Clinical trial NCT00478361: 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
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-05-24
Enrollment: 40
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Objective Response Rate
timeFrame: 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 outcomes:
measure: Overall Survival (OS) of Participants With a Continuous Complete Response, Partial Response and Stable Disease
timeFrame: Registration Date of each participant for up to three years or death whichever came first
measure: Safety and Efficacy of Same-day Pegfilgrastim
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Springfield
country: United States
facility: Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield
state: Missouri
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Lance Pagliaro, MD, BA
role: PRINCIPAL_INVESTIGATOR
References: