A Study of Herceptin (Trastuzumab) Combination Therapy in Patients With Metastatic Urothelial Cancer

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of a chemotherapy regimen of intravenous Herceptin, cisplatin and gemcitabine in patients with metastatic urothelial cancer. The anticipated time on study treatment is until disease progression.

Official Title
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An Open-label Pilot Study Evaluating the Effect of a Combination Regimen of Herceptin, Cisplatin, and Gemcitabine on Time to Disease Progression in Patients With Metastatic Urothelial Cancer

Conditions
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Urinary Tract Cancer

Intervention / Treatment
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* Drug: trastuzumab
* Drug: gemcitabine
* Drug: cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients with >=18 years of age; metastatic urothelial carcinoma; measurable metastases or local recurrent disease; no prior chemotherapy for metastatic disease; HER2 overexpression (IHC [2+] or [3+]). Exclusion Criteria: concomitant chemotherapy or immunotherapy; active or uncontrolled infection; solely CNS metastases; clinically significant cardiac disease, advanced pulmonary disease or severe dyspnoea; co-existing malignancies diagnosed within last 5 years, except basal cell cancer or cervical cancer in situ.

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trastuzumab, Gemcitabine, Cisplatin<br>Participants received an initial loading dose of 4 milligrams per kilogram (mg/kg) trastuzumab intravenous (i.v.) on Day 3 of Cycle 1, followed by weekly doses of 2 mg/kg i.v until disease progression; 1200 mg per square meter (m2) gemcitabine i.v. on Days 1, 8, and 15 of Cycles 1 through 6; and 70 mg/m2 cisplatin i.v. on Day 2 of Cycles 1 through 6. | Drug: trastuzumab<br>* 4 mg/kg i.v., Day 3 of Cycle 1, followed by weekly doses of 2 mg/kg i.v., Day 1 of Cycle 2 until disease progression<br>* Other names: Herceptin;Drug: gemcitabine<br>* 1200 mg/m2 i.v. on Days 1, 8, and 15 of Cycle 1 through 6<br>Drug: cisplatin<br>* 70 mg/m2 i.v. on Day 2 of Cycles 1 through 6<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) - Percentage of Participants With an Event | PFS was defined as the time from the first dose of study treatment to the first documentation of objective tumor progression or death due to any cause. | Screening, Day 1 of Cycles 1 through 6, every 4 weeks until end of treatment, up to 33 months | 
| Progression-Free Survival - Time to Event | The median time, in months, from the first dose of study treatment to PFS event. | Screening, Day 1 of Cycles 1 through 6, every 4 weeks until end of treatment, up to 33 months | 
| Percentage of Participants Who Were Progression Free at 12 and 24 Months |  | Screening, and Months 12 and 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) - Percentage of Participants With an Event | OS was defined as the time from the start of study treatment to date of death due to any cause. | Screening, Day 1 of Cycles 1 through 6, every 4 weeks until end of treatment, up to 36 months | 
| Overall Survival - Time to Event | The median time, in months, from the start of study treatment to OS event. | Screening, Day 1 of Cycles 1 through 6, every 4 weeks until end of treatment, up to 36 months | 
| Percentage of Participants Surviving at 12 and 24 Months |  | Screening, and Months 12 and 24 | 
| Percentage of Participants Achieving Complete Response (CR), Partial Response (PR), or Stable Disease (SD) | Per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1): CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal [(short axis less than (<) 10 millimeters (mm)]. No new lesions. PR was defined as greater than or equal to (≥) 30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. SD was defined as not qualifying for CR, PR, or Progressive Disease (PD). | Screening, Day 1 of Cycles 1 through 6, every 4 weeks until end of treatment, up to 33 months |