Back to results

APG101 in Glioblastoma

Primary Purpose

Glioblastoma Multiforme

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

APG101

Blood drawing

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring Glioblastoma Multiforme

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Medizinische Universität Graz, Universitätsklinik für Neurologie Landeskrankenhaus Graz
Universitätsklinik für Neurologie, Landeskrankenhaus Innsbruck
Landesnervenklinik Wagner-Jauregg, Innere Medizin mit Neuroonkologie
Allgemeines Krankenhaus der Stadt Wien, Klinische Onkologie
Charite Universitätsmedizin Berlin, Klinik für Neurochirugie
Neurologische Universitätsklinik am Knappschaftskrankenhaus
Neurologische Universitätsklinik Bonn, Schwerpunkt klinische Neuroonkologie
Universitätsklinik Dresden, Klinik und Poliklinik für Neurochirurgie
Klinikum Frankfurt/Oder, Klinik für Strahlentherapie/Radioonkologie
Universitätsklinik Hamburg, Klinik für Neurochirugie
Universitätsklinik Heidelberg, Abteilung Neuroonkologie
Universität Leipzig, Klinik für Strahlentherapie
Universitätsmedizin Mannheim, Klinik für Neurochirurgie
Philipps-Universität Marburg, Klinik für Neurologie
LMU München, Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Campus Großhadern & Campus Innenstadt
Klinik und Poliklinik für Strahlentherapie/Radiologische Onkologie, Klinikum rechts der Isar, TU München
Städt. Kliniken München GmbH, Klinikum Bogenhausen, Abt. Neurochirurgie
Klinik und Poliklinik der Universität Regensburg, Im Bezirksklinikum
Klinikum Stuttgart, Neurozentrum Neurochirurgie
Universitätsklinikum Tuebingen, Strahlenonkologie
Uniklinik Ulm, Klinik für Strahlentherapie und Radioonkologie

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Re-Irradiation

Re-Irradiation + APG101

Arm Description

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

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

Outcomes

Primary Outcome Measures

6 months rate of progression free survival (PFS6)

Secondary Outcome Measures

Safety and tolerability of APG101

Progression-free survival

Objective response rates (OR)

Duration of response (DR) in responders

Overall survival

Quality of life

Cognitive function

Full Information

NCT ID

NCT01071837

First Posted

February 18, 2010

Last Updated

June 15, 2015

Sponsor

Apogenix GmbH

1. Study Identification

Unique Protocol Identification Number

NCT01071837

Brief Title

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

2. Study Status

Record Verification Date

June 2015

Overall Recruitment Status

Completed

Study Start Date

December 2009 (undefined)

Primary Completion Date

October 2014 (Actual)

Study Completion Date

October 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Apogenix GmbH

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma Multiforme

Keywords

Glioblastoma Multiforme

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

84 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Re-Irradiation

Arm Type

Active Comparator

Arm Description

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

Arm Title

Re-Irradiation + APG101

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

APG101

Other Intervention Name(s)

Recombinant fusion protein

Intervention Description

400mg weekly as intravenous infusion

Intervention Type

Procedure

Intervention Name(s)

Blood drawing

Intervention Description

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

Primary Outcome Measure Information:

Title

6 months rate of progression free survival (PFS6)

Time Frame

6 month

Secondary Outcome Measure Information:

Title

Safety and tolerability of APG101

Time Frame

ongoing during study

Title

Progression-free survival

Time Frame

until progression of underlying disease

Title

Objective response rates (OR)

Time Frame

ongoing during study

Title

Duration of response (DR) in responders

Time Frame

ongoing during study

Title

Overall survival

Time Frame

until study and after end of study (by 8-weekly phone calls)

Title

Quality of life

Time Frame

ongoing during study

Title

Cognitive function

Time Frame

ongoing during study

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Wolfgang Wick, MD

Organizational Affiliation

University Hospital Heidelberg, Dept. of Neurooncology, Germany

Official's Role

Study Director

Facility Information:

Facility Name

Medizinische Universität Graz, Universitätsklinik für Neurologie Landeskrankenhaus Graz

City

Graz

ZIP/Postal Code

8036

Country

Austria

Facility Name

Universitätsklinik für Neurologie, Landeskrankenhaus Innsbruck

City

Innsbruck

ZIP/Postal Code

6020

Country

Austria

Facility Name

Landesnervenklinik Wagner-Jauregg, Innere Medizin mit Neuroonkologie

City

Linz

ZIP/Postal Code

4020

Country

Austria

Facility Name

Allgemeines Krankenhaus der Stadt Wien, Klinische Onkologie

City

Wien

ZIP/Postal Code

1090

Country

Austria

Facility Name

Charite Universitätsmedizin Berlin, Klinik für Neurochirugie

City

Berlin

ZIP/Postal Code

13353

Country

Germany

Facility Name

Neurologische Universitätsklinik am Knappschaftskrankenhaus

City

Bochum

ZIP/Postal Code

44892

Country

Germany

Facility Name

Neurologische Universitätsklinik Bonn, Schwerpunkt klinische Neuroonkologie

City

Bonn

ZIP/Postal Code

53105

Country

Germany

Facility Name

Universitätsklinik Dresden, Klinik und Poliklinik für Neurochirurgie

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

Klinikum Frankfurt/Oder, Klinik für Strahlentherapie/Radioonkologie

City

Frankfurt/Oder

ZIP/Postal Code

15236

Country

Germany

Facility Name

Universitätsklinik Hamburg, Klinik für Neurochirugie

City

Hamburg

ZIP/Postal Code

20246

Country

Germany

Facility Name

Universitätsklinik Heidelberg, Abteilung Neuroonkologie

City

Heidelberg

ZIP/Postal Code

69120

Country

Germany

Facility Name

Universität Leipzig, Klinik für Strahlentherapie

City

Leipzig

ZIP/Postal Code

04103

Country

Germany

Facility Name

Universitätsmedizin Mannheim, Klinik für Neurochirurgie

City

Mannheim

ZIP/Postal Code

68167

Country

Germany

Facility Name

Philipps-Universität Marburg, Klinik für Neurologie

City

Marburg

ZIP/Postal Code

35039

Country

Germany

Facility Name

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

City

München

ZIP/Postal Code

81377

Country

Germany

Facility Name

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

City

München

ZIP/Postal Code

81675

Country

Germany

Facility Name

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

City

München

ZIP/Postal Code

81925

Country

Germany

Facility Name

Klinik und Poliklinik der Universität Regensburg, Im Bezirksklinikum

City

Regensburg

ZIP/Postal Code

93053

Country

Germany

Facility Name

Klinikum Stuttgart, Neurozentrum Neurochirurgie

City

Stuttgart

ZIP/Postal Code

70174

Country

Germany

Facility Name

Universitätsklinikum Tuebingen, Strahlenonkologie

City

Tuebingen

ZIP/Postal Code

72076

Country

Germany

Facility Name

Uniklinik Ulm, Klinik für Strahlentherapie und Radioonkologie

City

Ulm

ZIP/Postal Code

89081

Country

Germany

12. IPD Sharing Statement

Learn more about this trial

APG101 in Glioblastoma

We'll reach out to this number within 24 hrs