Combination Chemotherapy in Treating Patients With Transitional Cell Cancer of the Urothelium

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Completed

CT.gov ID

NCT00014274

Collaborator

(none)

238

Enrollment

Locations

8.2

Patients Per Site

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Bladder Cancer Transitional Cell Cancer of the Renal Pelvis and Ureter Urethral Cancer	Drug: carboplatin Drug: gemcitabine hydrochloride Drug: methotrexate Drug: vinblastine sulfate	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

238 participants

Allocation:

Randomized

Primary Purpose:

Treatment

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

Study Start Date :

Jan 1, 2001

Actual Primary Completion Date :

Mar 1, 2008

Outcome Measures

Primary Outcome Measures

Duration of survival []

Secondary Outcome Measures

Response as assessed by RECIST criteria []
Toxicity as assessed by CTC v2 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

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