Phase I Dose Escalation Study of the Safety and Pharmacokinetics of ME-143 Single Agent for Refractory Solid Tumors

Inclusion Criteria:

• Provision of informed consent
• Male or female ≥18 years of age
• Histologic or cytologic confirmed locally advanced or metastatic cancer that has no standard therapeutic alternatives.
• ECOG Performance status 0-1
• A minimum life expectancy of 12 weeks

• Adequate bone marrow, hepatic and renal function as evidenced by

  • Absolute neutrophil count (ANC) > 1.5 x 109/L
  • Platelet count > 100 x 109/L
  • Hemoglobin > 9.0 g/dL
  • Serum bilirubin < 1.5 x ULN
  • AST/ALT (SGOT/SGPT) < or = 2.5 x ULN for the reference laboratory or < 5 x ULN in the presence of liver metastases
  • Serum creatinine < or = 1.5 x ULN
  • Follicle-Stimulating Hormone (FSH) within normal baseline levels
  • Male patients should have a detectable level of testosterone
• Female patients who are known to be capable of conception should have a negative serum pregnancy test (beta-human chorionic gonadotropin β-hCG]) within 1 week of starting the study.
• All potentially fertile patients will agree to use an effective form of contraception during the study and for 90 days following the last dose of ME-143 (an effective form of contraception is defined as an oral contraceptive or a double barrier method).
• At least 4 weeks must have elapsed prior to Day 1 Cycle 1 since prior chemotherapy (6 weeks for carmustine or mitomycin C), investigational drug or biologic therapy and any toxicity associated with these treatments has recovered to ≤ NCI-CTCAE Grade 1.
• At least 21 days must have elapsed prior to Day 1 Cycle 1, radiotherapy (limited palliative radiation is allowed > 2 weeks), immunotherapy or following major surgery and any surgical incision should be completely healed

Exclusion Criteria:

• Patients who are pregnant or breastfeeding
• Tumor involvement of the Central Nervous System (CNS) Patients with treated and stable CNS metastases may be eligible to participate after discussion and approval from the Medical Monitor
• Uncontrolled infection or systemic disease.
• Clinically significant cardiac disease not well controlled with medication (e.g., congestive heart failure, symptomatic coronary artery disease e.g. angina, and cardiac arrhythmias) or myocardial infarction within the last 12 months.
• Patients with QTc of > 470 msec on screening ECG. (If a patient has QTc interval >470 msec on screening ECG, the screening ECG may be repeated twice (at least 24 hours apart). The average QTc from the 3 screening ECGs must be <470 msec in order for the patient to be eligible for the study.
• Any major surgery, radiotherapy, or immunotherapy within the last 21 days (limited palliative radiation is allowed > 2 weeks).
• Chemotherapy regimens with delayed toxicity within the last 4 weeks (or within 6 weeks for prior nitrosourea or mitomycin C). Chemotherapy regimens given continuously or on a weekly basis with limited potential or delayed toxicity within the last 2 weeks.
• No concurrent systemic chemotherapy or biologic therapy is allowed.
• Known hypersensitivity to any components of ME-143 study drug product.
• Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated or both).
• History of solid organ transplantation.
• Psychiatric disorder or social or geographic situation that would preclude study participation.