Gemcitabine, Paclitaxel, Doxorubicin in Metastatic or Unresectable Bladder Cancer With Decreased Kidney Function - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by (Responsible Party):	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00478361

Purpose

RATIONALE: 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 reduce the risk of infection following chemotherapy. This combination of chemotherapy is considered a non kidney toxic combination.

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 with kidney dysfunction.

Condition	Intervention	Phase
Bladder Cancer Renal Insufficiency Carcinoma, Transitional Cell Urethral Cancer Ureteral Cancer TCC Carcinoma, Transitional Cell of Renal Pelvis	Drug: Pegfilgrastim Drug: Doxorubicin Hydrochloride Drug: Gemcitabine Hydrochloride Drug: Paclitaxel	Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/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:

Genetics Home Reference related topics: bladder cancer

MedlinePlus related topics: Bladder Cancer Cancer

Drug Information available for: Hydrochlorothiazide Doxorubicin Doxorubicin hydrochloride Paclitaxel Gemcitabine Filgrastim Gemcitabine hydrochloride Lenograstim Granulocyte colony-stimulating factor Pegfilgrastim

U.S. FDA Resources

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

Primary Outcome Measures:

Objective response rate (complete and partial response) at 6 and 12 weeks [ Time Frame: At 6 and 12 weeks ] [ Designated as safety issue: No ]
Evaluated for response at 6 and 12 weeks, or following completion of 3 and 6 cycles of chemotherapy, respectively. Best response achieved within 6 cycles of starting chemotherapy used to calculate response rate (Complete Response + Partial Response). If study completed with 23 of 40 patients with objective response, then 95% confidence interval will be 0.41 to 0.73.

Secondary Outcome Measures:

Toxicity of gemcitabine paclitaxel and doxorubicin in patients with metastatic TCC and renal insufficiency. [ Time Frame: Every 14 days during chemotherapy ] [ Designated as safety issue: Yes ]
Safety and tolerability of gemcitabine paclitaxel and doxorubicin in patients with metastatic TCC and renal insufficiency measured as toxicity noted in patients receiving chemotherapy graded using NCI Common Terminology Criteria (CTC) version 3 grading system
Median time to progression and survival duration [ Time Frame: Every 6 weeks from registration to end of chemotherapy; then every 3 months for 3 years or until death. ] [ Designated as safety issue: No ]
Time to progression and survival duration calculated from date of registration to progression or death, respectively with participants who receive surgical consolidation of any lesions censored for event-free survival at time of surgery.
Safety and efficacy of pegfilgrastim administered on the day of chemotherapy at 2 week intervals [ Time Frame: Every 14 days during chemotherapy ] [ Designated as safety issue: Yes ]
Toxicity events tabulated and described with frequency of neutropenic fever or treatment delay because of neutropenia observed as a measure of the safety and efficacy of pegfilgrastim administered on the same day as chemotherapy.

Estimated Enrollment:	40
Study Start Date:	April 2007
Estimated Study Completion Date:	December 2015
Estimated Primary Completion Date:	December 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Gemcitabine + Paclitaxel + Doxorubicin Gemcitabine 900 mg/m^2 by vein (IV), Paclitaxel 135 mg/m^2 IV, and Doxorubicin 40 mg/m^2 IV all on Day 1 of 14 day cycle	Drug: Pegfilgrastim 6 mg subcutaneously on Day 1 or 2 of each 14 day course, after chemotherapy. Other Names: Neulasta PEG-G-CSF G-CSF (PEG Conjugate) Granulocyte Colony Stimulating Factor (PEG Conjugate) NSC-725961 Pegylated G-CSF SD/01 Drug: Doxorubicin Hydrochloride 40 mg/m^2 by vein (IV) over 20 min on Day 1 of 14 day cycle Other Names: Adriamycin Rubex Adri Doxorubicin Hydroxydaunomycin Hydrochloride Hydroxyldaunorubicin Hydrochloride Drug: Gemcitabine Hydrochloride 900 mg/m^2 IV over 90 min on Day 1 of 14 day cycle Other Names: Gemcitabine Gemzar ® dFdC dFdCyd Difluorodeoxycytidine Hydrochlorothiazide LY-188011 Drug: Paclitaxel 135 mg/m^2 IV over 1 hour on Day 1 of 14 day cycle Other Name: Taxol ®

Arms

Assigned Interventions

Experimental: Gemcitabine + Paclitaxel + Doxorubicin

Gemcitabine 900 mg/m^2 by vein (IV), Paclitaxel 135 mg/m^2 IV, and Doxorubicin 40 mg/m^2 IV all on Day 1 of 14 day cycle

Drug: Pegfilgrastim

6 mg subcutaneously on Day 1 or 2 of each 14 day course, after chemotherapy.

Other Names:

Neulasta
PEG-G-CSF
G-CSF (PEG Conjugate)
Granulocyte Colony Stimulating Factor (PEG Conjugate)
NSC-725961
Pegylated G-CSF
SD/01

Drug: Doxorubicin Hydrochloride

40 mg/m^2 by vein (IV) over 20 min on Day 1 of 14 day cycle

Other Names:

Adriamycin
Rubex
Adri
Doxorubicin
Hydroxydaunomycin Hydrochloride
Hydroxyldaunorubicin Hydrochloride

Drug: Gemcitabine Hydrochloride

900 mg/m^2 IV over 90 min on Day 1 of 14 day cycle

Other Names:

Gemcitabine
Gemzar ®
dFdC
dFdCyd
Difluorodeoxycytidine Hydrochlorothiazide
LY-188011

Drug: Paclitaxel

135 mg/m^2 IV over 1 hour on Day 1 of 14 day cycle

Other Name: Taxol ®

Detailed Description:

OBJECTIVES:

Primary

*To assess efficacy, measured as response rate, of gemcitabine, paclitaxel, and doxorubicin in metastatic transitional cell carcinoma (TCC).

Secondary

To assess the safety and tolerability of gemcitabine, paclitaxel, and doxorubicin in patients with metastatic TCC and renal insufficiency.
To measure the median time to progression and median survival duration in patients with metastatic TCC and renal insufficiency after treatment with gemcitabine, paclitaxel, and doxorubicin.
To assess the safety and efficacy of pegfilgrastim administered on the day of chemotherapy at two-week intervals.

This is a multicenter study.

Patients receive doxorubicin intravenous (IV) over 20 minutes, paclitaxel IV over 60 minutes, gemcitabine IV over 90 minutes, and pegfilgrastim subcutaneously on day 1 or 2. 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.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients must have histologically or cytologically confirmed metastatic or unresectable TCC of bladder, urethra or upper urinary tract. Mixed TCC and variant histologies (small cell, squamous, adenocarcinoma, sarcoma) are permitted if present in < 50% of the biopsy specimen.
No prior systemic chemotherapy. Any prior intravesicular chemotherapy is allowed.
Measurable disease, which may include radiographic detection of metastases in lymph nodes (>/= 1.5 cm), liver or lung (>/= 1.0 cm), or pelvic mass palpable on examination under anesthesia.
Creatinine clearance < 60 ml/min (calculated or measured). Cockroft and Gault Equation: Creatinine clearance = (140 - age [years])(body weight [kg]) / (72) (serum creatinine (mg/dl)) (Multiply by 0.8 for females; use only non-IDMS creatinine values for Cockroft-Gault calculations.)
Zubrod performance status 2 or better
Left ventricular ejection fraction (LVEF)> 40%, or normal Electrocardiogram (EKG) and no history of cardiac disease
Patients must have adequate bone marrow function defined as an absolute peripheral granulocyte count (ANC) of > 1,500/mm^3 and platelet count of > 100,000/mm^3.
Adequate hepatic function defined with a total bilirubin of </= 2.0 mg/dl and aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) </= 2* the upper limits of normal
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.
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.

Exclusion Criteria:

Patients with known or clinical suspicion of brain metastases.
Renal insufficiency that requires hemodialysis.
Renal insufficiency that is reversible in patients with tumor confined to the primary site (i.e., that is potentially resectable with neoadjuvant chemotherapy).
Prior systemic gemcitabine, paclitaxel, doxorubicin, or any systemic chemotherapy for metastatic transitional cell carcinoma. Any prior intravesicular chemotherapy is allowed. Patients with prior systemic chemotherapy are eligible only if no gemcitabine, paclitaxel, doxorubicin, or mitoxantrone was given, and the treatment was completed at least 3 years before protocol entry in the case of second malignancies, or 1 year before protocol entry in the case of adjuvant or neoadjuvant chemotherapy for locally advanced urothelial carcinoma.
Patients with severe or uncontrolled intercurrent infection.
Patients with The New York Heart Association (NYHA) Class III/IV congestive heart failure, unstable angina, or history of myocardial infarction within the last 6 months.
Peripheral neuropathy, grade 2 or worse.
Uncontrolled severe hypertension, persistently uncontrolled diabetes mellitus, chronic liver disease or HIV infection.
Second malignancies (excluding non-melanoma skin cancer) unless disease-free for 3 years.
Overt psychosis, mental disability, or otherwise incompetent to give informed consent.
Women who are pregnant, likely to become pregnant, or lactating are excluded.
Patients known to have sickle cell disease.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00478361

Locations

United States, Arkansas
Saint Edward Mercy Medical Center
Fort Smith, Arkansas, United States, 72917
United States, Louisiana
Christus St. Frances Cabrini Center for Cancer Care
Alexandria, Louisiana, United States, 71301
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009

Sponsors and Collaborators

M.D. Anderson Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Lance C. Pagliaro, MD

M.D. Anderson Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

UT MD Anderson Cancer Center website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00478361 History of Changes
Obsolete Identifiers:	NCT00477438
Other Study ID Numbers:	MDA 2005-0839, P30CA016672, 7341, CDR0000544831
Study First Received:	May 23, 2007
Last Updated:	November 11, 2011
Health Authority:	United States: Federal Government

Keywords provided by M.D. Anderson Cancer Center:

renal insufficiency
metastatic urothelial cancer
unresectable urothelial cancer
metastatic transitional cell cancer
metastatic transitional cancer of the renal pelvis
urethral cancer associated with invasive bladder cancer
unresectable urethral cancer

recurrent bladder cancer
stage IV bladder cancer
transitional cell carcinoma of the bladder
recurrent urethral cancer
metastatic cancer of the ureter
stage III bladder cancer
metastatic or unresectable TCC

Additional relevant MeSH terms:

Urinary Bladder Neoplasms
Carcinoma
Carcinoma, Transitional Cell
Ureteral Neoplasms
Urethral Neoplasms
Renal Insufficiency
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Ureteral Diseases

Urethral Diseases
Kidney Diseases
Doxorubicin
Gemcitabine
Paclitaxel
Hydrochlorothiazide
Lenograstim
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors

ClinicalTrials.gov processed this record on February 12, 2012