who can have total bilirubin < 3.0 mg/dL)
- Aspartate aminotransferase (AST) : ≤ 3 × ULN
- Alanine aminotransferase (ALT) : ≤ 3 × ULN
- All subjects must have adequate archival tissue submitted prior to registration (i.e.,
at least 15 unstained slides or paraffin block).
- Women of childbearing potential (WOCBP) must use appropriate method(s) of
- Women of childbearing potential must have a negative serum or urine pregnancy within 7
days prior to C1D1.
- Men who are sexually active with WOCBP must use any contraceptive method with a
failure rate of less than 1% per year.
- Prior treatment with systemic chemotherapy for muscle-invasive urothelial cancer of
- Active infection requiring systemic therapy
- Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
mother is being treated on study).
- 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.
- Prior malignancy active within the previous 3 years except for locally curable cancers
that have been apparently cured.
- 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
- 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
- Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or
any other antibody or drug specifically targeting T-cell co-stimulation or immune
- Grade ≥ 2 neuropathy (NCI CTCAE version 4).
- Prior radiation therapy for bladder cancer
- 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
- Known history of testing positive for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (AIDS).
- Evidence of interstitial lung disease or active, non-infectious pneumonitis.
- Solid organ or allogeneic stem cell transplant
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Matthew Galsky, MD
Role: Principal Investigator
Affiliation: Icahn School of Medicine at Mount Sinai
Name: Matthew Galsky, MD
|Icahn School of Medicine: Tisch Cancer Institute at Mount Sinai Medical Center
New York, New York 10029
Matthew Galsky, M.D.