Study of Gemcitabine and Cisplatin With or Without Cetuximab in Urothelial Cancer

Study Overview
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Brief Summary
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This study will compare the effects, good and/or bad, of chemotherapy (Gemcitabine and Cisplatin) with or without the addition of the chemotherapy drug Cetuximab to find out which treatment is better.

Detailed Description
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Urothelial cancer typically begins in the lining of the bladder, the balloon-shaped organ in the pelvic area that stores urine. Urothelial cancer can also begin in the ureter (the tube connecting the kidney and bladder), part of the kidney itself, or the urethra (the tube you pass urine out of). Some Urothelial cancers remain confined to the lining, while in other cases they spread to other areas. Treatment for these cancers varies greatly depending on the stage of disease at the time of diagnosis. Study participants in this research study will have a diagnosis of urothelial cancer that is advanced or has come back after prior therapy. There are two standard chemotherapeutic regimens for the management of this disease. One is the combination of the drugs, methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). However the toxicities associated with this treatment regimen (side effects) is high. The other is a combination of two drugs called Cisplatin and Gemcitabine. These drugs are also known to destroy urothelial cancer cells, and are better tolerated by patients. All study participants will receive both of these drugs. Another anti-cancer drug called Cetuximab is known to delay or prevent tumor growth and in some cases to lead to death of cancer cells by blocking certain cellular pathways that lead to tumor development. This drug has been approved by the United States Food and Drug Administration (FDA) for the treatment of colorectal cancer and for treatment of head and neck cancers. The use of Cetuximab for the treatment of urothelial cancer is investigational in this study. The purpose of this study is to compare the safety and efficacy of Gemcitabine and Cisplatin administered with or without the addition of Cetuximab in study participants with urothelial cancer. This is a randomized research study. Study participants will be randomized to receive either gemcitabine and cisplatin alone or in combination with Cetuximab.

Official Title
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Phase II Randomized Trial of Gemcitabine and Cisplatin With or Without Cetuximab in Patients With Urothelial Carcinoma

Conditions
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Bladder Cancer

Intervention / Treatment
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* Drug: Gemcitabine,
* Drug: Cisplatin
* Drug: Cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Study participants will be male or female at least 18 years of age Study participants will have a histologic/cytologic diagnosis of urothelial carcinoma (transitional cell carcinoma; either pure or mixed histology) that is metastatic, locally recurrent, or unresectable (T4bN0 or any T, N2030) Study participants must have measurable disease by radiologic imaging. Study participants that have received previous radiation therapy, recovered from side effects and have not had more than 25% of the bone marrow Study participants must have adequate bone marrow function Exclusion Criteria: Study participants may not have received previous systemic chemotherapy for the current stage of disease with the following exception: prior neoadjuvant or adjuvant chemotherapy is allowed provided it has been at least 6 months since treatment with non-cisplatin containing regimens and > 1 year since treatment with a cisplatin containing regimen Study participants may not have received prior therapy targeting the EGFR pathway Study participants may not have a history or known spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening CT or MRI scan Study participants may not have known HIV due to the intense nature of the chemotherapy in this trial Study subjects may not have a history of congestive heart failure (CHF), chronic renal failure, active TIAs, recent (in the last 6 months) stroke, symptomatic pulmonary embolism (PE), or myocardial infarction. Study participants with history of DVT or incidental or asymptomatic PE will be eligible for the study as deemed appropriate by the treating physician provided they continue prophylactic or full dose anticoagulation as per standards of care for the specific event. Study participants must not have a prior grade 3 or 4 severe infusion reaction to monoclonal antibodies Study participants may not be pregnant or breastfeeding Study participants may not receive concurrent treatment on another therapeutic clinical 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1, Gemcitabine and Cisplatin<br>Gemcitabine and Cisplatin, as described in the intervention | Drug: Gemcitabine,<br>* Gemcitabine will be administered intravenously at a dose of 1000 mg/m2 on Days 1, 8 and 15 of cycle. One treatment cycle is 28 days.<br>* Other names: Gemzar;Drug: Cisplatin<br>* Cisplatin will be administered intravenously at a dose of 70 mg/m2 per institutional standards on Day 1 of each cycle.<br>|
| Experimental: Arm 2, Cetuximab, Gemcitabine and Cisplatin<br>Gemcitabine and Cisplatin with Cetuximab, as described in the intervention | Drug: Gemcitabine,<br>* Gemcitabine will be administered intravenously at a dose of 1000 mg/m2 on Days 1, 8 and 15 of cycle. One treatment cycle is 28 days.<br>* Other names: Gemzar;Drug: Cisplatin<br>* Cisplatin will be administered intravenously at a dose of 70 mg/m2 per institutional standards on Day 1 of each cycle.<br>Drug: Cetuximab<br>* Cetuximab will be administered intravenously at a dose of 500 mg/m2 on Days 1 and 15 of each cycle. One treatment cycle is 28 days.<br>* Other names: Erbitux;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants That Respond to Treatment in Arm 1 and Arm 2 | The primary objective is to compare the overall response rate of participants with locally advanced or metastatic urothelial carcinoma treated with gemcitabine and cisplatin with or without cetuximab. Overall response rate is defined as the percentage of participants that experience Complete Response (CR) (Disappearance of all target lesions) or Partial Response (PR) (>=30% decrease in the sum of the longest diameter of target lesions). | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Grade 3 to 5 Adverse Events Experienced by Arm 1 and Arm 2 | One of the secondary outcomes was to assess the safety and tolerability of treatment for both arms. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 were utilized for adverse event reporting. | 3 years | 
| Median Progression-free Survival Time in Months | Progressive disease is defined as at least a 20% increase in the sum of the longest diameter of target lesions. | 3 years | 
| Median Overall Survival in Months | Median overall survival in months is provided. One participant who progressed from chemotherapy in arm 1 received cyclophosphamide and achieved long-term disease control therefore there is no upper limit for the 95% confidence interval. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bladder Cancer