An Open-Label, Multicenter Dose-Escalation Study to Evaluate the Safety and Tolerability of AP 12009 (Trabedersen), Administered Intravenously in Patients With Advanced Tumors Known to Overproduce TGF-β2.
The purpose of this dose-finding study is to evaluate the safety and tolerability of AP
12009. Two fixed dose-escalation schemes with predefined steps and increasing increments
have been selected to determine the maximum tolerated dose (MTD) as well as the
dose-limiting toxicity (DLT). At least two cycles of AP 12009 are administered intravenously
in adult patients with no further acknowledged treatment options.
AP 12009 (trabedersen) is a phosphorothioate antisense oligodeoxynucleotide specific for the
mRNA of human Transforming Growth Factor beta 2 (TGF-beta-2). The growth factor TGF-beta
plays a key role in malignant progression of various tumors by inducing proliferation,
invasion, metastasis, angiogenesis, and escape from immunosurveillance. In patients with
pancreatic cancer, colorectal cancer, and metastatic melanoma the TGF-beta-2 overexpression
is associated with disease stage, clinical prognosis, and the immunodeficient state of the
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the maximum tolerated dose (MTD) as well as the dose-limiting toxicity (DLT) of two cycles of AP 12009 administered intravenously at weekly intervals and for four days every other week.
Helmut Oettle, MD
Charité Berlin Campus Virchow-Klinikum
Germany: Federal Institute for Drugs and Medical Devices