Cisplatin Plus Gemcitabine With or Without Paclitaxel in Treating Patients With Stage IV Urinary Tract Cancer

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.

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

Conditions

Bladder CancerTransitional Cell Cancer of the Renal Pelvis and UreterUrethral Cancer

Study Type

Interventional

Study Design

Treatment, Randomized, Open Label, Active Control

Further Details

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.

Study Start

May 2001

Eligibility & Criteria

• Ages Eligible for Study: 18 Years and above
• Genders Eligible for Study: Both

Inclusion Criteria:

• 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
• Aged 18 and over
• Performance status: WHO 0-1
• Life expectancy: At least 12 weeks
• Hematopoietic:
  • WBC at least 3,000/mm³
  • Platelet count at least 100,000/mm³
  • 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
• 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 and at least 4 weeks since prior local intravesical chemotherapy
• Radiotherapy: No more than 1 prior course of radiotherapy and at least 4 weeks since prior radiotherapy and recovered
• Surgery: Prior urological procedures to relieve urinary tract obstruction and improve renal function allowed (e.g., ureteral stent or percutaneous nephrostomy)

Total Enrolment

610

Contact Details

• Fremantle Hospital, Fremantle, Western Australia, 6160, Australia

More information from The National Cancer InstituteResults published in:

• Bellmunt J, von der Maase H, Mead GM, et al.: Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine (PCG) and gemcitabine/cisplatin (GC) in patients with locally advanced (LA) or metastatic (M) urothelial cancer without prior systemic therapy: EORTC30987/Intergroup study. [Abstract] J Clin Oncol 25 (Suppl 18): A-LBA5030, 242s, 2007.