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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:
Antisense Pharma
ClinicalTrials.gov Identifier:
NCT00431561
First received: February 5, 2007
Last updated: December 3, 2009
Last verified: December 2009
History of Changes
  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:

MedlinePlus related topics: Cancer
U.S. FDA Resources

Further study details as provided by Antisense Pharma:

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

Sponsors and Collaborators
Antisense Pharma
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 3, 2009
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 Antisense Pharma:
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 May 19, 2013