Clinical trial NCT01071837: APG101 in Glioblastoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma Multiforme
Keywords: Glioblastoma Multiforme
Lead sponsor: Apogenix AG
Sponsor class: INDUSTRY
First posted: 2010-02-19
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: 6 months rate of progression free survival (PFS6)
timeFrame: 6 month
Secondary outcomes:
measure: Safety and tolerability of APG101
timeFrame: ongoing during study
measure: Progression-free survival
timeFrame: until progression of underlying disease
measure: Objective response rates (OR)
timeFrame: ongoing during study
measure: Duration of response (DR) in responders
timeFrame: ongoing during study
measure: Overall survival
timeFrame: until study and after end of study (by 8-weekly phone calls)
measure: Quality of life
timeFrame: ongoing during study
measure: Cognitive function
timeFrame: ongoing during study
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medizinische Universität Graz, Universitätsklinik für Neurologie Landeskrankenhaus Graz
city: Innsbruck
country: Austria
facility: Universitätsklinik für Neurologie, Landeskrankenhaus Innsbruck
city: Linz
country: Austria
facility: Landesnervenklinik Wagner-Jauregg, Innere Medizin mit Neuroonkologie
city: Wien
country: Austria
facility: Allgemeines Krankenhaus der Stadt Wien, Klinische Onkologie
city: Berlin
country: Germany
facility: Charite Universitätsmedizin Berlin, Klinik für Neurochirugie
city: Bochum
country: Germany
facility: Neurologische Universitätsklinik am Knappschaftskrankenhaus
city: Bonn
country: Germany
facility: Neurologische Universitätsklinik Bonn, Schwerpunkt klinische Neuroonkologie
city: Dresden
country: Germany
facility: Universitätsklinik Dresden, Klinik und Poliklinik für Neurochirurgie
city: Frankfurt/Oder
country: Germany
facility: Klinikum Frankfurt/Oder, Klinik für Strahlentherapie/Radioonkologie
city: Hamburg
country: Germany
facility: Universitätsklinik Hamburg, Klinik für Neurochirugie
city: Heidelberg
country: Germany
facility: Universitätsklinik Heidelberg, Abteilung Neuroonkologie
city: Leipzig
country: Germany
facility: Universität Leipzig, Klinik für Strahlentherapie
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim, Klinik für Neurochirurgie
city: Marburg
country: Germany
facility: Philipps-Universität Marburg, Klinik für Neurologie
city: München
country: Germany
facility: LMU München, Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Campus Großhadern & Campus Innenstadt
city: München
country: Germany
facility: Klinik und Poliklinik für Strahlentherapie/Radiologische Onkologie, Klinikum rechts der Isar, TU München
city: München
country: Germany
facility: Städt. Kliniken München GmbH, Klinikum Bogenhausen, Abt. Neurochirurgie
city: Regensburg
country: Germany
facility: Klinik und Poliklinik der Universität Regensburg, Im Bezirksklinikum
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart, Neurozentrum Neurochirurgie
city: Tuebingen
country: Germany
facility: Universitätsklinikum Tuebingen, Strahlenonkologie
city: Ulm
country: Germany
facility: Uniklinik Ulm, Klinik für Strahlentherapie und Radioonkologie
Study officials:
affiliation: University Hospital Heidelberg, Dept. of Neurooncology, Germany
name: Wolfgang Wick, MD
role: STUDY_DIRECTOR
References: