Gemcitabine plus cisplatin is standard treatment for advanced urothelial cancer. Ipilimumab has shown intriguing activity as neoadjuvant therapy in patients with clinically localized bladder cancer undergoing radical cystectomy. The combination of gemcitabine, cisplatin, plus ipilimumab may build on the chemosensitivity of urothelial carcinoma to produce more durable responses and improved outcomes.
OUTLINE: This is a multi-center study Gemcitabine 1000 mg/m2 Days 1 \& 8 Cisplatin 70 mg/m2 Day 1 Ipilimumab 10 mg/kg Day 1 (start cycle 3) Treatment during the induction phase will be administered in six 21-day cycles. During cycles 1 and 2, gemcitabine plus cisplatin will be administered WITHOUT ipilimumab. During cycles 3-6, combination therapy with gemcitabine, cisplatin, plus ipilimumab will be administered. Patients without evidence of disease progression (by irRC) after completion cycle 6 will continue single-agent ipilimumab maintenance every 3 months. Karnofsky performance status (KPS) ≥ 80% within 14 days prior to registration for protocol therapy. Life Expectancy: Not Specified Hematopoietic: * White blood cell count (WBC) ≥ 3.5K/mm3 * Hemoglobin (Hgb) ≥ 9 g/dL * Platelets ≥ 100K/mm3 * Absolute neutrophil count (ANC) ≥ 1.5k/mm3 Hepatic: * Bilirubin ≤ 1.5 times x Upper Limit of Normal (ULN) (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL) * Aspartate aminotransferase (AST, SGOT) ≤ 2.5 x ULN. NOTE: If the patient has liver metastases present, then ≤ 5 x ULN Renal: * Calculated creatinine clearance of ≥ 55 cc/min using the Cockcroft-Gault formula Cardiovascular: Not Specified
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Gemcitabine 1000 mg/m2 Days 1 \& 8 (all cycles)
Cisplatin 70 mg/m2 Day 1 (all cycles)
Ipilimumab 10 mg/kg Day 1 (start cycle 3)
City of Hope: Duarte
Duarte, California, United States
IU Health Goshen Hospital
Goshen, Indiana, United States
Indiana University Melvin & Bren Simon Cancer Center
Indianapolis, Indiana, United States
IU Health Central Indiana Cancer Centers
Indianapolis, Indiana, United States
Median Overall Survival
To determine the median overall survival of patients with advanced/metastatic urothelial cancer treated with gemcitabine, cisplatin, plus ipilimumab, calculated from the date of registration until the date of final analysis, projected to be 48 months from the start of the study.
Time frame: 48 months
Progression-Free Survival
To determine the progression-free survival (using irRC and RECIST v1.0) of patients with advanced/metastatic urothelial carcinoma treated with gemcitabine, cisplatin, and ipilimumab. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions". Progression is definied by IrRC as "at least 25% increase in tumor burden compared with nadir (at any single time point) in two consecutive observations at least 4 wk apart."
Time frame: 12 months
Best Overall Response Rate
To determine the best overall response rate to treatment with gemcitabine, cisplatin, plus ipilimumab, per RECIST 1.1 criteria.
Time frame: 12 months
Number of Adverse Events Experienced by Patients
To determine the safety of treatment with gemcitabine, cisplatin, plus ipilimumab. The highest grade adverse event for each subject is presented.
Time frame: 12 months
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Nebraska Cancer Specialists
Omaha, Nebraska, United States
Tisch Cancer Institute at Mount Sinai Medical Center
New York, New York, United States
Texas Oncology, PA
Dallas, Texas, United States
Virginia Oncology Associates
Norfolk, Virginia, United States