Safety Study of PRLX 93936 in Patients With Advanced Solid Tumors

This study will assess the safety, pharmacokinetics, and pharmacodynamics of PRLX 93936 administered intravenously over 1 hr daily for 5 days in patients with advanced solid tumors. Patients will be evaluated prior to dosing, during dosing and following dosing, on a 28-day cycle. Tumor response will be evaluated every other cycle.

Three patients will be assigned per dose level until the Maximum Tolerated Dose (MTD) is reached or a a Dose-Limited Toxicity (DLT) is encountered. Sequential cohorts of three patients will be treated with escalating doses until the Maximum Tolerated Dose (MTD) is reached.

Inclusion criteria

• Histologically confirmed solid tumors
• Tumor progression after receiving standard/approved chemotherapy and for whom no available treatment provides clinical benefit
• One or more metastatic tumors measurable on a CT scan or MRI per RECIST criteria
• ECOG performance 0-1
• Life expectancy of at least 3 months
• Age >/= 18 years
• A negative pregnancy test (if female of child-bearing potential)
• Acceptable liver function:
• Bilirubin </= 1.5 times the Upper Limit of Normal (ULN)
• AST (SGOT), ALT (SGPT) and Alkaline phosphatase </= 2.5 times ULN (if liver metastases are present, then </= 5 times ULN is allowed)
• Acceptable renal function:
• Serum creatinine within normal limits, OR calculated creatinine clearance >/= 60 mL/min/1.73m2 for patients with creatinine levels above institutional normal
• Acceptable hematologic status:
• Granulocyte count >/= 1500 cells/mm3
• Platelet count >/= 100,000 (plt/mm3)
• Hemoglobin >/= 9.0 g/dL
• Urinalysis: no clinically significant abnormalities
• Acceptable coagulation status:
• PT within normal limits
• aPTT within normal limits
• Completed any chemotherapy, major surgery, or irradiation at least four weeks before enrollment in this study (six weeks for mitomycin-C or nitrosoureas, and two weeks for "targeted" therapies such as kinase inhibitors). Patient must have recovered from all toxicities incurred as a result of previous therapy.
• QT intervals of QTC </= 450 msec for men and </= 470 msec for women (as measured by Hodges equation)
• Left ventricular ejection fraction >/= 50% by 2D Echocardiogram (or > institutional lower limits of normal)

Exclusion criteria

• NYHA Class III or IV, cardiac disease, myocardial infarction within the past six months, unstable arrhythmia, or evidence of ischemia on ECG
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
• Pregnant or nursing women
• Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within four weeks prior to study entry (six weeks for mitomycin-C or nitrosoureas and two weeks for targeted therapies such as kinase inhibitors).
• Unwillingness or inability to comply with protocol procedures
• Known current infection with HIV, hepatitis B or hepatitis C
• Currently receiving any other investigational agent
• Currently receiving medications metabolized by the cytochrome P450 3A4 enzyme pathway
• Presence of clinically apparent central nervous system metastases or carcinomatous meningitis. Patients with brain metastases which are well controlled (patients not taking dexamethasone or anti-seizure medication >/= three months after treatment) may be enrolled.
• Any other severe concurrent disease, which in the judgement of the investigator would make the patient inappropriate for the study
• Diagnosis of hypertension
• Previously enrolled in this trial