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

Primary Purpose

Urothelial Carcinoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cabazitaxel
Neulasta
CT Scan
Blood Draw
Sponsored by
Sidney Kimmel Cancer Center at Thomas Jefferson University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Urothelial Carcinoma focused on measuring Urothelial carcinoma, Urothelial cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • National Cancer Institute
  • University of Pennsylvania
  • Thomas Jefferson University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cabazitaxel

Arm Description

Cabazitaxel following platinum-based chemotherapy

Outcomes

Primary Outcome Measures

Overall Response Rate
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

Overall Survival
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
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

Full Information

First Posted
August 31, 2011
Last Updated
October 18, 2017
Sponsor
Sidney Kimmel Cancer Center at Thomas Jefferson University
Collaborators
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT01437488
Brief Title
Cabazitaxel in Patients With Urothelial Carcinoma Who Have Disease Progression Following Platinum-Based Chemotherapy
Official Title
A Phase II Study of Cabazitaxel in Patients With Urothelial Carcinoma Who Have Disease Progression Following Platinum-Based Chemotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
February 16, 2012 (Actual)
Primary Completion Date
August 4, 2014 (Actual)
Study Completion Date
March 30, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Cancer Center at Thomas Jefferson University
Collaborators
Sanofi

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urothelial Carcinoma
Keywords
Urothelial carcinoma, Urothelial cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cabazitaxel
Arm Type
Experimental
Arm Description
Cabazitaxel following platinum-based chemotherapy
Intervention Type
Drug
Intervention Name(s)
Cabazitaxel
Other Intervention Name(s)
XRP-6258, Jevtana
Intervention Description
Cycle 1: 20 mg/m2 in 250cc NS via IV on Day 1 every 21 days Following cycles: 20 mg/m2 or escalated to 25 mg/m2 or reduced by 5 mg/m2 in 250cc NS via IV on Day 1 every 21 days at investigator's discretion Treatment continues until disease progression, intercurrent illness preventing further treatment, unacceptable adverse event(s), patient withdraws from the study, or changes in the patient's condition which render further treatment unacceptable in the judgment of the investigator
Intervention Type
Drug
Intervention Name(s)
Neulasta
Other Intervention Name(s)
Pegfilgrastim
Intervention Description
6 mg via SQ on Day 2 (24-48 hours post-cabazitaxel) every 21 days
Intervention Type
Procedure
Intervention Name(s)
CT Scan
Other Intervention Name(s)
X-ray computed tomography
Intervention Description
CT scan of chest, abdomen, and pelvis to assess disease following every 3rd cycle of treatment (approximately every 9 weeks)
Intervention Type
Biological
Intervention Name(s)
Blood Draw
Other Intervention Name(s)
Venipuncture
Intervention Description
Approximately 2 tablespoons of blood will be taken to test complete blood count, glucose, hematology, electrolytes, liver function, creatinine clearance, and a chemistry profile. This week be done weekly during the first cycle of treatment
Primary Outcome Measure Information:
Title
Overall Response Rate
Description
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)
Time Frame
Every 3 cycles or 63 days
Secondary Outcome Measure Information:
Title
Overall Survival
Description
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.
Time Frame
At 12 months
Title
Progression Free Survival
Description
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.
Time Frame
Every 3 cycles or 63 days
Title
Number of Participants Who Tolerated Cabazitaxel
Time Frame
Up to 30 days after completion of study treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean Hoffman-Censits, MD
Organizational Affiliation
Thomas Jefferson University
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Cancer Institute
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.jeffersonhospital.org/
Description
Thomas Jefferson University Hospital
URL
http://ccr.cancer.gov/
Description
Center for Cancer Research, National Cancer Institute
URL
http://penncancer.org/
Description
Abramson Cancer Center of the University of Pennsylvania

Learn more about this trial

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

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