Trastuzumab in Treating Patients With Previously Treated, Locally Advanced, or Metastatic Cancer of the Urothelium

Study Overview
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Brief Summary
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Phase II trial to study the effectiveness of trastuzumab in treating patients who have previously treated, locally advanced, or metastatic cancer of the urothelium. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

Detailed Description
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OBJECTIVES: I. Determine the response rate in patients with previously treated, locally advanced or metastatic transitional cell carcinoma of the urothelium treated with trastuzumab (Herceptin). II. Determine the safety of this drug in this patient population. III. Determine overall and progression-free survival of this patient population treated with this drug. OUTLINE: Patients receive a loading dose of trastuzumab (Herceptin) IV over 90 minutes on day 1 of week 1. For all subsequent doses, patients receive trastuzumab IV over 30 minutes weekly. Treatment may continue for more than 1 year in the absence of unacceptable toxicity or disease progression. Patients are followed every 3 months for 1 year and then every 6 months thereafter.

Official Title
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A Phase II Trial of Trastuzumab (Herceptin; NSC #688097, IND #6667) in Patients With Previously Treated Advanced Urothelial Tract Transitional Cell Carcinoma

Conditions
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Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter, Proximal Urethral Cancer, Recurrent Bladder Cancer, Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter, Recurrent Urethral Cancer, Stage IV Bladder Cancer, Transitional Cell Carcinoma of the Bladder, Urethral Cancer Associated With Invasive Bladder Cancer, Distal Urethral Cancer

Intervention / Treatment
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* Biological: trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed transitional cell carcinoma (TCC) of the urothelium, including the bladder, urethra, ureter, or renal pelvis No pure adenocarcinomas, pure squamous cell carcinomas, small cell carcinoma, or only small foci of TCC (less than 10% of tumor specimen) Locally advanced (T4b) TCC of the bladder Metastatic (N2 or N3 or M1)TCC of the urothelium HER2 expression (3+) as determined by immunohistochemistry or gene amplification by fluorescent in situ hybridization Must not be a candidate for potentially curative surgery or radiotherapy Measurable disease At least 1 unidimensionally measurable lesion of at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan The following lesions are considered nonmeasurable: Bone lesions Leptomeningeal disease Ascites Pleural/pericardial effusion Lymphangitis cutis/pulmonis Abdominal masses not confirmed and followed by imaging techniques Cystic lesions Primary bladder masses Relapsed from or failed to achieve a complete or partial response after 1 prior systemic chemotherapy regimen for TCC, including cisplatin, carboplatin, paclitaxel, docetaxel, or gemcitabine Prior adjuvant or neoadjuvant chemotherapy is considered 1 prior chemotherapy regimen Prior single-agent chemotherapy as a radiosensitizer is not considered a prior systemic chemotherapy regimen No known brain metastases Performance status - CTC 0-2 More than 12 weeks Absolute neutrophil count at least 1,000/mm^3 Platelet count at least 75,000/mm^3 Bilirubin no greater than 2 times upper limit of normal (ULN) AST no greater than 2 times ULN Creatinine clearance at least 30 mL/min Ejection fraction at least 50% (or lower limit of normal) by echocardiogram or MUGA No history of ongoing congestive heart failure No active cardiac ischemia Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix HIV negative No known autoimmune disease No prior trastuzumab (Herceptin) At least 14 days since prior radiotherapy At least 30 days since prior chemotherapy Prior doxorubicin allowed provided cumulative dose is no greater than 300 mg/m^2 Prior epirubicin allowed provided cumulative dose is no greater than 600 mg/m^2 No concurrent chemotherapy No concurrent hormonal therapy except: Steroids given for adrenal failure Hormones administered for nondisease-related conditions (e.g., insulin for diabetes) Intermittent dexamethasone as an antiemetic or for sensitivity reactions to study drug No concurrent palliative radiotherapy Prior radiotherapy allowed provided treated area is not only site of measurable disease At least 14 days since prior surgery

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: Treatment: Herceptin<br>Patients receive a loading dose of trastuzumab (Herceptin) IV over 90 minutes on day 1 of week 1. For all subsequent doses, patients receive trastuzumab IV over 30 minutes weekly. Treatment may continue for more than 1 year in the absence of unacceptable toxicity or disease progression. | Biological: trastuzumab<br>* Given IV<br>* Other names: MOAB HER2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (complete or partial response) as assessed by RECIST criteria |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicities as graded according to the NCI Common Toxicity Criteria |  | 12 weeks | 
| Proportion of patients who are HER2 positive (3+ by IHC or FISH positive) |  | Baseline | 
| Overall survival (OS) |  | From date of initiation of treatment to date of death due to any cause, assessed up to 1 year | 
| Disease-free survival (DFS) |  | From date of initiation of treatment to date of progression or death due to any cause, whichever occurs first, assessed up to 1 year |