APG101 in Glioblastoma

NCT ID: NCT01071837

Last Updated: 2015-06-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2014-10-31

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.

Conditions

Glioblastoma Multiforme

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Re-Irradiation

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

Group Type: ACTIVE_COMPARATOR

Blood drawing

Intervention Type: 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 + 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

Group Type: EXPERIMENTAL

APG101

Intervention Type: DRUG

400mg weekly as intravenous infusion

Interventions

APG101

400mg weekly as intravenous infusion

Intervention Type: DRUG

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)

Intervention Type: PROCEDURE

Other Intervention Names

Recombinant fusion protein

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Apogenix GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wolfgang Wick, MD

Role: STUDY_DIRECTOR

University Hospital Heidelberg, Dept. of Neurooncology, Germany

Locations

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

Vienna, , Austria

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

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

München, , Germany

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

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

Tübingen, , Germany

Uniklinik Ulm, Klinik für Strahlentherapie und Radioonkologie

Ulm, , Germany

Countries

Austria; Germany

Other Identifiers

APG101_CD_002

Identifier Type: -

Identifier Source: org_study_id