Official Title: “Randomized Phase III Study Comparing Paclitaxel/Cisplatin/Gemcitabine and Cisplatin/Gemcitabine in Patients With Metastatic or Locally Advanced Urothelial Cancer Without Prior Systemic Therapy”

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which combination chemotherapy regimen is more effective for urinary tract cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of cisplatin plus gemcitabine with or without paclitaxel in treating patients who have stage IV urinary tract cancer.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control

OBJECTIVES: - Compare the duration of survival of patients with stage IV transitional cell carcinoma of the urothelium treated with cisplatin and gemcitabine with or without paclitaxel. - Compare the duration of progression-free survival, response rates, and duration of response in patients treated with these regimens. - Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center, WHO performance status (0 vs 1), and presence of metastatic disease (yes vs no). Patients are randomized to one of two treatment arms. - Arm I: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 and cisplatin IV over 1 hour on day 1 or 2. Treatment repeats every 28 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity. - Arm II: Patients receive paclitaxel IV over 1 hour on days 1 and 8 followed by cisplatin IV over 1 hour on day 1 and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for at least 3 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 610 patients (305 per treatment arm) will be accrued for this study within 3.04 years.

Intervention(s) in this Clinical Trial

• Drug: cisplatin
• Drug: gemcitabine hydrochloride
• Drug: paclitaxel

DISEASE CHARACTERISTICS:

• Histologically confirmed stage IV transitional cell carcinoma of the urothelium (pure or mixed) including bladder, urethra, ureter, and renal pelvis
• T4b, any N OR any T, N2-3 OR M1
• Ineligible for surgery or radiotherapy with curative intent
• Measurable or evaluable disease
• No known CNS metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• WHO 0-1

Life expectancy:

• At least 12 weeks

Hematopoietic:

• WBC at least 3,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL

Hepatic:

• Bilirubin less than 1.25 times normal
• AST or ALT less than 2.5 times normal

Renal:

• Glomerular filtration rate at least 60 mL/min
• Calcium normal or clinically insignificant

Cardiovascular:

• No clinically significant cardiac arrhythmia
• No congestive heart failure
• No complete bundle branch block
• No New York Heart Association class III or IV heart disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study participation
• No psychological, familial, sociological, or geographical condition that would preclude study compliance
• No grade 3 or 4 infection without neutropenia
• No other serious concurrent systemic disorder that would preclude study therapy
• No mental disorder that would preclude study compliance
• No grade II or greater neuropathy
• No other prior or concurrent malignancy except appropriately treated carcinoma in situ of the cervix, basal cell carcinoma of the skin, or incidental prostate cancer (T1, Gleason score no greater than 6, and PSA less than 0.5 ng/mL)

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior investigational biologic agents (e.g., antiangiogenic products, signal transduction pathway inhibitors, immunomodulators, or monoclonal antibody therapy)
• At least 4 weeks since prior immunotherapy

Chemotherapy:

• No prior systemic chemotherapy
• At least 4 weeks since prior local intravesical chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• No more than 1 prior course of radiotherapy
• At least 4 weeks since prior radiotherapy and recovered

Surgery:

• See Disease Characteristics
• Prior urological procedures to relieve urinary tract obstruction and improve renal function allowed (e.g., ureteral stent or percutaneous nephrostomy)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: European Organization for Research and Treatment of Cancer

Overall Clinical Trial Officials and Contacts

Joaquim Bellmunt, MD, PhD Study Chair Vall d'Hebron University Hospital  

Information obtained from ClinicalTrials.gov on January 06, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00022191

Study ID Number: CDR0000068793

ClinicalTrials.gov Identifier: NCT00022191

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database