Pemetrexed and Cisplatin in Advanced Urothelial Carcinoma

Study Overview
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Brief Summary
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Pemetrexed has demonstrated a favorable response with minimal toxicity when used as single agent as first-line and second-line treatment for advanced urothelial carcinoma. The response rates were 32% and 28% for the first-line and second-line setting, respectively. Cisplatin is one the most active chemotherapeutic agents in urothelial cancer, frequently used as combination chemotherapy such as GP (gemcitabine plus cisplatin) or MVAC (methotrexate, vinblastine, adriamycin, and cisplatin). Pemetrexed and cisplatin showed favorable activity profile in advanced non-small cell lung cancer with highly favorable toxicity profile. This study is to assess the efficacy and safety of pemetrexed plus cisplatin in advanced urothelial carcinoma.

Official Title
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A Prospective Phase 2 Study of PEmetrexed in Combination With Cisplatin in Patients With Advanced UrotheLIal CAnceR

Conditions
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Urothelial Carcinoma

Intervention / Treatment
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* Drug: Pemetrexed
* Drug: Cisplatin
* Drug: Dexamethasone
* Drug: Vitamins


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic or cytologic diagnosis of urothelial (transitional cell) carcinoma with the exception of micropapillary subtype Patients must have recurrent disease (locally advanced or metastatic) that is not amenable to local therapy or newly diagnosed distant metastatic disease Measurable disease defined by RECIST v.1.0 ECOG performance status of 2 or better Adequate organ and bone marrow function defined as Exclusion Criteria: Other tumor type than urothelial carcinoma Presence or history of CNS metastasis Prior systemic chemotherapy or immunotherapy (but prior local intravesical chemotherapy or immunotherapy was allowed. And recurrent disease after adjuvant or neoadjuvant cisplatin-based systemic chemotherapy is allowed if the last chemotherapy was administered 1 year or more before the patient enrollment.) Presence of second primary malignancy (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin) Peripheral sensory neuropathy grade 2 or worse Other serious illness or medical conditions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: PemCis<br>Pemetrexed plus Cisplatin | Drug: Pemetrexed<br>* Pemetrexed 500 mg/m2 IV over 10 minutes on D1 every 3 weeks<br>* Other names: Alimta;Drug: Cisplatin<br>* Cisplatin 70 mg/m2 IV over 60 minutes on D1 every 21 days<br>* Other names: cisplan;Drug: Dexamethasone<br>* Dexamethasone 4 mg bid PO from D-1 to D2 every 3 weeks<br>* Other names: Dexa;Drug: Vitamins<br>* Folic acid 350 ug - 600 ug daily from D-7 daily vitamin B12 1,000 ug every 9 weeks from D-7<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | Based on RECIST v.1.0 | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | 12 months | 
| Overall survival |  | 12 months | 
| Safety | Based on NCI CTCAE v.3.0 | 8 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced urothelial carcinoma