Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III, Phase II	Treatment	Closed	18 and over	Other	EORTC-GU-30986 NCT00014274

Objectives

1. 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.
2. Compare the toxicity and acute and intermediate (1-2 years) side effects of these regimens in these patients.
3. Compare the complete response rates, progression-free survival, and overall survival of patients treated with these regimens.
4. Compare the symptoms and quality of life of patients treated with these regimens.

Entry 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

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

Patient Characteristics:

Age:

• 18 and over

Performance status:

• See Disease Characteristics

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 4,000/mm³
• Platelet count at least 125,000/mm³

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

Expected Enrollment

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.

Outcomes

Duration of survival

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

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.

De Santis M, Bellmunt J, Mead G, et al.: 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.[PUBMED Abstract]

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.

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Gerwin Kaiser, MD, Protocol chair		Ph: 49-0911-398-3060

Registry Information
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
Trial Start Date		2001-01-17
Trial Completion Date		2009-05-31 (estimated)
Registered in ClinicalTrials.gov		NCT00014274 1
Date Submitted to PDQ		2001-02-06
Information Last Verified		2007-10-07

Table of Links

1	http://clinicaltrials.gov/ct/show/NCT00014274