RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining SCH 66336 and gemcitabine may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of SCH 66336 plus gemcitabine in treating patients who have advanced cancer of the urinary tract.

Condition	Treatment or Intervention	Phase
recurrent bladder cancer stage IV bladder cancer transitional cell carcinoma of the bladder recurrent urethral cancer anterior urethral cancer posterior urethral cancer urethral cancer associated with invasive bladder cancer metastatic transitional cell cancer of the renal pelvis and ureter recurrent transitional cell cancer of the renal pelvis and ureter	Drug: SCH 66336  Drug: gemcitabine  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the feasibility and toxicity of SCH 66336 and gemcitabine in patients with advanced transitional cell carcinoma of the urinary tract.
• Determine the time to progression and objective response rate of this treatment regimen in these patients.
• Assess the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 and oral SCH 66336 twice a day (starting on day 2 of the first course, and starting on day 1 of all subsequent courses). Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 8 weeks until disease progression.

PROJECTED ACCRUAL: A total of 7-31 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic or unresectable primary transitional cell carcinoma of the urinary tract, including bladder, ureter, and renal pelvis
• At least one measurable lesion
• 20 mm or greater by conventional techniques OR
• 10 mm or greater by spiral CT scan
• Must have received one (and only one) prior chemotherapy regimen for advanced or metastatic disease
• No clinical signs of brain metastases

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• Absolute neutrophil count at least 2,000/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase and transaminases no greater than 2.5 times ULN (no greater than 5 times ULN with liver metastases)

Renal:

• Creatinine no greater than 1.7 mg/dL

Cardiovascular:

• Normal cardiac function
• No ischemic heart disease within the past 6 months
• Normal 12 lead ECG

Other:

• No prior gastrectomy or any gastrointestinal disease that may impair absorption of SCH 66336
• No unstable systemic disease
• No active uncontrolled infection
• No psychological, familial, sociological, or geographical condition that would preclude study
• No prior or concurrent other malignancy except cone biopsied carcinoma in situ of the cervix or adequately treated basal or squamous cell skin cancer
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy
• No prior farnesyl protein transferase inhibitors or gemcitabine

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy

Surgery:

• At least 2 weeks since prior major surgery

Other:

• No other concurrent anticancer agents
• No other concurrent investigational therapy

Netherlands
      University Medical Center Nijmegen, Nijmegen,  6500,  Netherlands

Study chairs or principal investigators

Ronald De Wit, MD, PhD,  Study Chair,  Rotterdam Cancer Institute   
Pieter H.M. de Mulder, MD,  Study Chair,  University Medical Center Nijmegen   
Godefridus Peters, PhD,  Study Chair,  Vrije Universiteit Medisch Centrum   

Study ID Numbers:  CDR0000068217; EORTC-16997; EORTC-GU-16997; EORTC-PAMM-16997
Record last reviewed:  February 2003
Last Updated:  October 13, 2004
Record first received:  October 4, 2000
ClinicalTrials.gov Identifier:  NCT00006351
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08