This study will evaluate thrice weekly dosing with vintafolide to find the maximum tolerable dose. The primary study hypothesis is that administration of vintafolide to participants with advanced solid tumors will have acceptable safety and tolerability.

Inclusion Criteria:

• Histologically-confirmed metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ function

Exclusion Criteria:

• Chemotherapy, radiotherapy, or biological therapy (including monoclonal antibodies) within 4 weeks prior to drug administration (6 weeks for nitrosoureas or mitomycin C) or not recovered from adverse events due to agents administered more than 4 weeks earlier
• Primary central nervous system (CNS) tumor
• Active CNS metastases and/or carcinomatous meningitis
• Known hypersensitivity to the components of the study therapy or its analogs
• Recent history of abdominal surgery or peritonitis
• Bowel occlusion or sub occlusion
• Prior abdominal or pelvis radiation therapy or radiation therapy to > 10% of the bone marrow at any time in the past or prior radiation therapy within the last three years to the breast / sternum, head, or neck
• Requires anti-folate therapy
• Symptomatic ascites or pleural effusion
• Prior stem cell or bone marrow transplant