APG101 in Glioblastoma

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

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.

Study Overview

• Status: Completed
• Conditions: Glioblastoma Multiforme
• Intervention / Treatment: Procedure: Blood drawing; Drug: APG101

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 Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
6 months rate of progression free survival (PFS6)	6 month

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Apogenix GmbH
• Investigators: Study Director: Wolfgang Wick, MD, University Hospital Heidelberg, Dept. of Neurooncology, Germany

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: February 18, 2010
• First Submitted That Met QC Criteria: February 18, 2010
• First Posted (Estimate): February 19, 2010

Study Record Updates

• Last Update Posted (Estimate): June 16, 2015
• Last Update Submitted That Met QC Criteria: June 15, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Glioblastoma Multiforme
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: APG101_CD_002