Phase I Open Label Dose Escalation Study of the Safety and Pharmacokinetics of ME-143 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
- 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
- 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