Dendritic Cell Cancer Vaccine for High-grade Glioma - Full Text View

Sponsor:	Trimed Biotech GmbH
Information provided by:	Trimed Biotech GmbH
ClinicalTrials.gov Identifier:	NCT01213407

Purpose

A randomised, open-label, 2-arm, multi-centre, phase II clinical study with one group receiving standard therapy with Temozolomide, radiotherapy, and Trivax; and a control group receiving standard therapy with Temozolomide and radiotherapy only; after tumour resection of at least 70% in both groups. The hypothesis is based on the assumption that time to progression will be doubled in the treatment group.

Condition	Intervention	Phase
Glioblastoma Multiforme	Drug: Trivax, Temozolomide, Surgery, Radiotherapy Drug: Temozolomide, Surgery, Radiotherapy	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	First Line Standard Therapy of Glioblastoma Multiforme With or Without add-on Treatment With Trivax, an Anti-tumour Immune Therapy Based on Tumour-lysate Charged Dendritic Cells

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Temozolomide Interleukin-12

U.S. FDA Resources

Further study details as provided by Trimed Biotech GmbH:

Primary Outcome Measures:

Progression free survival [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Progression free survival measured as percentage of non-progressive patients with newly diagnosed GBM 12 months after a post-operative MRI scan treated according to the current standard (surgical resection, irradiation, oral chemotherapy with Temozolomide), and Trivax, an autologous DC cancer vaccine charged with autologous tumour protein, as add-on therapy (group A), in comparison to patients receiving standard treatment without Trivax (group B).

Secondary Outcome Measures:

Quality of Life [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
Quality of life in patients treated with Trivax as an add-on therapy using ECOG (Eastern Cooperative Oncology Group) performance status compared to quality of life of patients receiving standard therapy (for study patients older 18 years).
Progression free survival at 18 and 24 months [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
Progression free survival measured as percentage of non-progressive patients at 18 and 24 months post initiation of treat-ment.
Overall survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
The percentage of survival will be assessed at 12, 18, and 24 months.

Estimated Enrollment:	56
Study Start Date:	March 2010
Estimated Study Completion Date:	December 2012
Estimated Primary Completion Date:	March 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Standard therapy plus Trivax Standard therapy with Surgery, Temozolomide, and Radiotherapy; plus Trivax, 5x10e6 autologous interleukine-12 secreting dendritic cells charged with autologous tumour lysate.	Drug: Trivax, Temozolomide, Surgery, Radiotherapy Trivax: 5 x 10e6 dendritic cells, intranodal in 500 µl NaCl, weeks 7, 8, 9, 10, 12, 16, 20, 24, 28, 32 Irradiation: 2 Gy per fraction once daily, five days per week (Mo-Fr), weeks 1, 2, 3, 4, 5, 6, total dose 60 Gy Temozolomide concomitant to radiotherapy: 75 mg/m²/day, 5 days per week (Mo-Fr), weeks 1, 2, 3, 4, 5, 6. Break: weeks 7, 8, 9, 10. Temozolomide adjuvant: 150 mg/m²/day, five days per week (Mo-Fr), week 11; 200 mg/m²/day, five days per week (Mo-Fr), weeks 15, 19, 23, 27, 31. Other Name: Temodal
Active Comparator: Standard therapy Surgery, Temozolomide, Radiotherapy	Drug: Trivax, Temozolomide, Surgery, Radiotherapy Trivax: 5 x 10e6 dendritic cells, intranodal in 500 µl NaCl, weeks 7, 8, 9, 10, 12, 16, 20, 24, 28, 32 Irradiation: 2 Gy per fraction once daily, five days per week (Mo-Fr), weeks 1, 2, 3, 4, 5, 6, total dose 60 Gy Temozolomide concomitant to radiotherapy: 75 mg/m²/day, 5 days per week (Mo-Fr), weeks 1, 2, 3, 4, 5, 6. Break: weeks 7, 8, 9, 10. Temozolomide adjuvant: 150 mg/m²/day, five days per week (Mo-Fr), week 11; 200 mg/m²/day, five days per week (Mo-Fr), weeks 15, 19, 23, 27, 31. Other Name: Temodal Drug: Temozolomide, Surgery, Radiotherapy Irradiation: 2 Gy per fraction once daily, five days per week (Mo-Fr), weeks 1, 2, 3, 4, 5, 6, total dose 60 Gy Temozolomide concomitant to radiotherapy: 75 mg/m²/day, 5 days per week (Mo-Fr), weeks 1, 2, 3, 4, 5, 6 Break: weeks 7, 8, 9, 10 Temozolomide adjuvant: 150 mg/m²/day, five days per week (Mo-Fr), week 11; 200 mg/m²/day, five days per week (Mo-Fr), weeks 15, 19, 23, 27, 31 Other Name: Temodal

Arms

Assigned Interventions

Experimental: Standard therapy plus Trivax

Standard therapy with Surgery, Temozolomide, and Radiotherapy; plus Trivax, 5x10e6 autologous interleukine-12 secreting dendritic cells charged with autologous tumour lysate.

Drug: Trivax, Temozolomide, Surgery, Radiotherapy

Trivax: 5 x 10e6 dendritic cells, intranodal in 500 µl NaCl, weeks 7, 8, 9, 10, 12, 16, 20, 24, 28, 32

Irradiation: 2 Gy per fraction once daily, five days per week (Mo-Fr), weeks 1, 2, 3, 4, 5, 6, total dose 60 Gy

Temozolomide concomitant to radiotherapy: 75 mg/m²/day, 5 days per week (Mo-Fr), weeks 1, 2, 3, 4, 5, 6.

Break: weeks 7, 8, 9, 10.

Temozolomide adjuvant: 150 mg/m²/day, five days per week (Mo-Fr), week 11; 200 mg/m²/day, five days per week (Mo-Fr), weeks 15, 19, 23, 27, 31.

Other Name: Temodal

Active Comparator: Standard therapy

Surgery, Temozolomide, Radiotherapy

Drug: Trivax, Temozolomide, Surgery, Radiotherapy

Trivax: 5 x 10e6 dendritic cells, intranodal in 500 µl NaCl, weeks 7, 8, 9, 10, 12, 16, 20, 24, 28, 32

Irradiation: 2 Gy per fraction once daily, five days per week (Mo-Fr), weeks 1, 2, 3, 4, 5, 6, total dose 60 Gy

Temozolomide concomitant to radiotherapy: 75 mg/m²/day, 5 days per week (Mo-Fr), weeks 1, 2, 3, 4, 5, 6.

Break: weeks 7, 8, 9, 10.

Temozolomide adjuvant: 150 mg/m²/day, five days per week (Mo-Fr), week 11; 200 mg/m²/day, five days per week (Mo-Fr), weeks 15, 19, 23, 27, 31.

Other Name: Temodal

Drug: Temozolomide, Surgery, Radiotherapy

Irradiation: 2 Gy per fraction once daily, five days per week (Mo-Fr), weeks 1, 2, 3, 4, 5, 6, total dose 60 Gy

Temozolomide concomitant to radiotherapy: 75 mg/m²/day, 5 days per week (Mo-Fr), weeks 1, 2, 3, 4, 5, 6

Break: weeks 7, 8, 9, 10

Temozolomide adjuvant: 150 mg/m²/day, five days per week (Mo-Fr), week 11; 200 mg/m²/day, five days per week (Mo-Fr), weeks 15, 19, 23, 27, 31

Other Name: Temodal

Show Detailed Description

Eligibility

Ages Eligible for Study:	3 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Female or male, paediatric or adult patients of 3 to 70 years of age at time of diagnosis that qualify for standard treatment including surgery, Temozolomide and radiotherapy.
GBM (WHO IV), confirmed by histology.
Total, subtotal, or partial resection of more then 70% of tumour mass defined by MRI.
Supratentorial tumour localisation.
ECOG performance status 0, 1, or 2 (for study patients older 18 years).
Life expectancy of at least 12 weeks by assessment of the attending physician.
Written informed consent of patient and/or legal guardian in case of children or adolescents.

Exclusion Criteria:

Less than 100 µg of tumour protein obtained from the resected tissue.
Anti-neoplastic chemotherapy or radiotherapy during 4 weeks before entering the study, e.g. in another therapeutic phase I, II, or III study.
Positive pregnancy test or breast-feeding.
Patients unwilling to perform a save method of birth control.
Known hypersensitivity to temozolomide.
HIV positivity.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01213407

Contacts

Contact: Thomas Felzmann, MD, MBA

+431 40170 ext 4080

thomas.felzmann@ccri.at

Locations

Austria
Landesnervenklinik Wagner-Jauregg	Recruiting
Linz, Oberösterreich, Austria, 4020
Contact: Johanna Buchroithner, MD +43 (0)50 554/62 ext 25921 johanna.buchroithner@gespag.at
Contact: Josef Pichler, MD +43 (0)50 554/62 ext 28556 interneambulanz.wj@gespag.at
Principal Investigator: Johanna Buchroithner, MD
Landeskrankenhaus Feldkirch	Recruiting
Feldkirch, Austria, 6807
Contact: Karl Roessler, MD +43 5522 / 303 ext 1901 karl.roessler@lkhf.at
Principal Investigator: Karl Rössler, MD
Medical University Innsbruck	Recruiting
Innsbruck, Austria, 6020
Contact: Günther Stockhammer, MD +43-512-504 ext 24368 guenther.stockhammer@i-med.ac.at
Principal Investigator: Günther Stockhammer, MD
Kaiser Franz-Josef Spital	Recruiting
Vienna, Austria, 1100
Contact: Stefan Oberndorfer, MD +431 601 91 ext 2061 stefan.oberndorfer@wienkav.at
Contact: Günther Kleinpeter, MD +431 711 65 ext 4301 guenther.kleinpeter@wienkav.at
Principal Investigator: Stefan Oberndorfer, MD
Donauspital, SMZ-Ost	Recruiting
Vienna, Austria, 1220
Contact: Reinhard Ruckser, MD +431 288 02 ext 3214 reinhard.ruckser@wienkav.at
Contact: Elvira Kitzweger +431 288 02 ext 3280 elvira.kitzweger@wienkav.at
Principal Investigator: Reinhard Ruckser, MD
Medical University Vienna	Recruiting
Vienna, Austria, 1090
Contact: Christine Marosi, MD +431 40400 ext 4447 christine.marosi@meduniwien.ac.at
Contact: Cornelia Sax, MSc +431 40400 ext 4421 cornelia.sax@meduniwien.ac.at
Principal Investigator: Christine Marosi, MD

Sponsors and Collaborators

Trimed Biotech GmbH

Investigators

Principal Investigator:

Johanna Buchroithner, MD

Landesnervenklinik Wagner-Jauregg

More Information

Additional Information:

St. Anna Children's Cancer Research Institute This link exits the ClinicalTrials.gov site

Central European Society for Anticancer Drug Research This link exits the ClinicalTrials.gov site

Medical University Vienna This link exits the ClinicalTrials.gov site

Publications:

Dohnal AM, Graffi S, Witt V, Eichstill C, Wagner D, Ul-Haq S, Wimmer D, Felzmann T. Comparative evaluation of techniques for the manufacturing of dendritic cell-based cancer vaccines. J Cell Mol Med. 2009 Jan;13(1):125-35. Epub 2008 Mar 17.

Dohnal AM, Witt V, Hügel H, Holter W, Gadner H, Felzmann T. Phase I study of tumor Ag-loaded IL-12 secreting semi-mature DC for the treatment of pediatric cancer. Cytotherapy. 2007;9(8):755-70. Epub 2007 Oct 4.

Felzmann T, Hüttner KG, Breuer SK, Wimmer D, Ressmann G, Wagner D, Paul P, Lehner M, Heitger A, Holter W. Semi-mature IL-12 secreting dendritic cells present exogenous antigen to trigger cytolytic immune responses. Cancer Immunol Immunother. 2005 Aug;54(8):769-80. Epub 2005 Jan 13.

Hüttner KG, Breuer SK, Paul P, Majdic O, Heitger A, Felzmann T. Generation of potent anti-tumor immunity in mice by interleukin-12-secreting dendritic cells. Cancer Immunol Immunother. 2005 Jan;54(1):67-77.

Dohnal AM, Luger R, Paul P, Fuchs D, Felzmann T. CD40 ligation restores type 1 polarizing capacity in TLR4-activated dendritic cells that have ceased interleukin-12 expression. J Cell Mol Med. 2009 Aug;13(8B):1741-50.

Traxlmayr MW, Wesch D, Dohnal AM, Funovics P, Fischer MB, Kabelitz D, Felzmann T. Immune suppression by gammadelta T-cells as a potential regulatory mechanism after cancer vaccination with IL-12 secreting dendritic cells. J Immunother. 2010 Jan;33(1):40-52.

Responsible Party:	Thomas Felzmann, Trimed Biotech GmbH
ClinicalTrials.gov Identifier:	NCT01213407 History of Changes
Other Study ID Numbers:	GBM-Vax
Study First Received:	May 28, 2010
Last Updated:	October 1, 2010
Health Authority:	Austria: Agency for Health and Food Safety

Keywords provided by Trimed Biotech GmbH:

Dendritic cell
Cancer vaccine
Anti-tumor immune therapy
Interleukine-12
Individualised autologous therapy
Brain cancer
Temozolomide
Radiotherapy
Irradiation
High-grade glioma
Advanced therapy medicinal product ATMP
Somatic cell therapy

Leukocyte apheresis
Neurosurgery
Neurooncology
Neurology
Immunology
Tumor immunology
Transfusion medicine
Monocyte
Killer cell
Cytotoxic T-cell
Cytotoxic T-lymphocyte

Additional relevant MeSH terms:

Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Interleukin-12

Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Adjuvants, Immunologic
Immunologic Factors

ClinicalTrials.gov processed this record on May 23, 2012