Clinical trial NCT00014274: Combination Chemotherapy in Treating Patients With Transitional Cell Cancer of the Urothelium
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Bladder Cancer
Transitional Cell Cancer of the Renal Pelvis and Ureter
Urethral Cancer
Keywords: 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
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 238
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Duration of survival
Secondary outcomes:
measure: Response as assessed by RECIST criteria
measure: Toxicity as assessed by CTC v2
Other outcomes:
Locations:
city: Salzburg
country: Austria
facility: St. Johanns-Spital
city: Vienna
country: Austria
facility: Ludwig Boltzmann Institute for Applied Cancer Research at Kaiser Franz Josef Hospital
city: Aalst
country: Belgium
facility: Onze Lieve Vrouw Ziekenhuis Aalst
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Kortrijk
country: Belgium
facility: AZ Groeninge - Oncologisch Centrum
city: Copenhagen
country: Denmark
facility: Rigshospitalet - Copenhagen University Hospital
city: Nuernberg
country: Germany
facility: Klinikum Nuernberg - Klinikum Nord
city: Budapest
country: Hungary
facility: National Institute of Oncology
city: Zerifin
country: Israel
facility: Assaf Harofeh Medical Center
city: Palermo
country: Italy
facility: Universita Di Palermo
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondazione Macchi
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum at University of Amsterdam
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St. Radboud - Nijmegen
city: Rotterdam
country: Netherlands
facility: University Medical Center Rotterdam at Erasmus Medical Center
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
city: Barcelona
country: Spain
facility: Hospital de la Santa Cruz i Sant Pau
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario San Carlos
city: Valencia
country: Spain
facility: Instituto Valenciano De Oncologia
city: Southampton
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Southampton
country: United Kingdom
facility: Royal South Hants Hospital
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden - Surrey
state: England
Study officials:
affiliation: Klinikum Nuernberg - Klinikum Nord
name: Gerwin Kaiser, MD
role: STUDY_CHAIR
References:
citation: 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 in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol. 2012 Jan 10;30(2):191-9. doi: 10.1200/JCO.2011.37.3571. Epub 2011 Dec 12.
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 cancer "unfit" for cisplatin-based chemotherapy: phase II--results of EORTC study 30986. J Clin Oncol. 2009 Nov 20;27(33):5634-9. doi: 10.1200/JCO.2008.21.4924. Epub 2009 Sep 28.
citation: 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.