APG101 in Glioblastoma - Full Text View

Sponsor:	Apogenix GmbH
Information provided by (Responsible Party):	Apogenix GmbH
ClinicalTrials.gov Identifier:	NCT01071837

Purpose

This is a phase II study of APG101 + reirradiation (RT) versus reirradiation. Patients suffering from a malignant brain tumor called glioblastoma having a first or second progression can be included. They will be randomized to RT or RT + APG101.

APG101 is a fusion protein (similar to an antibody) and will be administered as a weekly infusion. Patients can stay in this study as long as they benefit from the participation (no fixed end).

In this trial, 30-35 sites in Germany, Austria and Russia take part.

Condition	Intervention	Phase
Glioblastoma Multiforme	Drug: APG101 Procedure: Blood drawing	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II, Randomized, Open-label, Multi-centre Study of Weekly APG101 + Reirradiation Versus Reirradiation in the Treatment of Patients With First or Second Progression of Glioblastoma

Further study details as provided by Apogenix GmbH:

Primary Outcome Measures:

6 months rate of progression free survival (PFS6) [ Time Frame: 6 month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety and tolerability of APG101 [ Time Frame: ongoing during study ] [ Designated as safety issue: No ]
Progression-free survival [ Time Frame: until progression of underlying disease ] [ Designated as safety issue: No ]
Objective response rates (OR) [ Time Frame: ongoing during study ] [ Designated as safety issue: No ]
Duration of response (DR) in responders [ Time Frame: ongoing during study ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: until study and after end of study (by 8-weekly phone calls) ] [ Designated as safety issue: No ]
Quality of life [ Time Frame: ongoing during study ] [ Designated as safety issue: No ]
Cognitive function [ Time Frame: ongoing during study ] [ Designated as safety issue: No ]

Estimated Enrollment:	83
Study Start Date:	December 2009
Estimated Study Completion Date:	March 2012
Estimated Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Re-Irradiation 33% of the patients will be randomized to reirradiation (RT) alone. They will receive 36 Gy (2 Gy per fraction)	Procedure: Blood drawing Blood drawings, e.g. for safety labs, abdominal ultrasound, ECG. Re-Irradiation is not considered a study procedure, but standard of care (inclusion criterion) Other Name: n.a.
Experimental: Re-Irradiation + APG101 66% of the patients will be randomized to reirradiation (RT) + 400 mg APG101 weekly. They will receive 36 Gy (2 Gy per fraction) and 400 mg APG101 weekly as an intravenous infusion	Drug: APG101 400mg weekly as intravenous infusion Other Name: Recombinant fusion protein

Detailed Description:

In this phase II trial, patients with a recurrence / progression of glioblastoma (first or second progression) either not being eligible for tumour resection or having macroscopic residual tumour after resection of the recurrence can be included (tumor size must 1-4 cm in T1-weighted MRI). They must be candidates for a re-irradiation and will then be randomized in a 1:2 ratio to re-irradiation alone or re-irradiation + 400mg APG101 as a weekly intravenous infusion.

Radiotherapy (RT) is considered standard of care and not a study procedure. As prior therapies, a first radiotherapy (maximal dose of 60 Gy; at least 8 months since the end of preirradiation), a prior surgery (at least for histology) and at least one Temozolomide-containing chemotherapy are mandatory; patients with prior treatment with bevacizumab, iodine seeds and/or brachytherapy are not eligible. The patients' steroid dose must be stable or decreasing upon inclusion.

The number of patients to be included in this study is up to 83 (depending on the statistical 2-step SIMON design).

Primary objective: 6 months rate of progression free survival (PFS6). Subjects can participate in this study as long as a clinical benefit is considered by the treating physician.

MRI tumour imaging will be carried out every 6 weeks.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male and female patients with a recurrence / progression of glioblastoma either not being eligible for tumour resection or having macroscopic residual tumour after resection of the recurrence
Diagnosis of glioblastoma must be proven histologically and progress must be documented by MRI. MRI images must not be older than 2 weeks before first dosing/start of RT
Not more than two prior therapy regimens including one or two resections, one or two chemotherapies of which one must have been TMZ-containing and one radiotherapy (RT) for the brain tumour
Previous irradiation therapy of the primary tumour with a maximal dose of 60 Gy; at least 8 months since the end of preirradiation
Candidate for reirradiation with recurrent tumour visible on MRI-T1 (Gd) and with the largest diameter measuring 1 cm to 4 cm
Informed consent
Age at least 18 years, smoking or non-smoking, of any ethnic origin
Karnofsky performance index (KPI) ≥ 60%
Neutrophile counts > 1500/μl / Platelet counts > 80.000/μl / Haemoglobin > 10 g/dl / Serum creatinine < 1.5-fold upper normal range / Bilirubin, AST or ALT < 2,5-fold upper normal range unless attributed to anticonvulsants / Alkaline phosphatase < 2,5-fold upper normal range
Adequate contraception
Stable or decreasing treatment with steroids within 5 days before treatment start

Exclusion Criteria:

More than one RT of brain, prior first radiotherapy with more than 60 Gy
Cumulative total dose on the optical chiasm >54 Gy for 2 Gy/fraction, α/β=2
Prior treatment with bevacizumab, iodine seeds and/or brachytherapy
Unable to undergo MRI
Past medical history of diseases with poor prognosis according to the judgement of the Investigator, e.g. severe coronary heart disease, severe diabetes, immune deficiency, residual deficits after stroke, severe mental retardation
HIV or hepatitis infection
Pregnancy or breast feeding
Treatment within any other clinical trial parallel to the treatment phase of the current study or within 30 days before inclusion
Known active coronary artery disease, significant cardiac arrhythmias or severe congestive heart failure (NYHA class III - IV)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01071837

Locations

Austria
Medizinische Universität Graz, Universitätsklinik für Neurologie Landeskrankenhaus Graz
Graz, Austria, 8036
Universitätsklinik für Neurologie, Landeskrankenhaus Innsbruck
Innsbruck, Austria, 6020
Landesnervenklinik Wagner-Jauregg, Innere Medizin mit Neuroonkologie
Linz, Austria, 4020
Allgemeines Krankenhaus der Stadt Wien, Klinische Onkologie
Wien, Austria, 1090
Germany
Charite Universitätsmedizin Berlin, Klinik für Neurochirugie
Berlin, Germany, 13353
Neurologische Universitätsklinik am Knappschaftskrankenhaus
Bochum, Germany, 44892
Neurologische Universitätsklinik Bonn, Schwerpunkt klinische Neuroonkologie
Bonn, Germany, 53105
Universitätsklinik Dresden, Klinik und Poliklinik für Neurochirurgie
Dresden, Germany, 01307
Klinikum Frankfurt/Oder, Klinik für Strahlentherapie/Radioonkologie
Frankfurt/Oder, Germany, 15236
Universitätsklinik Hamburg, Klinik für Neurochirugie
Hamburg, Germany, 20246
Universitätsklinik Heidelberg, Abteilung Neuroonkologie
Heidelberg, Germany, 69120
Universität Leipzig, Klinik für Strahlentherapie
Leipzig, Germany, 04103
Universitätsmedizin Mannheim, Klinik für Neurochirurgie
Mannheim, Germany, 68167
Philipps-Universität Marburg, Klinik für Neurologie
Marburg, Germany, 35039
LMU München, Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Campus Großhadern & Campus Innenstadt
München, Germany, 81377
Städt. Kliniken München GmbH, Klinikum Bogenhausen, Abt. Neurochirurgie
München, Germany, 81925
Klinik und Poliklinik für Strahlentherapie/Radiologische Onkologie, Klinikum rechts der Isar, TU München
München, Germany, 81675
Klinik und Poliklinik der Universität Regensburg, Im Bezirksklinikum
Regensburg, Germany, 93053
Klinikum Stuttgart, Neurozentrum Neurochirurgie
Stuttgart, Germany, 70174
Universitätsklinikum Tuebingen, Strahlenonkologie
Tuebingen, Germany, 72076
Uniklinik Ulm, Klinik für Strahlentherapie und Radioonkologie
Ulm, Germany, 89081

Sponsors and Collaborators

Apogenix GmbH

Investigators

Study Director:

Wolfgang Wick, MD

University Hospital Heidelberg, Dept. of Neurooncology, Germany

More Information

No publications provided

Responsible Party:	Apogenix GmbH
ClinicalTrials.gov Identifier:	NCT01071837 History of Changes
Other Study ID Numbers:	APG101_CD_002
Study First Received:	February 18, 2010
Last Updated:	September 12, 2011
Health Authority:	Germany: Paul-Ehrlich-Institut; Austria: Federal Office for Safety in Health Care; Austria: Agency for Health and Food Safety

Keywords provided by Apogenix GmbH:

Glioblastoma Multiforme

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

ClinicalTrials.gov processed this record on February 09, 2012