Phase IIb Clinical Trial With TGF-β2 Antisense Compound AP 12009 for Recurrent or Refractory High-Grade Glioma - Full Text View

Sponsored by:	Antisense Pharma
Information provided by:	Antisense Pharma
ClinicalTrials.gov Identifier:	NCT00431561

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 II

MedlinePlus related topics: Cancer

Drug Information available for: Vincristine sulfate Vincristine Temozolomide Lomustine Procarbazine hydrochloride Procarbazine AP 12009 Isoetharine Isoetharine hydrochloride Isoetharine mesylate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
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

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

Arms	Assigned Interventions
AP 12009 10 µM: Experimental	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.
AP 12009 80 µM: Experimental	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.
Chemotherapy: Active Comparator	Drug: temozolomide or PCV temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle; PCV (procarbazine, CCNU, vincristine): standard regimen

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

Responsible Party:	Antisense Pharma ( Hubert Heinrichs, MD, PhD, Chief Medical Officer )
Study ID Numbers:	AP 12009-G004
Study First Received:	February 5, 2007
Last Updated:	October 21, 2008
ClinicalTrials.gov Identifier:	NCT00431561
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

Study placed in the following topic categories:

Glioblastoma
Astrocytoma
Lomustine
Vincristine
Temozolomide
Recurrence
Brain Neoplasms

Signs and Symptoms
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Procarbazine
Glioma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

Neoplasms, Nerve Tissue
Antineoplastic Agents, Alkylating
Neoplasms, Neuroepithelial
Alkylating Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009