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

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

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.

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.