APG101 in Glioblastoma
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| ClinicalTrials.gov Identifier: NCT01071837 |
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Recruitment Status :
Completed
First Posted : February 19, 2010
Last Update Posted : June 16, 2015
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Glioblastoma Multiforme | Drug: APG101 Procedure: Blood drawing | Phase 2 |
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 (Clinical Trial) |
| Actual Enrollment : | 84 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 Start Date : | December 2009 |
| Actual Primary Completion Date : | October 2014 |
| Actual Study Completion Date : | October 2014 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Re-Irradiation
33% of the patients will be randomized to reirradiation (RT) alone. They will receive 36 Gy (2 Gy per fraction)
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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) |
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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
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Drug: APG101
400mg weekly as intravenous infusion
Other Name: Recombinant fusion protein |
- 6 months rate of progression free survival (PFS6) [ Time Frame: 6 month ]
- Safety and tolerability of APG101 [ Time Frame: ongoing during study ]
- Progression-free survival [ Time Frame: until progression of underlying disease ]
- Objective response rates (OR) [ Time Frame: ongoing during study ]
- Duration of response (DR) in responders [ Time Frame: ongoing during study ]
- Overall survival [ Time Frame: until study and after end of study (by 8-weekly phone calls) ]
- Quality of life [ Time Frame: ongoing during study ]
- Cognitive function [ Time Frame: ongoing during study ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01071837
Show 21 study locations
| Study Director: | Wolfgang Wick, MD | University Hospital Heidelberg, Dept. of Neurooncology, Germany |
| Responsible Party: | Apogenix GmbH |
| ClinicalTrials.gov Identifier: | NCT01071837 |
| Other Study ID Numbers: |
APG101_CD_002 |
| First Posted: | February 19, 2010 Key Record Dates |
| Last Update Posted: | June 16, 2015 |
| Last Verified: | June 2015 |
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Glioblastoma Multiforme |
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Glioblastoma Astrocytoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors |
Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue |