Phase IIb Clinical Trial With TGF-β2 Antisense Compound AP 12009 for Recurrent or Refractory High-grade Glioma
- Conditions
- GlioblastomaAnaplastic Astrocytoma
- Interventions
- Device: Drug delivery system for administration of AP 12009Procedure: Placement of Drug Delivery System
- Registration Number
- NCT00431561
- Lead Sponsor
- Isarna Therapeutics GmbH
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 141
- Histopathologically confirmed diagnosis of recurrent or refractory high-grade glioma (anaplastic astrocytoma, WHO grade III; or glioblastoma, WHO grade IV)
- Supratentorial localization
- No more than two chemotherapy regimens including radiochemotherapy since primary diagnosis
- Eligible for either TMZ or PCV treatment
- Recovery from acute toxicity caused by any previous therapy
- Adequate organ functions
- KPS at least 70%
- Tumor surgery within 2 weeks prior to study entry
- Radiation therapy within 8 weeks prior to study entry
- Chemotherapy within 4 weeks prior to study entry (nitrosureas: 6 weeks)
- No more than 3 mg/day dexamethasone (or equivalent) at baseline
- Prior TGF-beta targeted therapy or tumor vaccination
- Baseline MRI shows mass effect
- Known active infection with HIV, HBV, or HCV; acute viral, bacterial, or fungal infection
- Significant psychiatric disorders/legal incapacity or a limited legal capacity
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AP 12009 80 µM AP 12009 80 µM - AP 12009 80 µM Drug delivery system for administration of AP 12009 - AP 12009 80 µM Placement of Drug Delivery System - Chemotherapy temozolomide or PCV - AP 12009 10 µM AP 12009 10 µM - AP 12009 10 µM Drug delivery system for administration of AP 12009 - AP 12009 10 µM Placement of Drug Delivery System -
- Primary Outcome Measures
Name Time Method Overall response rate of two AP 12009 dose groups and control group assessed by the evaluation of tumor size on brain MRI scans
- Secondary Outcome Measures
Name Time Method Time to response Overall survival six- and twelve-month Response rates at 3, 8, 10, and 12 months (and during the prolonged follow-up period in six-monthly intervals, if applicable) Progression-free survival six-month Time to progression Best of all response rates assessed by survival status and variation of tumor size on brain MRI Best of all response rates Safety and tolerability Change of quality of life and Karnofsky Performance Status (KPS) at 3, 8, 10, and 12 months (and during the prolonged follow-up period in six-monthly intervals, if applicable)
Trial Locations
- Locations (36)
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
Universitätsklinik Magdeburg, Klinik für Neurochirurgie
🇩🇪Magdeburg, Germany
Universitätsklinik Innsbruck; Abteilung für Neurochirurgie
🇦🇹Innsbruck, Austria
Universitätsklinikum Kiel, Klinik für Neurochirurgie
🇩🇪Kiel, Germany
Universitätskliniken Mainz, Neurochirurgische Klinik und Poliklinik
🇩🇪Mainz, Germany
Klinikum und Poliklinik für Neurologie, Universität Regensburg
🇩🇪Regensburg, Germany
Neurologische Universitätsklinik Tübingen
🇩🇪Tübingen, Germany
Kaiser Franz Josef Spital, Abteilung für Neurologie
🇦🇹Wien, Austria
Universitätsklinikum Leipzig, Klinik und Poliklinik für Neurochirurgie
🇩🇪Leipzig, Germany
Sverdlovsk Regional Oncological Clinic
🇷🇺Ekaterinburg, Russian Federation
Klinikum Saarbrücken, Neurochirurgie
🇩🇪Saarbrücken, Germany
Department of Neurosurgery, LTMG Hospital & LTM Medical College
🇮🇳Mumbai, India
Manipal Hospital; Manipal Institute for Neurological Disorders
🇮🇳Bangalore, India
Universitätsklinikum Gießen, Neurochirurgische Universitätsklinik
🇩🇪Gießen, Germany
Universitätsklinikum Münster, Klinik und Poliklinik für Neurochirurgie
🇩🇪Münster, Germany
Department of Medical Oncology, Nizam's Institute of Medical Sciences
🇮🇳Hyderabad, India
Rambam Medical Center, Neurosurgery Department
🇮🇱Haifa, Israel
Polenov Neurosurgery Research Institute
🇷🇺St. Petersburg, Russian Federation
Omsk State Medical Academy; State Educational Institution of Higher Professional Education
🇷🇺Omsk, Russian Federation
Tcheliabinsk Regional Clinical Hospital; State Medical Institution for Prophylaxis and Treatment
🇷🇺Tcheliabinsk, Russian Federation
Sree Chitra Tirunal Institute for Medical Sciences & Technology, Department of Neurosurgery
🇮🇳Trivandrum, Kerala, India
Soroka Medical Center, Neurosurgery Department
🇮🇱Beer Sheva, Israel
Landes-Nervenklinik Wagner-Jauregg
🇦🇹Linz, Austria
Department of Neurosurgery, National Institute of Mental Health and Neurosciences
🇮🇳Bangalore, India
Military Medical Academy named after I.S.M. Kirov, Neurosurgery Department
🇷🇺St. Petersburg, Russian Federation
Department of Neurosurgery, Amrita Institute of Medical Sciences & Research Centre
🇮🇳Cochin, Kerala, India
Republican Clinical Hospital of Ministry of Health of Tatarstan Republic
🇷🇺Kazan, Russian Federation
Sarajishvili Institute of Clinical Neurology and Neurosurgery
🇬🇪Tbilisi, Georgia
Department of Neurosurgery, Neurosciences Center
🇮🇳New Dehli, India
Department of Neurological Sciences, Christian Medical College & Hospital
🇮🇳Vellore, India
Rabin Medical Center, Neurosurgery Department
🇮🇱Petach Tikva, Israel
State Institution of Healthcare, Samara Regional Clinical Hospital in the name of M.I. Kalinin
🇷🇺Samara, Russian Federation
Medical Center "XXI century"
🇷🇺St. Petersburg, Russian Federation
Burdenko Neurosurgery Research Institute
🇷🇺Moscow, Russian Federation