Trastuzumab (Herceptin), Paclitaxel, Carboplatin and Gemcitabine in Advanced Urothelial Cancer

Study Overview
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Brief Summary
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Purpose: The purpose of this study is to evaluate the efficacy and safety of treatment with trastuzumab (Herceptin) along with the three other chemotherapy drugs, paclitaxel, carboplatin and gemcitabine, in patients who have advanced urothelial cancer. This clinical trial will also collect information (alternative therapy, response rates, overall survival) from enrolled patients with HER2 negative tumors who are ineligible to receive study treatment.

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

Conditions
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Urologic Neoplasms

Intervention / Treatment
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* Drug: Trastuzumab
* Drug: Paclitaxel
* Drug: Carboplatin
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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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. All patients must have tissue from either the primary or metastatic site tested for HER2 status determination. Patients with Her-2 negative tumors are not eligible for treatment on this protocol. 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. Patients may not have received prior systemic chemotherapy for metastatic disease. Patients may have received adjuvant chemotherapy if completed at least 6 months prior to beginning this protocol treatment. Patients may not have cardiac disease and must have adequate cardiac function (ejection fraction > 50% or higher than the lower limit of institutional normal) as determined by a MUGA scan or 2-D echocardiogram within 4 weeks from registration, and no evidence of symptomatic coronary artery disease (baseline EKG must show no active ischemia). Patients must not have history of congestive heart failure. If patients have received prior radiation therapy, disease must be present outside of radiated fields and at least 4 weeks must have elapsed since discontinuation of that therapy. Exclusion Criteria: Pregnant or lactating women may not participate. HIV - positive patients may not participate. This is to avoid additional complications that immune suppression and HIV infection may cause due to the intense nature of the chemotherapy in this trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Herceptin<br>Herceptin - 4mg/kg day 1 of cycle 1; 2mg/kg day 8 and 15 of cycle 1 and subsequent cycles. Paclitaxel - 200mg/m^2 on day 1 Carboplatin - AUC 5 on day 1 Gemcitabine - 800 mg/m^2 on day 1 and 8 | Drug: Trastuzumab<br> <br> * Other names: Herceptin;Drug: Paclitaxel<br> <br> Drug: Carboplatin<br> <br> Drug: Gemcitabine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Toxicities Experienced by Treated Patients | The primary objective of the study is to evaluate the toxicity profile of combination of herceptin, paclitaxel, carboplatin and gemcitabine in patients with locally recurrent or metastatic urothelial carcinoma who overexpress HER2. | 30 Days Post Treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urothelial Cancer, Herceptin, Advanced Urothelial Cancer