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

Phase 2

Completed

• Conditions: Glioblastoma; Anaplastic Astrocytoma
• Interventions: Drug: AP 12009 80 µM; Drug: temozolomide or PCV; Drug: AP 12009 10 µM; Device: Drug delivery system for administration of AP 12009; Procedure: 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.

Study Timeline

• Study Start: 2003-04
• Study First Submitted: 2007-02-05
• Study First Submitted QC: 2007-02-05
• Study First Posted: 2007-02-06
• Primary Completion: 2009-03
• Study Completion: 2009-03
• Status Verified: 2013-12
• Last Update Submitted: 2013-12-02
• Last Update Posted: 2013-12-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 141

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 & 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)

Universitätsklinik Innsbruck; Abteilung für Neurochirurgie; 🇦🇹 Innsbruck, Austria

Landes-Nervenklinik Wagner-Jauregg; 🇦🇹 Linz, Austria

Kaiser Franz Josef Spital, Abteilung für Neurologie; 🇦🇹 Wien, Austria

Sarajishvili Institute of Clinical Neurology and Neurosurgery; 🇬🇪 Tbilisi, Georgia

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

Universitätsklinikum Gießen, Neurochirurgische Universitätsklinik; 🇩🇪 Gießen, Germany

Universitätsklinikum Kiel, Klinik für Neurochirurgie; 🇩🇪 Kiel, Germany

Universitätsklinikum Leipzig, Klinik und Poliklinik für Neurochirurgie; 🇩🇪 Leipzig, Germany

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