APG101 in Glioblastoma

Phase 2

Completed

• Conditions: Glioblastoma Multiforme
• Interventions: Procedure: Blood drawing; Drug: APG101

• Registration Number: NCT01071837
• Lead Sponsor: Apogenix GmbH

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.

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 Timeline

• Study Start: 2009-12
• Study First Submitted: 2010-02-18
• Study First Submitted QC: 2010-02-18
• Study First Posted: 2010-02-19
• Primary Completion: 2014-10
• Study Completion: 2014-10
• Status Verified: 2015-06
• Last Update Submitted: 2015-06-15
• Last Update Posted: 2015-06-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 84

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Re-Irradiation	Blood drawing	33% of the patients will be randomized to reirradiation (RT) alone. They will receive 36 Gy (2 Gy per fraction)
Re-Irradiation + APG101	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

Primary Outcome Measures

Name	Time	Method
6 months rate of progression free survival (PFS6)	6 month

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (21)

Universitätsklinik Heidelberg, Abteilung Neuroonkologie; 🇩🇪 Heidelberg, Germany

Universitätsklinikum Tuebingen, Strahlenonkologie; 🇩🇪 Tuebingen, Germany

Charite Universitätsmedizin Berlin, Klinik für Neurochirugie; 🇩🇪 Berlin, Germany

Universität Leipzig, Klinik für Strahlentherapie; 🇩🇪 Leipzig, Germany

Uniklinik Ulm, Klinik für Strahlentherapie und Radioonkologie; 🇩🇪 Ulm, Germany

Neurologische Universitätsklinik am Knappschaftskrankenhaus; 🇩🇪 Bochum, Germany

Klinikum Stuttgart, Neurozentrum Neurochirurgie; 🇩🇪 Stuttgart, Germany

Neurologische Universitätsklinik Bonn, Schwerpunkt klinische Neuroonkologie; 🇩🇪 Bonn, Germany

Universitätsklinik für Neurologie, Landeskrankenhaus Innsbruck; 🇦🇹 Innsbruck, Austria

Landesnervenklinik Wagner-Jauregg, Innere Medizin mit Neuroonkologie; 🇦🇹 Linz, Austria

Medizinische Universität Graz, Universitätsklinik für Neurologie Landeskrankenhaus Graz; 🇦🇹 Graz, Austria

Allgemeines Krankenhaus der Stadt Wien, Klinische Onkologie; 🇦🇹 Wien, Austria

Universitätsklinik Dresden, Klinik und Poliklinik für Neurochirurgie; 🇩🇪 Dresden, Germany

Universitätsmedizin Mannheim, Klinik für Neurochirurgie; 🇩🇪 Mannheim, Germany

Universitätsklinik Hamburg, Klinik für Neurochirugie; 🇩🇪 Hamburg, Germany

Philipps-Universität Marburg, Klinik für Neurologie; 🇩🇪 Marburg, Germany

LMU München, Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Campus Großhadern & Campus Innenstadt; 🇩🇪 München, Germany

Klinikum Frankfurt/Oder, Klinik für Strahlentherapie/Radioonkologie; 🇩🇪 Frankfurt/Oder, Germany

Städt. Kliniken München GmbH, Klinikum Bogenhausen, Abt. Neurochirurgie; 🇩🇪 München, Germany

Klinik und Poliklinik für Strahlentherapie/Radiologische Onkologie, Klinikum rechts der Isar, TU München; 🇩🇪 München, Germany

Klinik und Poliklinik der Universität Regensburg, Im Bezirksklinikum; 🇩🇪 Regensburg, Germany