Phase II Evaluation of Trastuzumab (Herceptin), Paclitaxel, Carboplatin, and Gemcitabine in the Treatment of Advanced Urothelial Cancer

National Cancer Institute (NCI)1 site in 1 country40 target enrollmentMarch 2000

ConditionsMetastatic Transitional Cell Cancer of the Renal Pelvis and Ureter Recurrent Bladder Cancer Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter Squamous Cell Carcinoma of the Bladder Stage IV Bladder Cancer Transitional Cell Carcinoma of the Bladder

Interventionstrastuzumab paclitaxel carboplatin gemcitabine hydrochloride laboratory biomarker analysis

Drugspaclitaxel carboplatin gemcitabine hydrochloride

Overview

Phase: Phase 2
Intervention: trastuzumab
Conditions: Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter
Sponsor: National Cancer Institute (NCI)
Enrollment: 40
Locations: 1
Primary Endpoint: Cardiac toxicity rate of this combination using MUGA or 2D ECHO
Status: Completed
Last Updated: 13 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Phase II trial to study the effectiveness of combining trastuzumab with combination chemotherapy in treating patients who have locally recurrent or metastatic urinary tract cancer. 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

Detailed Description

PRIMARY OBJECTIVES: I. To assess the toxicity of the combination of Herceptin, paclitaxel, carboplatin, and gemcitabine in patients with metastatic or locally recurrent urothelial cancers who overexpress HER2. SECONDARY OBJECTIVES: I. The complete and partial response rates. II. The median and overall survival. III. To prospectively evaluate the percentage of patients with metastatic/recurrent bladder cancer who overexpress HER2 histologically (by immunohistochemistry and FISH) and serologically. IV. To generate preliminary data on response to other therapy and survival for Her2 negative patients. 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.

Registry

clinicaltrials.gov

Start Date

March 2000

End Date

August 2004

Last Updated

13 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

National Cancer Institute (NCI)

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologic diagnosis of urothelial carcinoma (TCC or Squamous) that is either metastatic or locally recurrent and not curable by surgery or radiation therapy; patients must have HER2 overexpression as documented by ANY of the following:
•2+ or 3+ staining by immunohistochemistry, or
•a positive FISH score defined as \> 2 with the Vysis system or \> 4 with the Ventana system, or
•an elevated serum HER2 of \> 16 ng/ml using the OSDI assay; please note:
•Tissue from either the primary or metastatic site must be tested for HER2 status determination
•All patients must have a blood sample drawn for HER2 serologic testing
•If the available tissue is from the primary tumor and is HER2 negative and if the serum is negative, to qualify for the study a biopsy of a metastatic site should be done and the patient will be eligible ONLY if this demonstrates HER2 over-expression
•All sites and measurements of disease must be clearly documented in the pre-study forms
•All prior local or adjuvant systemic therapy including the type of chemotherapy must be clearly documented in the pre-study form Note: Patients with Her-2 negative tumors are not eligible for treatment on this protocol but their response to other therapy and survival will also be evaluated
•Bidimensionally measurable or evaluable disease not previously radiated

Exclusion Criteria

Not provided

Arms & Interventions

Treatment (trastuzumab, combination chemotherapy)

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.

Intervention: trastuzumab