Study of Pralatrexate to Treat Advanced or Metastatic Relapsed Transitional Cell Carcinoma of the Urinary Bladder

Exclusion Criteria

• •Active concurrent primary malignancy or prior malignancies occurring within 5 years (except non-melanoma skin cancer, in situ carcinoma of the cervix, or occult, indolent carcinoma of the prostate). If there is a history of prior malignancies other than those exceptions listed above, the patient must be disease free for ≥ 5 years. Patients with other prior malignancies \< 5 years before study entry may still be enrolled if they have received treatment resulting in complete resolution of the cancer and currently have no clinical, radiologic, or laboratory evidence of active or recurrent disease. In the case of a single extrapelvic metastatic site, irrespective of the patient having a history of previous malignancy, a biopsy proof of the metastatic diseased organ will be necessary.
• •More than 1 previous regimen for recurrent/metastatic disease.
• •Evidence of clinically significant active third-space phenomenon
• •Use of investigational drugs, biologics, or devices within 28 days prior to study enrollment.
• •Previous exposure to other antifolates, including pralatrexate. Previous methotrexate is allowed, only if it was part of an M-VAC or MCV regimen.
• •Women who are pregnant or breastfeeding.
• •Congestive Heart Failure Class III/IV according to New York Heart Association (NYHA) Functional Classification.
• •Uncontrolled hypertension.
• •Human immunodeficiency virus (HIV)-positive diagnosis with a CD4 count of \< 100 mm3 or detectable viral load within the past 3 months, and receiving combination anti-retroviral therapy.
• •Central nervous system metastatic disease.
• •Major surgery within 2 weeks of study enrollment.
• •Radiation therapy (RT) within 4 weeks (within 3 months for RT to the pelvis) prior to study enrollment.
• •Active infection or any serious underlying medical condition, which would impair the ability of the patient to receive protocol treatment.
• •Dementia or significantly altered mental status that would prohibit the understanding and giving of informed consent or limit study compliance.