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

A Phase II Study of Gemcitabine, Paclitaxel, and Doxorubicin, With Pegfilgrastim for the Treatment of Patients With Metastatic Transitional Cell Carcinoma and Renal Insufficiency

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Distal Urethral Cancer; Proximal Urethral Cancer; Recurrent Urethral Cancer; Urethral Cancer Associated With Invasive Bladder Cancer
• Intervention / Treatment: Drug: Gemcitabine hydrochloride; Drug: Paclitaxel; Drug: Doxorubicin hydrochloride; Drug: Pegfilgrastim

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Springfield, Missouri, United States, 65802
      • Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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: Gemzar; gemcitabine; dFdC; difluorodeoxycytidine hydrochloride; Drug: Paclitaxel; 135 mg/m^2 IV over 1 hour; Other Names: Taxol; Anzatax; Asotax; TAX; Drug: Doxorubicin hydrochloride; Doxorubicin 40 mg/m^2 IV over 20 minutes; Other Names: ADM; Adriamycin PFS; Adriamycin RDF; ADR; Adria; Drug: Pegfilgrastim; Subcutaneously injection on day 1.; Other Names: Filgrastim SD-01; Neulasta; SD-01 sustained duration G-CSF; GCSF-SD01

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	The percentage of participants with either Complete Response (CR) or Partial Response (PR) in their disease burden based upon the rules of the Response Evaluation Criteria in Solid Tumors (RECIST). A participant with of all of the lesions disappearing is a CR. A participant with at least a 30 percent decrease in the measured lesions is a PR.	Up to 12 weeks, or following completion 6 cycles of chemotherapy, respectively; the best response achieved within 6 cycles of starting chemotherapy used to calculate response rate.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) of Participants With a Continuous Complete Response, Partial Response and Stable Disease	The overall survival was determined by grouping participants based upon their response based on RECIST. The groups are Complete Response(CR): All the cancerous lesion disappear, Partial Response (PR): All the measured lesions decrease by at least 30 percent, and Stable Disease(SD): No significant change in the disease burden. OS of complete response or partial response participants were compared to the reference group of stable disease participants in a Hazard Ratio(HR). If HR is greater than 1, the experimental group has a better outcome than the reference group. If HR is less than 1, the reference group has the better outcome.	Registration Date of each participant for up to three years or death whichever came first
Safety and Efficacy of Same-day Pegfilgrastim	Determined the number of participants who had either a fever due to abnormally low level of neutrophils, a type of white blood cell, on the day of study drug treatment, or the participants who had the study drug treatment delayed due to an abnormally low level of neutrophils.	Up to 3 years

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Lance Pagliaro, MD, BA, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• University of Texas MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: May 23, 2007
• First Submitted That Met QC Criteria: May 23, 2007
• First Posted (Estimate): May 24, 2007

Study Record Updates

• Last Update Posted (Actual): October 9, 2020
• Last Update Submitted That Met QC Criteria: September 17, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Disease Attributes; Ureteral Diseases; Urethral Diseases; Kidney Neoplasms; Carcinoma; Recurrence; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Ureteral Neoplasms; Urethral Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Gemcitabine; Paclitaxel; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: 2005-0839; NCI-2009-00154 (Registry Identifier: CTRP (Clinical Trials Reporting System)); CDR0000544831; 2U10CA045809-17 (U.S. NIH Grant/Contract)