RATIONALE: Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with combination chemotherapy may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining trastuzumab with combination chemotherapy in treating patients who have locallyrecurrent or metastaticurinary tract cancer.

Condition	Treatment or Intervention	Phase
Bladder Cancer transitional cell cancer of the renal pelvis and ureter Urethral Cancer	Drug: carboplatin  Drug: gemcitabine  Drug: paclitaxel  Drug: trastuzumab  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: monoclonal antibody therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the toxicity of the combination of trastuzumab (Herceptin), paclitaxel, carboplatin, and gemcitabine in patients with HER2-overexpressing locally recurrent or metastatic urothelial carcinoma.
• Determine the complete and partial response rates in patients treated with this regimen.
• Determine the median and overall survival of patients treated with this regimen.

OUTLINE: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, and 15; paclitaxel IV over 3 hours and carboplatin IV over 15 minutes on day 1; and gemcitabine IV over 30 minutes on days 1 and 8. Courses repeat every 3 weeks. Patients achieving a complete response (CR) receive 3 courses past CR. Patients achieving a partial response or stable disease continue on therapy until CR or disease progression or unacceptable toxicity.

Patients are followed for disease progression and survival. Patients with HER2-negative disease are not eligible for treatment but are followed every 6 months for response and survival.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 24 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed locally recurrent or metastatic urothelial carcinoma incurable by surgery or radiotherapy
• Transitional cell OR squamous cell
• HER2 overexpression of the primary or metastatic site evidenced by 1 of the following:
• 2+ or 3+ staining by immunohistochemistry
• Positive FISH defined as greater than 2 with the Vysis system or greater than 4 with the Ventana system
• Elevated serum HER2 greater than 16 ng/mL with the OSDI assay
• Biopsy-proven HER2 overexpression of metastatic site if primary site is histologically and serologically HER2 negative*
• Bidimensionally measurable or evaluable disease
• Disease outside previously irradiated fields NOTE: *HER2-negative patients are not eligible for treatment but are followed for response and survival

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• SWOG 0-2

Life expectancy:

• More than 12 weeks

Hematopoietic:

• Granulocyte count greater than 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No significant cardiac disease
• Ejection fraction at least 50% by MUGA or 2D echocardiogram
• No evidence of symptomatic coronary artery disease
• No active ischemia on EKG
• No history of congestive heart failure

Other:

• No active bacterial infection
• No other prior malignancy except adequately treated basal or squamous cell skin cancer or carcinoma in situ
• HIV negative
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• No prior systemic chemotherapy for metastatic disease
• At least 6 months since prior adjuvant chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered

Surgery:

• See Disease Characteristics

Arizona
      Mayo Clinic Scottsdale, Scottsdale,  Arizona,  85259,  United States
California
      University of California Davis Cancer Center, Sacramento,  California,  95817,  United States
Colorado
      University of Colorado Cancer Center at University of Colorado Health Sciences Center, Denver,  Colorado,  80010,  United States
Michigan
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0942,  United States
New York
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States
Ohio
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States
Pennsylvania
      Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15213-3489,  United States

Study chairs or principal investigators

Maha Hadi A. Hussain, MD,  Study Chair,  University of Michigan Comprehensive Cancer Center   

Study ID Numbers:  CDR0000067845; CCUM-9955; WSU-C-2078; NCI-198
Record last reviewed:  October 2004
Last Updated:  October 13, 2004
Record first received:  June 2, 2000
ClinicalTrials.gov Identifier:  NCT00005831
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08