Clinical Trial Results:
Phase II clinicPhase II clinical trial on the combination of avelumab and axitinib for the treatment of patients with recurrent glioblastomaal trial on the combination of avelumab and axitinib for the treatment of patients with recurrent glioblastoma
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Summary
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EudraCT number |
2017-000200-23 |
Trial protocol |
BE |
Global end of trial date |
16 Sep 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
12 May 2021
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First version publication date |
12 May 2021
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Other versions |
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Summary report(s) |
Gliavax article |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
2017-BN-001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03291314 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
UZ Brussel
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Sponsor organisation address |
Laarbeeklaan 101, Jette, Belgium, 1090
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Public contact |
Bart Neyns, UZ Brussel, 0032 24775447, bart.neyns@uzbrussel.be
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Scientific contact |
Bart Neyns, UZ Brussel, 0032 24775447, bart.neyns@uzbrussel.be
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
16 Sep 2020
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
16 Sep 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To estimate the anti-tumor effect of combination therapy with Avelumab and Axitinib in patients with recurrent/progressive glioblastoma following prior therapy with surgery, radiation therapy and Temozolomide (on both strata seperatly)
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Protection of trial subjects |
Signed Informed consent, in this consent is explained that the patient data is anonymized.
Safety data will be collected on a continuous basis and will be reviewed by the Sponsor in order to ensure that it is appropriate to continue the study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Mar 2017
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy, Safety | ||
Long term follow-up duration |
6 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 54
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Worldwide total number of subjects |
54
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EEA total number of subjects |
54
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
47
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From 65 to 84 years |
7
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were screened for eligibility by history, physical examination, blood and urinary analysis (including blood chemistry, hematological, endocrinological tests and dipstick proteinuria), electrocardiography, MRI of the brain and 18F-FET-PET/CT of the brain | |||||||||
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Pre-assignment
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Screening details |
Willing and able to give written informed consent Histologically confirmed diagnosis of World Health Organization Grade IV malignant glioma Documentation of recurrent | |||||||||
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Period 1
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Period 1 title |
Treatment (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Cohort 1 | |||||||||
Arm description |
Axitinib and Avelumab | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Axitinib
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Investigational medicinal product code |
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Other name |
Inlyta
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Axitinib 5mg twice a day
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Investigational medicinal product name |
Avelumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for solution for infusion
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Routes of administration |
Intravenous drip use
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Dosage and administration details |
Avelumab 10mg/kg until confirmed progression of disease, unacceptable toxicity, the patient's refusal to continue study treatment, or death of the patient.
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Arm title
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Cohort 2 | |||||||||
Arm description |
Axitinib | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Axitinib
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Investigational medicinal product code |
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Other name |
Inlyta
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Axitinib 5mg twice a day
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Baseline characteristics reporting groups
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Reporting group title |
Treatment (overall period)
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Cohort 1
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Reporting group description |
Axitinib and Avelumab | ||
Reporting group title |
Cohort 2
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Reporting group description |
Axitinib | ||
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End point title |
Progression free survival (6-month PFS%) | |||||||||
End point description |
The percentage of patients who are alive and free-from confirmed tumor progression at 6-month (24 weeks) following the date of randomisation (6-month PFS%)
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End point type |
Primary
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End point timeframe |
Progression-free survival at 6 months (6-m-PFS%), per immunotherapy response assessment for neuro-oncology criteria
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Statistical analysis title |
one-stage Fleming design | |||||||||
Statistical analysis description |
Sample size Cohort-1 is determined according to one-stage Fleming design. Avelumab plus axitinib worthy of further investigations if a 6-m-PFS% of >50% is observed (p(0)=0.30 and p(1)= 0.50). With alpha error of 0.10, and a beta error of 0.20, a sample size of 26 patients is required.The outcome of patients recruited to Cohort-2 is considered to be of an exploratory nature and no predefined statistical hypothesis was used to calculate the sample size for this cohort.
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Comparison groups |
Cohort 1 v Cohort 2
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Number of subjects included in analysis |
54
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | |||||||||
P-value |
< 0.05 [2] | |||||||||
Method |
see remark above | |||||||||
Confidence interval |
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| Notes [1] - determination of efficacy in a Phase two trial design [2] - not relevant for this study, as both cohorts were not compared to each other |
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Adverse events information
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Timeframe for reporting adverse events |
Throughout the duration of the study
Clinical and blood parameters were assessed every 3 weeks. Adverse events (AEs) were graded for
severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events
(version 4.0).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4
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Reporting groups
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Reporting group title |
Study population
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
