In this multinational dose finding Phase IIb study the efficacy and safety of two doses of AP 12009 compared to standard chemotherapy (temozolomide or PCV) is investigated in adult patients with confirmed recurrent high-grade glioma.
The purpose of this study is to compare the safety and efficacy of two doses of AP 12009 and standard chemotherapy in adult patients with recurrent high-grade glioma (anaplastic astrocytoma \[AA\], WHO grade III; or glioblastoma \[GBM\], WHO grade IV). AP 12009 is a phosphorothioate antisense oligodeoxynucleotide specific for the mRNA of human transforming growth factor-beta2 (TGF-beta2). 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. It has been shown that in a number of tumor types the degree of TGF-beta production strongly correlates with tumor grade and stage. In patients with high-grade glioma, the TGF-beta2 overexpression is associated with disease stage, clinical prognosis and the immunodeficient state of the patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
141
10 µM AP 12009 (trabedersen), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks
80 µM AP 12009 (trabedersen), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks
temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle; PCV (procarbazine, CCNU, vincristine): standard regimen
Overall response rate of two AP 12009 dose groups and control group assessed by the evaluation of tumor size on brain MRI scans
Overall survival
Time frame: overall
Overall survival
Time frame: six- and twelve-month
Response rates
Time frame: at 3, 8, 10, and 12 months (and during the prolonged follow-up period in six-monthly intervals, if applicable)
Progression-free survival
Time frame: six-month
Time to progression
Time to response
Best of all response rates assessed by survival status and variation of tumor size on brain MRI
Change of quality of life and Karnofsky Performance Status (KPS)
Time frame: at 3, 8, 10, and 12 months (and during the prolonged follow-up period in six-monthly intervals, if applicable)
Best of all response rates
Safety and tolerability
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Drug delivery system for Convection Enhanced Delivery consists of a portable pump with drug reservoir and infusion line. Main implanted parts are the port access system and the intratumoral catheter.
Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.
Universitätsklinik Innsbruck; Abteilung für Neurochirurgie
Innsbruck, Austria
Landes-Nervenklinik Wagner-Jauregg
Linz, Austria
Kaiser Franz Josef Spital, Abteilung für Neurologie
Vienna, Austria
Sarajishvili Institute of Clinical Neurology and Neurosurgery
Tbilisi, Georgia
Medizinische Klinik und Poliklinik mit Schwerpunkt Onkologie und Hämatologie, Charité Campus Mitte
Berlin, Germany
Klinik und Poliklinik für Neurologie
Cottbus, Germany
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
Dresden, Germany
Universitätsklinikum Gießen, Neurochirurgische Universitätsklinik
Giessen, Germany
Universitätsklinikum Kiel, Klinik für Neurochirurgie
Kiel, Germany
Universitätsklinikum Leipzig, Klinik und Poliklinik für Neurochirurgie
Leipzig, Germany
...and 26 more locations