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
- 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.
- 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