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

NCT ID: NCT00478361

Last Updated: 2020-10-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2015-06-30

Brief Summary

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.

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Gemcitabine hydrochloride

Intervention Type: DRUG

Gemcitabine 900 mg/m\^2 IV over 90 minutes repeat every 14 days.

Paclitaxel

Intervention Type: DRUG

135 mg/m\^2 IV over 1 hour

Doxorubicin hydrochloride

Intervention Type: DRUG

Doxorubicin 40 mg/m\^2 IV over 20 minutes

Pegfilgrastim

Intervention Type: DRUG

Subcutaneously injection on day 1.

Interventions

Gemcitabine hydrochloride

Gemcitabine 900 mg/m\^2 IV over 90 minutes repeat every 14 days.

Intervention Type: DRUG

Paclitaxel

135 mg/m\^2 IV over 1 hour

Intervention Type: DRUG

Doxorubicin hydrochloride

Doxorubicin 40 mg/m\^2 IV over 20 minutes

Intervention Type: DRUG

Pegfilgrastim

Subcutaneously injection on day 1.

Intervention Type: DRUG

Other Intervention Names

dFdC; difluorodeoxycytidine hydrochloride; gemcitabine; Gemzar; Anzatax; Asotax; TAX; Taxol; ADM; ADR; Adria; Adriamycin PFS; Adriamycin RDF; Filgrastim SD-01; GCSF-SD01; Neulasta; SD-01 sustained duration G-CSF

Eligibility 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
• Aminotransferases (AST and ALT) =< 2 times upper limit of normal
• Left ventricular ejection fraction (LVEF) > 40% OR normal electrocardiogram (EKG or ECG) 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).

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lance Pagliaro, MD, BA

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield

Springfield, Missouri, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Related Links

http://www.mdanderson.org

University of Texas MD Anderson Cancer Center Website

Other Identifiers

NCI-2009-00154

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000544831

Identifier Type: -

Identifier Source: secondary_id

2U10CA045809-17

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2005-0839

Identifier Type: -

Identifier Source: org_study_id

NCT00477438

Identifier Type: -

Identifier Source: nct_alias