APG101 in Glioblastoma

NCT01071837 | Completed Phase 2 DMC

• 1 other identifier: APG101_CD_002
• Study Type: interventional
• Target: 84
• Locations: 2 countries
• Sites: 21

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.

Conditions

Glioblastoma Multiforme

Keywords

Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (1)

• 6 months rate of progression free survival (PFS6)

  6 month

Secondary Outcomes (7)

• 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)

Study Arms (2)

Re-Irradiation

ACTIVE COMPARATOR

33% of the patients will be randomized to reirradiation (RT) alone. They will receive 36 Gy (2 Gy per fraction)

Procedure: Blood drawing

Re-Irradiation + APG101

EXPERIMENTAL

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

Interventions

APG101 DRUG

400mg weekly as intravenous infusion

Also known as: Recombinant fusion protein

Re-Irradiation + APG101

Blood drawing PROCEDURE

Blood drawings, e.g. for safety labs, abdominal ultrasound, ECG. Re-Irradiation is not considered a study procedure, but standard of care (inclusion criterion)

Re-Irradiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Known active coronary artery disease, significant cardiac arrhythmias or severe congestive heart failure (NYHA class III - IV)

Sponsors & Collaborators

• Apogenix GmbH: lead

Study Sites (21)

Medizinische Universität Graz, Universitätsklinik für Neurologie Landeskrankenhaus Graz

Graz, 8036, Austria

Location

Universitätsklinik für Neurologie, Landeskrankenhaus Innsbruck

Innsbruck, 6020, Austria

Location

Landesnervenklinik Wagner-Jauregg, Innere Medizin mit Neuroonkologie

Linz, 4020, Austria

Location

Allgemeines Krankenhaus der Stadt Wien, Klinische Onkologie

Vienna, 1090, Austria

Location

Charite Universitätsmedizin Berlin, Klinik für Neurochirugie

Berlin, 13353, Germany

Location

Neurologische Universitätsklinik am Knappschaftskrankenhaus

Bochum, 44892, Germany

Location

Neurologische Universitätsklinik Bonn, Schwerpunkt klinische Neuroonkologie

Bonn, 53105, Germany

Location

Universitätsklinik Dresden, Klinik und Poliklinik für Neurochirurgie

Dresden, 01307, Germany

Location

Klinikum Frankfurt/Oder, Klinik für Strahlentherapie/Radioonkologie

Frankfurt (Oder), 15236, Germany

Location

Universitätsklinik Hamburg, Klinik für Neurochirugie

Hamburg, 20246, Germany

Location

Universitätsklinik Heidelberg, Abteilung Neuroonkologie

Heidelberg, 69120, Germany

Location

Universität Leipzig, Klinik für Strahlentherapie

Leipzig, 04103, Germany

Location

Universitätsmedizin Mannheim, Klinik für Neurochirurgie

Mannheim, 68167, Germany

Location

Philipps-Universität Marburg, Klinik für Neurologie

Marburg, 35039, Germany

Location

LMU München, Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Campus Großhadern & Campus Innenstadt

München, 81377, Germany

Location

Klinik und Poliklinik für Strahlentherapie/Radiologische Onkologie, Klinikum rechts der Isar, TU München

München, 81675, Germany

Location

Städt. Kliniken München GmbH, Klinikum Bogenhausen, Abt. Neurochirurgie

München, 81925, Germany

Location

Klinik und Poliklinik der Universität Regensburg, Im Bezirksklinikum

Regensburg, 93053, Germany

Location

Klinikum Stuttgart, Neurozentrum Neurochirurgie

Stuttgart, 70174, Germany

Location

Universitätsklinikum Tuebingen, Strahlenonkologie

Tübingen, 72076, Germany

Location

Uniklinik Ulm, Klinik für Strahlentherapie und Radioonkologie

Ulm, 89081, Germany

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

APG101; Recombinant Fusion Proteins; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Wolfgang Wick, MD

  University Hospital Heidelberg, Dept. of Neurooncology, Germany

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2010
• First Posted: February 19, 2010
• Study Start: December 1, 2009
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: June 16, 2015

Record last verified: 2015-06

Locations

AU (4); DE (17)