APG101 in Glioblastoma

Glioblastoma Multiforme Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01071837
• Other study ID #: APG101_CD_002
• Status: Completed
• Phase: Phase 2
• First received: February 18, 2010
• Last updated: June 15, 2015
• Start date: December 2009
• Est. completion date: October 2014

Study information

• Verified date: June 2015
• Source: Apogenix GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-InstitutAustria: Federal Office for Safety in Health CareAustria: Agency for Health and Food Safety
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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, a/ß=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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

Drug:
• APG101
400mg weekly as intravenous infusion

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)

Locations

Country	Name	City	State
Austria	Medizinische Universität Graz, Universitätsklinik für Neurologie Landeskrankenhaus Graz	Graz
Austria	Universitätsklinik für Neurologie, Landeskrankenhaus Innsbruck	Innsbruck
Austria	Landesnervenklinik Wagner-Jauregg, Innere Medizin mit Neuroonkologie	Linz
Austria	Allgemeines Krankenhaus der Stadt Wien, Klinische Onkologie	Wien
Germany	Charite Universitätsmedizin Berlin, Klinik für Neurochirugie	Berlin
Germany	Neurologische Universitätsklinik am Knappschaftskrankenhaus	Bochum
Germany	Neurologische Universitätsklinik Bonn, Schwerpunkt klinische Neuroonkologie	Bonn
Germany	Universitätsklinik Dresden, Klinik und Poliklinik für Neurochirurgie	Dresden
Germany	Klinikum Frankfurt/Oder, Klinik für Strahlentherapie/Radioonkologie	Frankfurt/Oder
Germany	Universitätsklinik Hamburg, Klinik für Neurochirugie	Hamburg
Germany	Universitätsklinik Heidelberg, Abteilung Neuroonkologie	Heidelberg
Germany	Universität Leipzig, Klinik für Strahlentherapie	Leipzig
Germany	Universitätsmedizin Mannheim, Klinik für Neurochirurgie	Mannheim
Germany	Philipps-Universität Marburg, Klinik für Neurologie	Marburg
Germany	Klinik und Poliklinik für Strahlentherapie/Radiologische Onkologie, Klinikum rechts der Isar, TU München	München
Germany	LMU München, Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Campus Großhadern & Campus Innenstadt	München
Germany	Städt. Kliniken München GmbH, Klinikum Bogenhausen, Abt. Neurochirurgie	München
Germany	Klinik und Poliklinik der Universität Regensburg, Im Bezirksklinikum	Regensburg
Germany	Klinikum Stuttgart, Neurozentrum Neurochirurgie	Stuttgart
Germany	Universitätsklinikum Tuebingen, Strahlenonkologie	Tuebingen
Germany	Uniklinik Ulm, Klinik für Strahlentherapie und Radioonkologie	Ulm

Sponsors (1)

Lead Sponsor	Collaborator
Apogenix GmbH

Countries where clinical trial is conducted

Austria,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	6 months rate of progression free survival (PFS6)		6 month	No
Secondary	Safety and tolerability of APG101		ongoing during study	No
Secondary	Progression-free survival		until progression of underlying disease	No
Secondary	Objective response rates (OR)		ongoing during study	No
Secondary	Duration of response (DR) in responders		ongoing during study	No
Secondary	Overall survival		until study and after end of study (by 8-weekly phone calls)	No
Secondary	Quality of life		ongoing during study	No
Secondary	Cognitive function		ongoing during study	No