A Phase I Study of PLX038 in Patients With Advanced Solid Tumors

Exclusion Criteria

• •Patients will be excluded if they have received previous chemotherapy, immunotherapy, radiotherapy or any other investigational therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) or 5 half-lives for targeted therapies prior to this study entry.
• •Have not recovered from adverse events (must be grade ≤1) due to agents administered more than 4 weeks earlier.
• •Known hypersensitivity to any study drug component.
• •Extensive prior radiotherapy, more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation.
• •Any concomitant condition that in the opinion of the investigator could compromise the objectives of this study and the patient's compliance.
• •Pregnant or lactating individuals.
• •Current malignancies of another type, with the exception of adequately treated in situ cervical cancer and basal cell skin cancer or other malignancies with no evidence of disease for 2 years or more.
• •Known history of HIV, HBV or HCV infection.
• •Documented or known bleeding disorder.
• •Requirement for anticoagulation treatment that increases INR or aPTT above the normal range (low dose DVT or line prophylaxis is allowed).
• •Clinically evident CNS metastases or leptomeningeal disease not controlled by prior surgery or radiotherapy; history of seizure disorder not controlled by anti-seizure medication at the time of enrollment. Patients with primary CNS malignancies are excluded.
• •Patients with a significant cardiovascular disease or condition, including:
• •* Myocardial infarction within 6 months of study entry
• •* NYHA Class III or IV heart failure
• •* Uncontrolled dysrhythmias or poorly controlled angina.
• •* History of serious ventricular arrhythmia (VT or VF, ≥ 3 beats in a row) and/or risk factors (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
• •* Baseline prolongation of QT/QTc interval (repeated demonstration of QTc ≥ 450 msec for men and 470 msec for women), or LVEF ≤ 40% by MUGA or ECHO.
• •History of clinically significant gastrointestinal bleeding, colitis, or gastrointestinal perforation.
• •Patients who require treatment with UGT1A1 inhibitors during the period of investigational treatment with DFP-13318.
• •Patients with known Gilbert's syndrome or reduced UGT1A1 activity.