APG101 in Glioblastoma

Sponsor

Apogenix GmbH (Industry)

Overall Status

Completed

CT.gov ID

NCT01071837

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Glioblastoma Multiforme	Drug: APG101 Procedure: Blood drawing	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

84 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Dec 1, 2009

Actual Primary Completion Date :

Oct 1, 2014

Actual Study Completion Date :

Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
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)
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 Names: Recombinant fusion protein

Arm

Intervention/Treatment

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)

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 Names:

Recombinant fusion protein

Outcome Measures

Primary Outcome Measures

6 months rate of progression free survival (PFS6) [6 month]

Secondary Outcome Measures

Safety and tolerability of APG101 [ongoing during study]
Progression-free survival [until progression of underlying disease]
Objective response rates (OR) [ongoing during study]
Duration of response (DR) in responders [ongoing during study]
Overall survival [until study and after end of study (by 8-weekly phone calls)]
Quality of life [ongoing during study]
Cognitive function [ongoing during study]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	Country	Postal Code
1	Medizinische Universität Graz, Universitätsklinik für Neurologie Landeskrankenhaus Graz	Graz	Austria	8036
2	Universitätsklinik für Neurologie, Landeskrankenhaus Innsbruck	Innsbruck	Austria	6020
3	Landesnervenklinik Wagner-Jauregg, Innere Medizin mit Neuroonkologie	Linz	Austria	4020
4	Allgemeines Krankenhaus der Stadt Wien, Klinische Onkologie	Wien	Austria	1090
5	Charite Universitätsmedizin Berlin, Klinik für Neurochirugie	Berlin	Germany	13353
6	Neurologische Universitätsklinik am Knappschaftskrankenhaus	Bochum	Germany	44892
7	Neurologische Universitätsklinik Bonn, Schwerpunkt klinische Neuroonkologie	Bonn	Germany	53105
8	Universitätsklinik Dresden, Klinik und Poliklinik für Neurochirurgie	Dresden	Germany	01307
9	Klinikum Frankfurt/Oder, Klinik für Strahlentherapie/Radioonkologie	Frankfurt/Oder	Germany	15236
10	Universitätsklinik Hamburg, Klinik für Neurochirugie	Hamburg	Germany	20246
11	Universitätsklinik Heidelberg, Abteilung Neuroonkologie	Heidelberg	Germany	69120
12	Universität Leipzig, Klinik für Strahlentherapie	Leipzig	Germany	04103
13	Universitätsmedizin Mannheim, Klinik für Neurochirurgie	Mannheim	Germany	68167
14	Philipps-Universität Marburg, Klinik für Neurologie	Marburg	Germany	35039
15	LMU München, Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Campus Großhadern & Campus Innenstadt	München	Germany	81377
16	Klinik und Poliklinik für Strahlentherapie/Radiologische Onkologie, Klinikum rechts der Isar, TU München	München	Germany	81675
17	Städt. Kliniken München GmbH, Klinikum Bogenhausen, Abt. Neurochirurgie	München	Germany	81925
18	Klinik und Poliklinik der Universität Regensburg, Im Bezirksklinikum	Regensburg	Germany	93053
19	Klinikum Stuttgart, Neurozentrum Neurochirurgie	Stuttgart	Germany	70174
20	Universitätsklinikum Tuebingen, Strahlenonkologie	Tuebingen	Germany	72076
21	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Apogenix GmbH

ClinicalTrials.gov Identifier:

NCT01071837

Other Study ID Numbers:

APG101_CD_002

First Posted:

Feb 19, 2010

Last Update Posted:

Jun 16, 2015

Last Verified:

Jun 1, 2015

Keywords provided by Apogenix GmbH

Glioblastoma Multiforme

Additional relevant MeSH terms:

Glioblastoma

Study Results

No Results Posted as of Jun 16, 2015