Cisplatin and Gemcitabine Compared With Observation in Treating Patients Who Have Undergone Surgery for Bladder Cancer

Study Description

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Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known if combination chemotherapy is effective in preventing relapse in patients who have undergone radical cystectomy for bladder cancer.

PURPOSE: Phase III trial to compare the effectiveness of cisplatin combined with gemcitabine with that of observation in treating patients with bladder cancer who have undergone surgery to remove the bladder.

Condition or disease	Intervention/treatment	Phase
Bladder Cancer	Drug: cisplatin; Drug: gemcitabine hydrochloride; Procedure: adjuvant therapy	Phase 3

Detailed Description:

OBJECTIVES:

• Compare the overall, cause-specific, and disease-free survival of patients with high-risk muscle-invasive transitional cell carcinoma of the bladder treated with adjuvant cisplatin and gemcitabine vs observation after radical cystectomy.
• Compare the dose intensity and toxicity of two different schedules of cisplatin and gemcitabine in these patients.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center and disease status (T2 [G3 only] or T3-4 [any G], N0-2 vs any T, N1-2, M0). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients are further randomized to 1 of 2 treatment regimens.

  • Regimen A: Patients receive cisplatin IV on day 2 and gemcitabine IV on days 1, 8, and 15.
  • Regimen B: Patients receive cisplatin IV on day 15 and gemcitabine as in regimen A.

Treatment in both regimens repeats every 28 days for 4 courses.

• Arm II: Patients undergo observation followed by cisplatin and gemcitabine as in arm I at relapse.

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

PROJECTED ACCRUAL: A total of 700 patients (350 per treatment arm) will be accrued for this study within 3 years.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	700 participants
Allocation:	Randomized
Primary Purpose:	Treatment
Official Title:	Phase III Study Of Adjuvant Cisplatin-Gemcitabine Vs. Observation After Radical Cystectomy In High-Risk Bladder Cancer
Study Start Date :	September 2001
Estimated Primary Completion Date :	June 2008

Arms and Interventions

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Outcome Measures

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Primary Outcome Measures :

1. Overall survival at 5 years

Secondary Outcome Measures :

1. Disease-free survival at 5 years
2. Local disease-free survival at 5 years
3. Distant disease-free survival at 5 years
4. Toxicity by WHO system grading after each course
5. Quality of life after each course and every 6 months during follow-up
6. Dose intensity at the end of the treatment

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 74 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed transitional cell carcinoma of the bladder

  • T2 (G3 only) or T3-4 (any G), N0-2 or any T, N1-2, M0
  • No secondary localization

• Radical cystectomy (without residual disease) performed within 10 weeks prior to study entry to include:

  • Men: Cystectomy with removal of prostate and seminal vesicles including 1.5 cm of urethra plus pelvic lymphadenectomy (at least 15 negative lymph nodes are recommended to define as N0)
  • Women: Cystectomy with complete removal of the bladder, uterus, ovaries, and anterior walls of the vagina plus pelvic lymphadenectomy

PATIENT CHARACTERISTICS:

Age

• 18 to 74

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,500/mm^3
• Absolute neutrophil count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL

Hepatic

• Bilirubin less than upper normal limit (ULN)
• Gamma-GT less than ULN
• SGOT and SGPT no greater than 2.5 times ULN
• Alkaline phosphatase no greater than 2.5 times ULN

Renal

• Creatinine no greater than1.25 times ULN
• Creatinine clearance at least 60 mL/min

Cardiovascular

• No congestive heart failure
• No angina pectoris
• No cardiac arrhythmia
• No uncontrolled arterial hypertension
• No history of acute myocardial infarction within the past year

Other

• No other serious concurrent illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior systemic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• Palliative radiotherapy allowed at relapse for symptomatic bone metastases

Surgery

• See Disease Characteristics

Contacts and Locations

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  Show 151 Study Locations

Sponsors and Collaborators

Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy

Investigators

Study Chair:	Camillo F. Pollera, MD	Presidio Ospedaliero Belcolle

More Information

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Publications of Results:

Pollera CF, Merendino N, Cianciulli AM, et al.: Preliminary cytogenetic and pharmacogenomic analysis of muscle-invasive transitional-cell carcinoma (TCC) of the bladder in patients (pts) enrolled in the Italian National Research Council (CNR) phase III randomized trial comparing adjuvant cisplatin-gemcitabine (PG) vs observation (OBS) after radical cystectomy. [Abstract] J Clin Oncol 23 (Suppl 16): A-4589, 400s, 2005.

ClinicalTrials.gov Identifier:	NCT00054626 History of Changes
Other Study ID Numbers:	CDR0000258426; ITNRC-CU02.00447ST/97; NCI-V02-1715
First Posted:	February 6, 2003
Last Update Posted:	December 18, 2013
Last Verified:	November 2008

Keywords provided by National Cancer Institute (NCI):

stage II bladder cancer; stage III bladder cancer; stage IV bladder cancer; transitional cell carcinoma of the bladder

Additional relevant MeSH terms:

Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Urinary Bladder Diseases; Urologic Diseases; Gemcitabine; Cisplatin; Antineoplastic Agents	Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs