Dose Escalation Study of the Safety and Pharmacokinetics of ME-344 Single Agent for Refractory Solid Tumors

Phase 1 Open Label Dose Escalation Study of the Safety and Pharmacokinetics of ME-344 as a Single Agent in Patients With Refractory Solid Tumors

The purpose of this study is to determine the tolerability of ME-344, find the maximum tolerated dose, and the safety profile in patients with 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 (Appendix A)

• 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) < 2.5 x ULN for the reference laboratory or < 5 x ULN in the presence of liver metastases
  • Serum creatinine < 1.5 x ULN

• Adequate cardiac function as evidenced by:

  • CK-MB within normal levels at baseline
  • Troponin T within normal levels at baseline
  • The average QTc from triplicate screening ECGs (every 5 minutes over a total of 15 minutes) must be < 470 msec to be eligible for the study. (If a patient has an average QTc interval >470 msec at screening, the screening ECG may be repeated twice (at least 24 hours apart).
  • LV Ejection Fraction > lower limit of institutional normal level

• All potentially fertile patients will agree to use an effective form of contraception during the study and for 30 days following the last dose of ME-344 (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 nitrosourea 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, immunotherapy or following major surgery and any surgical incision should be completely healed. At least 14 days must have elapsed prior to Day 1 Cycle 1 for "limited palliative radiotherapy", defined as a course of therapy encompassing <25% total bone marrow volume and not exceeding 30 Gy.

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.

• Any major surgery, radiotherapy, or immunotherapy within the last 21 days. Limited palliative radiation, defined as encompassing <25% of total bone marrow volume and not exceeding a total dose of 30 Gy, within the last 14 days.

• 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-344 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.