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

December 2, 2013 updated by: Isarna Therapeutics GmbH

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

141

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
  • CeeNU
  • Cecenu
  • lomustine
EXPERIMENTAL: AP 12009 10 µM
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.
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.
EXPERIMENTAL: AP 12009 80 µM
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.
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.
Drug: AP 12009 80 µM
80 µM AP 12009 (trabedersen), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

Outcome Measure
Time Frame
Time to progression
Safety and tolerability
Time to response
Overall survival
Time Frame: overall
overall
Overall survival
Time Frame: six- and twelve-month
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)
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
six-month
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)
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Isarna Therapeutics GmbH

Investigators

  • Principal Investigator: Ulrich Bogdahn, MD, University of Regensburg, Dept. of Neurology, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2003

Primary Completion (ACTUAL)

March 1, 2009

Study Completion (ACTUAL)

March 1, 2009

Study Registration Dates

First Submitted

February 5, 2007

First Submitted That Met QC Criteria

February 5, 2007

First Posted (ESTIMATE)

February 6, 2007

Study Record Updates

Last Update Posted (ESTIMATE)

December 3, 2013

Last Update Submitted That Met QC Criteria

December 2, 2013

Last Verified

December 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AP 12009-G004

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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