Gemcitabine, Paclitaxel, Doxorubicin in Metastatic or Unresectable Bladder Cancer With Decreased Kidney Function

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00478361
First received: May 23, 2007
Last updated: September 3, 2014
Last verified: September 2014
  Purpose

This phase II trial is studying how well giving gemcitabine, paclitaxel, and doxorubicin together with pegfilgrastim works in treating patients with metastatic or unresectable bladder cancer or urinary tract cancer and kidney dysfunction. Drugs used in chemotherapy, such as gemcitabine, paclitaxel, and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Colony stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving combination chemotherapy together with pegfilgrastim may kill more tumor cells. Chemotherapy drugs may have different effects in patients who have changes in their kidney function.


Condition Intervention Phase
Distal Urethral Cancer
Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter
Proximal Urethral Cancer
Recurrent Bladder Cancer
Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter
Recurrent Urethral Cancer
Regional Transitional Cell Cancer of the Renal Pelvis and Ureter
Stage III Bladder Cancer
Stage IV Bladder Cancer
Transitional Cell Carcinoma of the Bladder
Urethral Cancer Associated With Invasive Bladder Cancer
Drug: Gemcitabine hydrochloride
Drug: Paclitaxel
Drug: Doxorubicin hydrochloride
Drug: Pegfilgrastim
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Gemcitabine, Paclitaxel, and Doxorubicin, With Pegfilgrastim for the Treatment of Patients With Metastatic Transitional Cell Carcinoma and Renal Insufficiency

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Overall response rate (complete and partial response) [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    Overall response defined as participants with Complete or Partial Response using Response Evaluation Criteria in Solid Tumors (RECIST): Complete Response: Disappearance of all target lesions. Partial Response: At least 30% decrease in sum of longest diameter of target lesions, reference baseline sum longest diameter. Progressive Disease: At least a 20% increase in sum of longest diameter of target lesions, reference smallest sum longest diameter recorded since treatment started or appearance of 1 or > new lesions. Stable Disease: Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, reference smallest sum longest diameter since treatment started.

  • Time to progression [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Time measured in months from the date of protocol registration to disease progression, assessed up to 3 years

  • Survival duration [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Time measured from the date of protocol registration to death, assessed up to 3 years

  • Frequency of neutropenic fever or treatment delay because of neutropenia [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Safety and efficacy of pegfilgrastim administered on the day of chemotherapy measured by the frequency of neutropenic fever or treatment delay because of neutropenia


Estimated Enrollment: 40
Study Start Date: April 2007
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gemcitabine, Paclitaxel and Doxorubicin
Paclitaxel 135 mg/m^2 intravenous (IV) over 1 hour; Gemcitabine 900 mg/m^2 IV over 90 min; Doxorubicin 40 mg/m^2 IV over 20 min; treatment may repeat every 2 weeks for up to nine courses. Injection of Pegfilgrastim on day 1.
Drug: Gemcitabine hydrochloride
Gemcitabine 900 mg/m^2 IV over 90 minutes repeat every 14 days.
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Drug: Paclitaxel
135 mg/m^2 IV over 1 hour
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: Doxorubicin hydrochloride
Doxorubicin 40 mg/m^2 IV over 20 minutes
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: Pegfilgrastim
Subcutaneously injection on day 1.
Other Names:
  • Filgrastim SD-01
  • GCSF-SD01
  • Neulasta
  • SD-01 sustained duration G-CSF

Detailed Description:

PRIMARY OBJECTIVES:

I. Assess the efficacy of gemcitabine hydrochloride, paclitaxel, doxorubicin hydrochloride, and pegfilgrastim, in terms of response rate, in patients with metastatic or unresectable transitional cell carcinoma of the bladder or urinary tract and renal insufficiency.

SECONDARY OBJECTIVES:

I. Assess the safety and tolerability of this regimen in these patients. II. Determine the median time to progression in patients treated with this regimen.

III. Determine the median survival duration in patients treated with this regimen.

IV. Assess the safety and efficacy of pegfilgrastim in these patients.

OUTLINE: This is a multicenter study.

Patients receive doxorubicin hydrochloride intravenous (IV) over 20 minutes, paclitaxel IV over 60 minutes, gemcitabine hydrochloride IV over 90 minutes, and pegfilgrastim subcutaneously on day 1. Treatment repeats every 14 days for up to 9 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 3 years.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed transitional cell carcinoma (TCC) of the bladder, urethra, or upper urinary tract
  • Mixed TCC and variant histologies (i.e., small cell, squamous cell, adenocarcinoma, or sarcoma) allowed if present in < 50% of the biopsy specimen
  • Patients must sign an informed consent indicating that they are aware of the investigational nature of this study, in keeping with the policies of the institution.
  • Measurable disease: may include radiographic detection of metastases in lymph nodes (>= 1.5 cm) or liver or lung (>= 1.0 cm) OR pelvic mass palpable on examination under anesthesia
  • Creatinine clearance < 60 mL/min; no renal insufficiency that requires hemodialysis; no renal insufficiency that is reversible in patients with tumor confined to the primary site (i.e., that is potentially resectable with neoadjuvant chemotherapy)
  • Zubrod performance status 0-2
  • Platelet count > 100,000/mm^3
  • Absolute granulocyte count > 1,500/mm^3
  • Bilirubin =< 2.0 mg/dL
  • AST and ALT =< 2 times upper limit of normal
  • LVEF > 40% OR normal EKG and no history of cardiac disease
  • All patients must be evaluated in the Department of Genitourinary Medical Oncology at M. D. Anderson Cancer Center or participating CCOP center prior to signing informed consent.
  • No prior systemic chemotherapy including, adjuvant or neoadjuvant therapy
  • Prior intravesicular chemotherapy allowed

Exclusion Criteria:

  • No brain metastases
  • Not pregnant or nursing
  • No severe or uncontrolled infection
  • No New York Heart Association class III-IV congestive heart failure, unstable angina, or history of myocardial infarction within the past 6 months
  • No peripheral neuropathy >= grade 2
  • No persistently uncontrolled diabetes mellitus
  • No chronic liver disease
  • No HIV positivity
  • No other malignancy except nonmelanoma skin cancer unless disease-free for the past 3 years
  • No overt psychosis, mental disability, or other condition that would preclude giving informed consent
  • No known sickle cell disease
  • No uncontrolled severe hypertension
  • Renal insufficiency that requires hemodialysis or renal insufficiency that is reversible in patients with tumor confined to the primary site (i.e., that is potentially resectable with neoadjuvant chemotherapy).
  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: NCT00478361

Locations
United States, Missouri
Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield
Springfield, Missouri, United States, 65802
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Lance Pagliaro, MD, BA M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00478361     History of Changes
Obsolete Identifiers: NCT00477438
Other Study ID Numbers: 2005-0839, NCI-2009-00154, CDR0000544831, 2 U10 CA45809-17
Study First Received: May 23, 2007
Last Updated: September 3, 2014
Health Authority: United States: Food and Drug Administration
United States: Federal Government

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Urethral Neoplasms
Kidney Neoplasms
Ureteral Neoplasms
Carcinoma
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urethral Diseases
Kidney Diseases
Ureteral Diseases
Paclitaxel
Gemcitabine
Liposomal doxorubicin
Doxorubicin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic

ClinicalTrials.gov processed this record on September 22, 2014