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

Bladder Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00014274
• Other study ID #: EORTC-30986
• Secondary ID: EORTC-GU-30986
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: April 10, 2001
• Last updated: June 11, 2013
• Start date: January 2001

Study information

• Verified date: June 2013
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 238
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma, Transitional Cell
• Kidney Neoplasms
• Transitional Cell Cancer of the Renal Pelvis and Ureter
• Ureteral Neoplasms
• Urethral Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• carboplatin

• gemcitabine hydrochloride

• methotrexate

• vinblastine sulfate

Locations

Country	Name	City	State
Austria	St. Johanns-Spital	Salzburg
Austria	Ludwig Boltzmann Institute for Applied Cancer Research at Kaiser Franz Josef Hospital	Vienna
Belgium	Onze Lieve Vrouw Ziekenhuis Aalst	Aalst
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	AZ Groeninge - Oncologisch Centrum	Kortrijk
Denmark	Rigshospitalet - Copenhagen University Hospital	Copenhagen
Germany	Klinikum Nuernberg - Klinikum Nord	Nuernberg
Hungary	National Institute of Oncology	Budapest
Israel	Assaf Harofeh Medical Center	Zerifin
Italy	Universita Di Palermo	Palermo
Italy	Ospedale di Circolo e Fondazione Macchi	Varese
Netherlands	Jeroen Bosch Ziekenhuis	's-Hertogenbosch
Netherlands	Academisch Medisch Centrum at University of Amsterdam	Amsterdam
Netherlands	Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital	Amsterdam
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Universitair Medisch Centrum St. Radboud - Nijmegen	Nijmegen
Netherlands	University Medical Center Rotterdam at Erasmus Medical Center	Rotterdam
Netherlands	University Medical Center Utrecht	Utrecht
Poland	Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology	Warsaw
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital de la Santa Cruz i Sant Pau	Barcelona
Spain	Vall d'Hebron University Hospital	Barcelona
Spain	Hospital Universitario San Carlos	Madrid
Spain	Instituto Valenciano De Oncologia	Valencia
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Southampton	England
United Kingdom	Royal South Hants Hospital	Southampton	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Royal Marsden - Surrey	Sutton	England

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Austria,  Belgium,  Denmark,  Germany,  Hungary,  Israel,  Italy,  Netherlands,  Poland,  Spain,  United Kingdom, 

References & Publications (3)

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

De Santis M, Bellmunt J, Mead G, Kerst JM, Leahy M, Maroto P, Gil T, Marreaud S, Daugaard G, Skoneczna I, Collette S, Lorent J, de Wit R, Sylvester R. Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine — View Citation

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 ca — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of survival			No
Secondary	Response as assessed by RECIST criteria			No
Secondary	Toxicity as assessed by CTC v2			Yes