Phase IIb Clinical Trial With TGF-β2 Antisense Compound AP 12009 for Recurrent or Refractory High-grade Glioma

This study has been completed.
Sponsor:
Information provided by:
Isarna Therapeutics GmbH
ClinicalTrials.gov Identifier:
NCT00431561
First received: February 5, 2007
Last updated: December 2, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Glioblastoma
Anaplastic Astrocytoma
Drug: AP 12009 10 µM
Drug: AP 12009 80 µM
Drug: temozolomide or PCV
Device: Drug delivery system for administration of AP 12009
Procedure: Placement of Drug Delivery System
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multi-national, Open-label, Active-controlled, Randomized Dose-finding Study to Evaluate Efficacy of 2 Doses of AP 12009 in Recurrent Glioma, Administered Intratumorally as Continuous High-flow Microperfusion Over 7 Days Every Other Week

Resource links provided by NLM:


Further study details as provided by Isarna Therapeutics GmbH:

Primary Outcome Measures:
  • Overall response rate of two AP 12009 dose groups and control group assessed by the evaluation of tumor size on brain MRI scans [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: overall ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: six- and twelve-month ] [ Designated as safety issue: No ]
  • Response rates [ Time Frame: at 3, 8, 10, and 12 months (and during the prolonged follow-up period in six-monthly intervals, if applicable) ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: six-month ] [ Designated as safety issue: No ]
  • Time to progression [ Designated as safety issue: No ]
  • Time to response [ Designated as safety issue: No ]
  • Best of all response rates assessed by survival status and variation of tumor size on brain MRI [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Best of all response rates [ Designated as safety issue: No ]
  • Safety and tolerability [ Designated as safety issue: Yes ]

Enrollment: 141
Study Start Date: April 2003
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AP 12009 10 µM Drug: AP 12009 10 µM
10 µM AP 12009 (trabedersen), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks
Device: Drug delivery system for administration of AP 12009
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.
Procedure: Placement of Drug Delivery System
Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.
Experimental: AP 12009 80 µM Drug: AP 12009 80 µM
80 µM AP 12009 (trabedersen), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks
Device: Drug delivery system for administration of AP 12009
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.
Procedure: Placement of Drug Delivery System
Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.
Active Comparator: Chemotherapy Drug: temozolomide or PCV
temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle; PCV (procarbazine, CCNU, vincristine): standard regimen
Other Names:
  • Temodar
  • Temodal
  • TMZ
  • lomustine
  • Cecenu
  • CeeNU

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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%

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00431561

Locations
Austria
Universitätsklinik Innsbruck; Abteilung für Neurochirurgie
Innsbruck, Austria, 6020
Landes-Nervenklinik Wagner-Jauregg
Linz, Austria, 4020
Kaiser Franz Josef Spital, Abteilung für Neurologie
Wien, Austria, 1100
Georgia
Sarajishvili Institute of Clinical Neurology and Neurosurgery
Tbilisi, Georgia, 0114
Germany
Medizinische Klinik und Poliklinik mit Schwerpunkt Onkologie und Hämatologie, Charité Campus Mitte
Berlin, Germany, 10117
Klinik und Poliklinik für Neurologie
Cottbus, Germany, 03048
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
Dresden, Germany, 01307
Universitätsklinikum Gießen, Neurochirurgische Universitätsklinik
Gießen, Germany, 35392
Universitätsklinikum Kiel, Klinik für Neurochirurgie
Kiel, Germany, 24106
Universitätsklinikum Leipzig, Klinik und Poliklinik für Neurochirurgie
Leipzig, Germany, 04103
Universitätsklinik Magdeburg, Klinik für Neurochirurgie
Magdeburg, Germany, 39120
Universitätskliniken Mainz, Neurochirurgische Klinik und Poliklinik
Mainz, Germany, 55131
Universitätsklinikum Münster, Klinik und Poliklinik für Neurochirurgie
Münster, Germany, 48149
Klinikum und Poliklinik für Neurologie, Universität Regensburg
Regensburg, Germany, 93053
Klinikum Saarbrücken, Neurochirurgie
Saarbrücken, Germany, 66119
Neurologische Universitätsklinik Tübingen
Tübingen, Germany, 72076
India
Department of Neurosurgery, Amrita Institute of Medical Sciences & Research Centre
Cochin, Kerala, India, 682026
Sree Chitra Tirunal Institute for Medical Sciences & Technology, Department of Neurosurgery
Trivandrum, Kerala, India, 695011
Manipal Hospital; Manipal Institute for Neurological Disorders
Bangalore, India, 560017
Department of Neurosurgery, National Institute of Mental Health and Neurosciences
Bangalore, India, 560029
Department of Medical Oncology, Nizam's Institute of Medical Sciences
Hyderabad, India, 500082
Department of Neurosurgery, LTMG Hospital & LTM Medical College
Mumbai, India, 400022
Department of Neurosurgery, Neurosciences Center
New Dehli, India, 110029
Department of Neurological Sciences, Christian Medical College & Hospital
Vellore, India, 632004
Israel
Soroka Medical Center, Neurosurgery Department
Beer Sheva, Israel
Rambam Medical Center, Neurosurgery Department
Haifa, Israel, 31096
Rabin Medical Center, Neurosurgery Department
Petach Tikva, Israel, 49100
Russian Federation
Sverdlovsk Regional Oncological Clinic
Ekaterinburg, Russian Federation, 620036
Republican Clinical Hospital of Ministry of Health of Tatarstan Republic
Kazan, Russian Federation, 420064
Burdenko Neurosurgery Research Institute
Moscow, Russian Federation, 125047
Omsk State Medical Academy; State Educational Institution of Higher Professional Education
Omsk, Russian Federation, 644099
State Institution of Healthcare, Samara Regional Clinical Hospital in the name of M.I. Kalinin
Samara, Russian Federation, 443095
Military Medical Academy named after I.S.M. Kirov, Neurosurgery Department
St. Petersburg, Russian Federation, 194175
Medical Center "XXI century"
St. Petersburg, Russian Federation, 194354
Polenov Neurosurgery Research Institute
St. Petersburg, Russian Federation, 191104
Tcheliabinsk Regional Clinical Hospital; State Medical Institution for Prophylaxis and Treatment
Tcheliabinsk, Russian Federation, 454076
Sponsors and Collaborators
Isarna Therapeutics GmbH
Investigators
Principal Investigator: Ulrich Bogdahn, MD University of Regensburg, Dept. of Neurology, Germany
  More Information

No publications provided

Responsible Party: Hubert Heinrichs, MD, PhD, Chief Medical Officer, Antisense Pharma
ClinicalTrials.gov Identifier: NCT00431561     History of Changes
Other Study ID Numbers: AP 12009-G004
Study First Received: February 5, 2007
Last Updated: December 2, 2013
Health Authority: Austria: Federal Ministry for Health and Women
Georgia: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
India: Ministry of Health
Israel: Ministry of Health
Russia: Pharmacological Committee, Ministry of Health

Keywords provided by Isarna Therapeutics GmbH:
Glioblastoma
Anaplastic astrocytoma
Antisense
Cancer
Transforming growth factor beta2 (TGF-beta2)
Targeted therapy
Immunotherapy
Brain tumor
Central nervous system (CNS)
Convection-enhanced delivery (CED) / microperfusion
Locoregional application

Additional relevant MeSH terms:
Astrocytoma
Glioblastoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Trabedersen
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014