Pemetrexed Plus Cisplatin Bi-Weekly, in Patients With Urothelial Cancer (Metastatic, Locally Advanced or Non-Resectable)

Study Overview
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Brief Summary
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To assess the anti-tumor activity, as measured by response rate to bi-weekly pemetrexed plus cisplatin, in chemo-naive patients with diagnosed metastatic or locally advanced (non-resectable) urothelial cancer.

Official Title
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Phase 1/2 Study of Biweekly ALIMTA Plus Cisplatin in Patients With Locally, Advanced, Non-Resectable or Metastatic Urothelial Cancer

Conditions
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Urologic Neoplasms

Intervention / Treatment
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* Drug: pemetrexed
* Drug: cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven locally advanced disease or metastatic transitional cell carcinoma of the urothelium including bladder, urethra, ureter, and renal pelvis. Patients should not be suitable for surgery or radiation with curative intent. However patients whose pre-chemotherapy sites of disease are restricted to the primary or regional lymph node sites and who have a major response to chemotherapy will be evaluated for post-chemotherapy surgical resection of residual cancer if the tumor has become resectable at the end of chemotherapy. Measurable disease status, as defined in the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (Therasse et al., 2000) One course of prior radiation therapy is allowed. Prior radiation must have been completed at least 4 weeks before enrolment into the study and the patients must have recovered from all toxic effects. Exclusion Criteria: Have central nervous system (CNS) or leptomeningeal metastases (unless the patient has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before starting study therapy). A screening computed tomography (CT) or magnetic resonance imaging (MRI) before enrollment in the absence of a clinical suspicion of brain metastases is not required. Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents 2 days before, the day of, and 2 days after the dose of pemetrexed plus cisplatin or cisplatin alone. If a patient is taking a nonsteroidal anti-inflammatory drug (NSAID) or salicylate with a long half-life (for example, naproxen, piroxicam, diflunisal) it should not be taken 5 days before the dose of pemetrexed (8-day period for long-acting agents such as piroxicam), the day of, and 2 days after the dose of pemetrexed plus cisplatin.

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: Pemetrexed + Cisplatin<br> | Drug: pemetrexed<br>* Phase 1: 300 mg/m^2, intravenous (IV), days 1 and 15 every 28 days x 2 cycles (dose escalation: 300 mg/m^2, 400 mg/m^2, and 500 mg/m^2) Phase 2: phase 1 determined dose, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy<br>* Other names: Alimta;Drug: cisplatin<br>* Phase 1: 50 mg/m^2, intravenous (IV), days 1 and 15 every 28 days x 2 cycles Phase 2: 50 mg/m^2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Tumor Response | Best response recorded from the start of treatment until disease progression/recurrence using Response Evaluation Criteria In Solid Tumors (RECIST) criteria that defines when participants improve (respond), stay the same (stable), or worsen (progression) during treatment. Complete response (CR) = disappearance of all target lesions. Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions. Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions. Stable disease (SD) = small changes that do not meet above criteria. | baseline to measured progressive disease (up to 620 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Response | Defined as time from study enrollment to the first Complete Response or Partial Response (using RECIST criteria). Complete response (CR) = disappearance of all target lesions. Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions. | baseline to response (up to 620 days) | 
| Duration of Response | The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause. Complete response (CR) = disappearance of all target lesions. Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions. | time of response to progressive disease (up to 620 days) | 
| Duration of Stable Disease | Defined as time from study enrollment to the first progression of disease, complete response, partial response, or death from any cause. Complete response (CR) = disappearance of all target lesions. Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions. Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions. Stable disease (SD) = small changes that do not meet above criteria. | time of no response or progression (up to 620 days) | 
| Time to Progressive Disease | Defined as the time from study enrollment to the first date of disease progression. Time to disease progression was censored at the date of death if death was due to other cause. Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions. | baseline to measured progressive disease (up to 620 days) | 
| Time to Treatment Failure (TTF) | Time from study enrollment to first observation of disease progression, death from any cause, or early discontinuation of treatment (including toxicity or if patient had stable disease after 4 cycles). TTF was censored at date of last follow-up visit for patients who did not discontinue early, who were still alive, and who had not progressed. | baseline to stopping treatment (up to 620 days) | 
| Progression-Free Survival | Defined as the time from study enrollment until disease progression or death from any cause. | baseline to measured progressive disease (up to 620 days) | 
| Overall Survival | Overall survival is the duration from enrollment to death. For patients who are alive, overall survival is censored at the last contact. | baseline to date of death from any cause (up to 620 days) |