Trial | NCT00431561  Report issue

Title

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

  • Phase

    Phase 2

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Intervention/Treatment

    trabedersen temozolomide ...

  • Study Participants

    141
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 Started
Apr 30
2003
Primary Completion
Mar 31
2009
Study Completion
Mar 31
2009
Last Update
Dec 03
2013
Estimate

Drug AP 12009 10 µM

10 µM AP 12009 (trabedersen), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks

Drug AP 12009 80 µM

80 µM AP 12009 (trabedersen), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks

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

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.

AP 12009 10 µM Experimental

AP 12009 80 µM Experimental

Chemotherapy Active Comparator

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
No Results Posted