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

Primary Purpose

Distal Urethral Cancer, Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter, Proximal Urethral Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Gemcitabine hydrochloride
Paclitaxel
Doxorubicin hydrochloride
Pegfilgrastim
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Distal Urethral Cancer

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield
  • University of Texas MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Gemcitabine, Paclitaxel and Doxorubicin

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
May 23, 2007
Last Updated
September 17, 2020
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00478361
Brief Title
Gemcitabine, Paclitaxel, Doxorubicin in Metastatic or Unresectable Bladder Cancer With Decreased Kidney Function
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
April 2007 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Gemcitabine, Paclitaxel and Doxorubicin
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine hydrochloride
Other Intervention Name(s)
dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar
Intervention Description
Gemcitabine 900 mg/m^2 IV over 90 minutes repeat every 14 days.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Anzatax, Asotax, TAX, Taxol
Intervention Description
135 mg/m^2 IV over 1 hour
Intervention Type
Drug
Intervention Name(s)
Doxorubicin hydrochloride
Other Intervention Name(s)
ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF
Intervention Description
Doxorubicin 40 mg/m^2 IV over 20 minutes
Intervention Type
Drug
Intervention Name(s)
Pegfilgrastim
Other Intervention Name(s)
Filgrastim SD-01, GCSF-SD01, Neulasta, SD-01 sustained duration G-CSF
Intervention Description
Subcutaneously injection on day 1.
Primary Outcome Measure Information:
Title
Objective Response Rate
Description
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.
Time Frame
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 Measure Information:
Title
Overall Survival (OS) of Participants With a Continuous Complete Response, Partial Response and Stable Disease
Description
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.
Time Frame
Registration Date of each participant for up to three years or death whichever came first
Title
Safety and Efficacy of Same-day Pegfilgrastim
Description
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.
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lance Pagliaro, MD, BA
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield
City
Springfield
State/Province
Missouri
ZIP/Postal Code
65802
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
University of Texas MD Anderson Cancer Center Website

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

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