In this national Phase I dose-escalation study the safety and tolerability of AP 12009 is evaluated in adult patients with advanced tumors known to overproduce TGF-β2, who are not or no longer amenable to established therapies.
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 patients.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
62
Initial scheme: AP 12009 (trabedersen), dose escalation scheme, continuous intravenous infusion (7 days), every other week, up to 10 cycles. Modified scheme: AP 12009 (trabedersen), dose escalation scheme, continuous intravenous infusion (4 days), every other week, up to 10 cycles
Universitätsmedizin Berlin Charité
Berlin, Germany
Universitätsklinik und Poliklinik für Innere Medizin I
Halle, Germany
Hautklinik der Ruprecht-Karls-Universität Heidelberg
Heidelberg, Germany
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.
To determine the safety and tolerability of AP 12009 administered intravenously at weekly intervals and for four days every other week.
To assess the plasma pharmacokinetic profile of AP 12009 administered intravenously at weekly intervals and for four days every other week.
To establish a suitable determination method and to assess the urine pharmacokinetic profile of AP 12009 administered intravenously for four days every other week.
To determine the effect of AP 12009 administered intravenously at weekly intervals and for four days every other week on TGF-β2 plasma concentration levels.
To determine the potential antitumor activity of AP 12009 administered intravenously at weekly intervals and for four days every other week, as assessed by the effect on tumor size and tumor markers.
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Universitätsklinikum Schleswig-Holstein
Kiel, Germany
Krankenhaus rechts der Isar, II. Medizinische Klinik und Poliklinik
München, Germany
Universität Münster, Klinik und Poliklinik für Hautkrankheiten
Münster, Germany
Klinik und Poliklinik für Innere Medizin I
Regensburg, Germany
Klinik und Poliklinik für Dermatologie
Regensburg, Germany
Universitäts-Hautklinik, Sektion Dermatologische Onkologie
Tübingen, Germany
Universitätsklinikum Ulm, Zentrum für Innere Medizin
Ulm, Germany