Cabazitaxel in Patients With Urothelial Carcinoma Who Have Disease Progression Following Platinum-Based Chemotherapy

Phase 2

Completed

Interventions: Drug: Cabazitaxel
Drug: Neulasta
Procedure: CT Scan
Biological: Blood Draw

Brief Summary: There is no accepted standard chemotherapy approved for use in the second line for patients with advanced urothelial carcinoma whose cancer has progressed on combination chemotherapy including either cisplatin or carboplatin. The chemotherapy class called taxanes, either as single agents or in combination, have demonstrated modest efficacy in small studies. Cabazitaxel is an agent in the taxane family designed to be active in the setting of acquired multi-drug resistance that arises in some tumors. The objective of this study is to evaluate the safety and efficacy of this agent in patients with urothelial carcinoma refractory compared to combination platinum based chemotherapy.

Detailed Description: This is a single-arm, open-label study, meaning all patients will be treated in the same fashion with the investigational agent. Scans will be performed every 3 cycles of treatment, and patients will be withdrawn from study in the event of progression or drug intolerance as defined within the protocol.

Treatment will be administered on an outpatient basis. No investigational or commercial agents or therapies other than those described below may be administered with the intent to treat the patient's malignancy.

The length of each cycle is 21 days. For the first cycle of treatment, cabazitaxel will be dosed at 20 mg/m2. During cycle 1, complete blood counts will be performed on days 8 and 15, and dosing on Day 1 cycle 2 will depend upon the nadir counts on those days. If, on toxicity assessment on day 1 of cycle 2, the patient has no residual \>grade 2 toxicity, and all other laboratory parameters are within acceptable limits (see below),at the investigator's discretion the dose can be escalated to 25 mg/m2. 25 mg/m2 is the FDA (Food and Drug Administration)-approved dose for prostate cancer. Neulasta will be given with each dose of cabazitaxel to decrease the risk of febrile neutropenic complication.

Recruitment & Eligibility

Inclusion Criteria

Patients must have histologically confirmed urothelial carcinoma
Patients must have measurable disease
Patients must have been previously treated with a platinum-based regimen, either in the neoadjuvant, adjuvant or first line setting
Patients can have had disease progression while on platinum chemotherapy, or progression within 12 months of completion of therapy
At least 4 weeks must have passed since the last dose of previous chemotherapy
Age > 18 years
ECOG performance status < 2 (Karnofsky > 60%)
Life expectancy of greater than 6 months
Patients must have adequate organ and marrow function as defined below:
absolute neutrophil count > 1,500/mcL
hemoglobin > 9.0 g/dl
platelets > 100,000/mm3
total bilirubin < normal institutional limits (ULN)
AST(SGOT)/ALT(SGPT) < 1.5 X institutional upper limit of normal
creatinine <1.5 x ULN OR creatinine clearance measured > 50 mL/min/1.73 m2for patients with creatinine levels above institutional normal or calculated clearance < 60 by 24 hour urine
Peripheral neuropathy: must be < grade 1
Women of childbearing potential must have a negative pregnancy test, and patients must use adequate contraception during study and for 3 months thereafter
Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

Patients with any component of small cell carcinoma
Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
Patients who are receiving any other investigational agents
Patients with known brain metastases
History of allergic reactions attributed to compounds of similar chemical or biologic composition to taxane chemotherapy
Patients with a history of severe hypersensitivity reaction to Cabazitaxel or other drugs formulated with polysorbate 80
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant and breastfeeding women
HIV-positive patients on combination antiretroviral therapy
Patients who have previously been treated with taxane regimens for bladder cancer or other malignancies
Patients who have had more than one platinum based chemotherapy regimen
Patients whose cancer has progressed more than 12 months following abstinence from platinum based chemotherapy can be included on study at the discretion of the investigator, however should first be considered for platinum re-challenge

Arm && Interventions

Group	Intervention	Description
Cabazitaxel	Neulasta	Cabazitaxel following platinum-based chemotherapy
Cabazitaxel	CT Scan	Cabazitaxel following platinum-based chemotherapy
Cabazitaxel	Blood Draw	Cabazitaxel following platinum-based chemotherapy
Cabazitaxel	Cabazitaxel	Cabazitaxel following platinum-based chemotherapy

Primary Outcome Measures

Name	Time	Method
Overall Response Rate	Every 3 cycles or 63 days	To determine the overall response rate of patients who have disease response while on treatment with Cabazitaxel. CT scan will be used to measure tumor pre-treatment and then every 3 cycles (every 63 days)

Secondary Outcome Measures

Name	Time	Method
Overall Survival	At 12 months	To determine the percentage of patients alive at 12 months from trial entry. Overall survival will be measured from date of randomization to date of death due to any cause.
Progression Free Survival	Every 3 cycles or 63 days	To determine the progression free survival (PFS) of patients with advanced or recurrent urothelial carcinoma who have previously been treated with a platinum based regimen while on treatment with cabazitaxel. Defined as a 20% increase in the largest diameter of the largest lesion by CT scan.
Number of Participants Who Tolerated Cabazitaxel	Up to 30 days after completion of study treatment

Locations (3): National Cancer Institute
🇺🇸
Bethesda, Maryland, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Thomas Jefferson University
🇺🇸
Philadelphia, Pennsylvania, United States