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

NCT00431561 | Completed Phase 2 DMC

• 1 other identifier: AP 12009-G004
• Study Type: interventional
• Target: 141
• Locations: 6 countries
• Sites: 36

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.

Conditions

Glioblastoma; Anaplastic Astrocytoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Overall response rate of two AP 12009 dose groups and control group assessed by the evaluation of tumor size on brain MRI scans

Secondary Outcomes (10)

• Overall survival

  overall

• 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

Study Arms (3)

AP 12009 10 µM

EXPERIMENTAL

Drug: AP 12009 10 µM; Device: Drug delivery system for administration of AP 12009; Procedure: Placement of Drug Delivery System

AP 12009 80 µM

EXPERIMENTAL

Drug: AP 12009 80 µM; Device: Drug delivery system for administration of AP 12009; Procedure: Placement of Drug Delivery System

Chemotherapy

ACTIVE COMPARATOR

Drug: temozolomide or PCV

Interventions

AP 12009 10 µM DRUG

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

AP 12009 10 µM

AP 12009 80 µM DRUG

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

AP 12009 80 µM

temozolomide or PCV DRUG

temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle; PCV (procarbazine, CCNU, vincristine): standard regimen

Also known as: Temodar, Temodal, TMZ, lomustine, Cecenu, CeeNU

Chemotherapy

Drug delivery system for administration of AP 12009 DEVICE

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.

AP 12009 10 µM; AP 12009 80 µM

Placement of Drug Delivery System PROCEDURE

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; AP 12009 80 µM

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Isarna Therapeutics GmbH: lead

Study Sites (36)

Universitätsklinik Innsbruck; Abteilung für Neurochirurgie

Innsbruck, 6020, Austria

Location

Landes-Nervenklinik Wagner-Jauregg

Linz, 4020, Austria

Location

Kaiser Franz Josef Spital, Abteilung für Neurologie

Vienna, 1100, Austria

Location

Sarajishvili Institute of Clinical Neurology and Neurosurgery

Tbilisi, 0114, Georgia

Location

Medizinische Klinik und Poliklinik mit Schwerpunkt Onkologie und Hämatologie, Charité Campus Mitte

Berlin, 10117, Germany

Location

Klinik und Poliklinik für Neurologie

Cottbus, 03048, Germany

Location

Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

Dresden, 01307, Germany

Location

Universitätsklinikum Gießen, Neurochirurgische Universitätsklinik

Giessen, 35392, Germany

Location

Universitätsklinikum Kiel, Klinik für Neurochirurgie

Kiel, 24106, Germany

Location

Universitätsklinikum Leipzig, Klinik und Poliklinik für Neurochirurgie

Leipzig, 04103, Germany

Location

Universitätsklinik Magdeburg, Klinik für Neurochirurgie

Magdeburg, 39120, Germany

Location

Universitätskliniken Mainz, Neurochirurgische Klinik und Poliklinik

Mainz, 55131, Germany

Location

Universitätsklinikum Münster, Klinik und Poliklinik für Neurochirurgie

Münster, 48149, Germany

Location

Klinikum und Poliklinik für Neurologie, Universität Regensburg

Regensburg, 93053, Germany

Location

Klinikum Saarbrücken, Neurochirurgie

Saarbrücken, 66119, Germany

Location

Neurologische Universitätsklinik Tübingen

Tübingen, 72076, Germany

Location

Department of Neurosurgery, Amrita Institute of Medical Sciences & Research Centre

Kochi, Kerala, 682026, India

Location

Sree Chitra Tirunal Institute for Medical Sciences & Technology, Department of Neurosurgery

Trivandrum, Kerala, 695011, India

Location

Manipal Hospital; Manipal Institute for Neurological Disorders

Bangalore, 560017, India

Location

Department of Neurosurgery, National Institute of Mental Health and Neurosciences

Bangalore, 560029, India

Location

Department of Medical Oncology, Nizam's Institute of Medical Sciences

Hyderabad, 500082, India

Location

Department of Neurosurgery, LTMG Hospital & LTM Medical College

Mumbai, 400022, India

Location

Department of Neurosurgery, Neurosciences Center

New Dehli, 110029, India

Location

Department of Neurological Sciences, Christian Medical College & Hospital

Vellore, 632004, India

Location

Soroka Medical Center, Neurosurgery Department

Beersheba, Israel

Location

Rambam Medical Center, Neurosurgery Department

Haifa, 31096, Israel

Location

Rabin Medical Center, Neurosurgery Department

Petah Tikva, 49100, Israel

Location

Tcheliabinsk Regional Clinical Hospital; State Medical Institution for Prophylaxis and Treatment

Chelyabinsk, 454076, Russia

Location

Republican Clinical Hospital of Ministry of Health of Tatarstan Republic

Kazan', 420064, Russia

Location

Burdenko Neurosurgery Research Institute

Moscow, 125047, Russia

Location

Omsk State Medical Academy; State Educational Institution of Higher Professional Education

Omsk, 644099, Russia

Location

Polenov Neurosurgery Research Institute

Saint Petersburg, 191104, Russia

Location

Military Medical Academy named after I.S.M. Kirov, Neurosurgery Department

Saint Petersburg, 194175, Russia

Location

Medical Center "XXI century"

Saint Petersburg, 194354, Russia

Location

State Institution of Healthcare, Samara Regional Clinical Hospital in the name of M.I. Kalinin

Samara, 443095, Russia

Location

Sverdlovsk Regional Oncological Clinic

Yekaterinburg, 620036, Russia

Location

Related Publications (1)

• Uckun FM, Qazi S, Hwang L, Trieu VN. Recurrent or Refractory High-Grade Gliomas Treated by Convection-Enhanced Delivery of a TGFbeta2-Targeting RNA Therapeutic: A Post-Hoc Analysis with Long-Term Follow-Up. Cancers (Basel). 2019 Nov 28;11(12):1892. doi: 10.3390/cancers11121892.

  PMID: 31795071 DERIVED

MeSH Terms

Conditions

Glioblastoma; Astrocytoma; Neoplasms; Brain Neoplasms; Camurati-Engelmann Syndrome

Interventions

Trabedersen; Temozolomide; Lomustine; Drug Delivery Systems

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Drug Therapy; Therapeutics

Study Officials

• Ulrich Bogdahn, MD

  University of Regensburg, Dept. of Neurology, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: February 5, 2007
• First Posted: February 6, 2007
• Study Start: April 1, 2003
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: December 3, 2013

Record last verified: 2013-12

Locations

RU (9); AU (3); DE (12); IN (8); GE (1); IL (3)