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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT01437488
First received: August 31, 2011
Last updated: January 29, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Urothelial Carcinoma
Drug: Cabazitaxel
Drug: Neulasta
Procedure: CT Scan
Biological: Blood Draw
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Cabazitaxel in Patients With Urothelial Carcinoma Who Have Disease Progression Following Platinum-Based Chemotherapy

Resource links provided by NLM:


Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:
  • Overall Response Rate [ Time Frame: Pre-treatment and then every 3 cycles or 63 days ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: At 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Every 3 cycles or 63 days ] [ Designated as safety issue: No ]
    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.

  • Safety and Tolerability of Cabazitaxel [ Time Frame: Every 1 cycle or 21 days ] [ Designated as safety issue: Yes ]
    Determined through dose modifications according to patient's toxicity levels. For example, if after Cycle 1 the patient shows no residual toxicity, the dose level will be increased.


Estimated Enrollment: 33
Study Start Date: February 2012
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cabazitaxel
Cabazitaxel following platinum-based chemotherapy
Drug: Cabazitaxel
  • 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
Other Names:
  • Cabazitaxel
  • XRP-6258
  • Jevtana
Drug: Neulasta
6 mg via SQ on Day 2 (24-48 hours post-cabazitaxel) every 21 days
Other Name: Pegfilgrastim
Procedure: CT Scan
CT scan of chest, abdomen, and pelvis to assess disease following every 3rd cycle of treatment (approximately every 9 weeks)
Other Names:
  • CT scan
  • X-ray computed tomography
Biological: Blood Draw
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
Other Names:
  • Blood draw
  • Venipuncture

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01437488

Locations
United States, Maryland
National Cancer Institute
Bethesda, Maryland, United States, 20892
United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Thomas Jefferson University
Sanofi
Investigators
Principal Investigator: Jean Hoffman-Censits, MD Thomas Jefferson University
  More Information

Additional Information:
No publications provided

Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT01437488     History of Changes
Other Study ID Numbers: 11D.392, 2011-52
Study First Received: August 31, 2011
Last Updated: January 29, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Thomas Jefferson University:
Urothelial carcinoma
Urothelial cancer

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Transitional Cell
Disease Progression
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Disease Attributes
Pathologic Processes

ClinicalTrials.gov processed this record on August 21, 2014