dose escalation study of the safety and pharmacokinetics of me-344 single agent for refractory solid tumors

Conditions: Solid Tumors

Summary: 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.


Eligibility criteria:
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 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.

Keywords: solid tumors recurrent advanced metastatic refractory