Combination Chemotherapy in Treating Patients With Transitional Cell Cancer of the Urothelium - Full Text View

Sponsor:	European Organization for Research and Treatment of Cancer
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00014274

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which combination chemotherapy regimen is most effective for transitional cell cancer of the urothelium.

PURPOSE: Randomized phase II/III trial to compare different combination chemotherapy regimens in treating patients who have transitional cell cancer of the urothelium.

Condition	Intervention	Phase
Bladder Cancer Transitional Cell Cancer of the Renal Pelvis and Ureter Urethral Cancer	Drug: carboplatin Drug: gemcitabine hydrochloride Drug: methotrexate Drug: vinblastine	Phase II Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	Randomized Phase II/III Study Assessing Gemcitabine/Carboplatin And Methotrexate/Carboplatin/Vinblastine In Previously Untreated Patients With Advanced Urothelial Cancer Ineligible For Cisplatin Based Chemotherapy

Resource links provided by NLM:

Genetics Home Reference related topics: bladder cancer

MedlinePlus related topics: Bladder Cancer Cancer

Drug Information available for: Methotrexate Carboplatin Gemcitabine Gemcitabine hydrochloride Vinblastine sulfate Vinblastine

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Duration of survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response as assessed by RECIST criteria [ Designated as safety issue: No ]
Toxicity as assessed by CTC v2 [ Designated as safety issue: Yes ]

Estimated Enrollment:	225
Study Start Date:	January 2001
Estimated Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Compare the antitumor activity of gemcitabine and carboplatin vs methotrexate, carboplatin, and vinblastine in patients with transitional cell cancer of the urothelium who are ineligible for cisplatin-based chemotherapy.
Compare the toxicity and acute and intermediate (1-2 years) side effects of these regimens in these patients.
Compare the complete response rates, progression-free survival, and overall survival of patients treated with these regimens.
Compare the symptoms and quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms.

Arm I: Patients receive methotrexate* IV and vinblastine IV on days 1, 15, and 22 and carboplatin IV over 1 hour on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Arm II: Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and carboplatin IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

NOTE: * Methotrexate is omitted for patients with pleural effusion or ascites until complete resolution and for patients with a glomerular filtration rate less than 30 mL/min or creatinine greater than 2 mg/dL

Patients in either arm who achieve a complete response (CR) receive 2 additional courses of chemotherapy beyond CR.

Quality of life is assessed at baseline, after every 2 courses of chemotherapy, and within 6 weeks of completion of therapy.

Patients are followed within 6 weeks, every 3 months for 1 year, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 156 patients (78 per treatment arm) will be accrued for the phase II portion of this study. A total of 225 patients will be accrued for the phase II + III portions of this study within 5 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed transitional cell cancer of the urothelium, including the renal pelvis, ureters, urinary bladder, and urethra, meeting 1 of the following criteria:
- Unresected positive lymph node
- Distant metastases (M1, stage IV)
- Unresectable primary bladder cancer (T3-4)
Measurable disease
Ineligible for cisplatin-based chemotherapy and presenting with the following:
- WHO performance status 2 AND/OR
- Glomerular filtration rate greater than 30 mL/min but less than 60 mL/min
No brain metastases or other CNS lesions

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

See Disease Characteristics

Life expectancy:

Not specified

Hematopoietic:

WBC at least 4,000/mm^3
Platelet count at least 125,000/mm^3

Hepatic:

Bilirubin no greater than 1.25 times normal
AST/ALT no greater than 3 times normal (5 times normal if liver metastases are present)

Renal:

See Disease Characteristics
Calcium normal

Other:

Not pregnant or nursing
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 participation
No other prior or concurrent malignancy except cured basal cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No prior systemic biologic therapy

Chemotherapy:

See Disease Characteristics
No prior systemic cytotoxic therapy (including adjuvant and neoadjuvant chemotherapy)

Endocrine therapy:

Not specified

Radiotherapy:

At least 3 months since prior radiotherapy
Prior radiotherapy to study lesions allowed if there is evidence of disease progression

Surgery:

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00014274

Hide Study Locations

Locations

Austria
Ludwig Boltzmann Institute for Applied Cancer Research at Kaiser Franz Josef Hospital
Vienna, Austria, A-1100
St. Johanns-Spital
Salzburg, Austria, A-5020
Belgium
AZ Groeninge - Oncologisch Centrum
Kortrijk, Belgium, 8500
Institut Jules Bordet
Brussels, Belgium, 1000
Onze Lieve Vrouw Ziekenhuis Aalst
Aalst, Belgium, B-9300
Universitair Ziekenhuis Antwerpen
Edegem, Belgium, B-2650
Denmark
Rigshospitalet - Copenhagen University Hospital
Copenhagen, Denmark, 2100
Germany
Klinikum Nuernberg - Klinikum Nord
Nuernberg, Germany, D-90419
Hungary
National Institute of Oncology
Budapest, Hungary, 1125
Israel
Assaf Harofeh Medical Center
Zerifin, Israel, 70300
Italy
Ospedale di Circolo e Fondazione Macchi
Varese, Italy, 21100
Universita Di Palermo
Palermo, Italy, 90145
Netherlands
Academisch Medisch Centrum at University of Amsterdam
Amsterdam, Netherlands, 1105 AZ
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, Netherlands, 5211 NL
Leiden University Medical Center
Leiden, Netherlands, 2300 CA
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
Amsterdam, Netherlands, 1066 CX
Universitair Medisch Centrum St. Radboud - Nijmegen
Nijmegen, Netherlands, NL-6500 HB
University Medical Center Rotterdam at Erasmus Medical Center
Rotterdam, Netherlands, 3000 CA
University Medical Center Utrecht
Utrecht, Netherlands, 3584 CX
Poland
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
Warsaw, Poland, 02-781
Spain
Hospital Clinic de Barcelona
Barcelona, Spain, 08036
Hospital de la Santa Cruz i Sant Pau
Barcelona, Spain, 08025
Hospital Universitario San Carlos
Madrid, Spain, 28040
Instituto Valenciano De Oncologia
Valencia, Spain, 46009
Vall d'Hebron University Hospital
Barcelona, Spain, 08035
United Kingdom, England
Leeds Cancer Centre at St. James's University Hospital
Southampton, England, United Kingdom, SO14 0YG
Southampton General Hospital
Southampton, England, United Kingdom, SO16 6YD
Royal South Hants Hospital
Southampton, England, United Kingdom, SO14 0YG
Royal Marsden - Surrey
Sutton, England, United Kingdom, SM2 5PT

Sponsors and Collaborators

European Organization for Research and Treatment of Cancer

Investigators

Study Chair:

Gerwin Kaiser, MD

Klinikum Nuernberg - Klinikum Nord

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

De Santis M, Bellmunt J, Mead G, Kerst JM, Leahy M, Maroto P, Skoneczna I, Marreaud S, de Wit R, Sylvester R. Randomized Phase II/III Trial Assessing Gemcitabine/Carboplatin and Methotrexate/Carboplatin/Vinblastine in Patients With Advanced Urothelial Cancer "Unfit" for Cisplatin-Based Chemotherapy: Phase II--Results of EORTC Study 30986. J Clin Oncol. 2009 Sep 28; [Epub ahead of print]

De Santis M, Bellmunt J, Mead B, et al.: Randomized phase II/III study assessing gemcitabine/carboplatin (GC) and methotrexate/carboplatin/vinblastine (M-CAVI) in previously untreated patients (pts) with advanced urothelial cancer ineligible for cisplatin based chemotherapy: phase II results of. [Abstract] American Society of Clinical Oncology 2008 Genitourinary Cancers Symposium, Feb 14-16, 2008, San Francisco, CA. A-288, 2008.

Study ID Numbers:	CDR0000068525, EORTC-GU-30986
Study First Received:	April 10, 2001
Last Updated:	October 1, 2009
ClinicalTrials.gov Identifier:	NCT00014274 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage III bladder cancer
stage IV bladder cancer
transitional cell carcinoma of the bladder
anterior urethral cancer

posterior urethral cancer
urethral cancer associated with invasive bladder cancer
metastatic transitional cell cancer of the renal pelvis and ureter
regional transitional cell cancer of the renal pelvis and ureter

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Ureteral Diseases
Urogenital Neoplasms
Vinblastine
Reproductive Control Agents
Urologic Neoplasms
Carcinoma, Transitional Cell
Neoplasms by Site
Urologic Diseases

Kidney Neoplasms
Therapeutic Uses
Abortifacient Agents
Urethral Diseases
Methotrexate
Kidney Diseases
Gemcitabine
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Neoplasms by Histologic Type
Mitosis Modulators
Urinary Bladder Diseases
Urinary Bladder Neoplasms
Enzyme Inhibitors
Antimitotic Agents

ClinicalTrials.gov processed this record on November 27, 2009