This phase II trial studies how well paclitaxel and pembrolizumab works in treating patients with urothelial cancer that has not responded to previous treatment and has spread to other places in the body. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving paclitaxel together with pembrolizumab may be an effective treatment for urothelial cancer.
PRIMARY OBJECTIVES: I. To estimate the overall response rate (ORR) of pembrolizumab combined with paclitaxel. SECONDARY OBJECTIVES: I. To determine the safety and tolerability of pembrolizumab combined with paclitaxel. II. To calculate the progression-free survival (PFS) rate at 6 months. TERTIARY OBJECTIVES: I. To determine the immune effects of pembrolizumab combined with paclitaxel. II. To associate immune effects with tumor response. III. To explore changes in immune-regulatory micro ribonucleic acids (RNAs) as biomarkers of response. OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and paclitaxel IV over 60 minutes on day 1 and 8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up within 30 days and then every 3 months for 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
27
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
Overall Response Rate
The overall response rate will be performed in all patients that are evaluable for efficacy and will have one interim analysis. Overall response is complete response (CR) = Disappearance of all target lesions (PR) = at least a 30% decrease in sum of diameters, taking as reference the baseline sum diameters; stable disease (SD) = neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum diameters while on study; and progressive disease (PD) = at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study based on all target lesions recorded since the treatment started.
Time frame: Up to 6 months
Number of Adverse Events Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
All adverse events will be tabulated and presented by preferred term and/or system organ class and grade. All deaths and serious adverse events will be tabulated.
Time frame: Up to 1 year
Progression Free Survival (Kaplan Meier Method)
The Kaplan Meier methods will be used to estimate progression free survival. The 6-month PFS will be compared to historical rates using a chi-square test. Progressive disease is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study based on all target lesions recorded since the treatment started. The sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression)
Time frame: At 6 months
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