Effect on QTc, Pharmacokinetics, Safety, and Preliminary Efficacy of Single-agent Palifosfamide-tris in Subjects With Advanced Solid Tumors

This is an open-label study of palifosfamide-tris administered intravenously on Days 1, 2, and 3 of a 21-day cycle to subjects with advanced solid tumors. Enrolled subjects will receive a placebo-control infusion on Day -1 and then commence palifosfamide-tris study treatment 24 hours later on Day 1. Time-matched, intensive ECG monitoring will occur during and following placebo and palifosfamide-tris infusions on Days -1, 1, 2, 3 and 8. Generation of ECG data for study analysis will be performed in a blinded fashion at a central ECG laboratory. Blood and urine sampling to characterize the pharmacokinetics of palifosfamide-tris will be performed on Days 1 through 8 of Cycle 1.

Inclusion criteria: 1. Male or female subjects, age ≥ 18 years, who have provided written informed consent prior to completing any study specific procedure. 2. Histologically or cytologically confirmed solid tumor that has progressed following available standard therapies or for which no standard therapy exist. 3. Measurable or non-measurable disease by RECIST version 1.1 4. Must have recovered from toxic effects of prior cancer treatment to ≤ Grade1per CTCAE v4.0, with the exception of any alopecia. 5. ECOG Performance Status of 0 or 1. 6. Adequate bone marrow, liver, and renal function, as assessed by the following laboratory requirements: 1. Hemoglobin ≥9.0 g/dL. 2. Absolute neutrophil count (ANC) ≥1,500/uL. 3. Platelet count ≥100,000/uL. 4. Total bilirubin ≤1.5 x upper limit of normal (ULN) 5. ALT and AST ≤2.5 x ULN. For subjects with documented liver metastases, ALT and AST ≤5×ULN. 6. International Normalized Ratio (INR) and activated partial thromboplastin time \[PTT\] \500ms on repeat measurements (e.g., 2 out of 3 ECGs), or bradycardia (defined as ≤ 50 beats/minute). 10. Subjects who will be receiving medications that prolong the QT interval with a risk of causing Torsades de Pointes during the time period beginning 1 week prior to and during the Intensive ECG monitoring period (i.e., Cycle 1, Day -8 through Day 8).