Clinical Trial Results:
Continous treatment with bevacizumab in elderly patients with mCRC: an open label, single arm, prospective phase IV trial to evaluate outcome and safety of continuous bevacizumab treatment in combination with chemotherapy over disease progression
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Summary
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EudraCT number |
2014-003844-11 |
Trial protocol |
SE |
Global end of trial date |
11 Dec 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Dec 2019
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First version publication date |
27 Dec 2019
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Other versions |
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Summary report(s) |
GRACE Clinical Study Report |
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 |
ML29242
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Department of Oncology, Linköping University of Hospital
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Sponsor organisation address |
Linköping University of Hospital, Linköping, Sweden, 58185
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Public contact |
Gunnar Adell, Dept of Onc, Linköping Uni Hospital, Department of Oncology, Linköping University Hospital, +46 101030000, gunnar.adell@regionostergotland.se
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Scientific contact |
Gunnar Adell, Dept of Onc, Linköping Uni Hospital, Department of Oncology, Linköping University Hospital, +46 1010300000, gunnar.adell@regionostergotland.se
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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 |
06 Dec 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
11 Dec 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
11 Dec 2018
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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 evaluate the feasibility of continous treatment with bevacizumab beyond disease progression in an elderly community based patient population by assessment of overall survival.
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Protection of trial subjects |
Written informed consent was obtained from each patient participating in the study before any study specific screening procedure was performed. Informed consent was signed after adequate explanation of the aims, methods, anticipated benefits and potential hazards of the study.
The investigator must assure that subjects’ anonymity will be maintained and that their identities are protected from unauthorized parties. On eCRFs or other documents subjects should not be identified by their names but by an identification code. The investigator should keep a subject enrolment log showing codes, names and addresses in strict confidence.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
02 Nov 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Sweden: 48
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Worldwide total number of subjects |
48
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EEA total number of subjects |
48
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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) |
0
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From 65 to 84 years |
46
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85 years and over |
2
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Recruitment
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Recruitment details |
Recrutiment: 02nov2015 to 11dec2018 | ||||||||||||||
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Pre-assignment
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Screening details |
• Demographics and medical history – includes age, gender and current diseases • Information on cancer and treatment history • Concurrent disease – diseases potentially • Physical examination and vital signs – include height, weight, pulse, blood pressure • ECG | ||||||||||||||
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Pre-assignment period milestones
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Number of subjects started |
48 | ||||||||||||||
Number of subjects completed |
48 | ||||||||||||||
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Period 1
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Period 1 title |
overall trial (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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Arm title
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bevacizumab | ||||||||||||||
Arm description |
open label, singel arm | ||||||||||||||
Arm type |
single | ||||||||||||||
Investigational medicinal product name |
Bevacizumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Bevacizumab was administered at a fixed dose equivalent to 2.5 mg/kg per week; either as 7.5 mg /kg every three weeks (q3w) or 5 mg/kg every two weeks (2qw). Bevacizumab is a concentrate that should be diluted with sodium chloride (NaCl) for intravenous infusions
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
overall survival
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Overall survival was measured as the time from the date of enrolment to the date of death. Patients without death date were censored at the date when the trial was terminated (11dec2018).
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End points reporting groups
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Reporting group title |
bevacizumab
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Reporting group description |
open label, singel arm | ||
Subject analysis set title |
overall survival
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Overall survival was measured as the time from the date of enrolment to the date of death. Patients without death date were censored at the date when the trial was terminated (11dec2018).
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End point title |
To assess overall Sutvival (OS) from time of inclusion | ||||||||||||
End point description |
To assess Overall survival (OS) from time of inclusion
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End point type |
Primary
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End point timeframe |
Overall survival (OS) from time of inclusion
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Statistical analysis title |
kaplan-meier | ||||||||||||
Statistical analysis description |
The main efficacy endpoint overall survival was estimated using the Kaplan-Meier method.
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Comparison groups |
bevacizumab v overall survival
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Number of subjects included in analysis |
78
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | ||||||||||||
P-value |
= 0 [2] | ||||||||||||
Method |
no comparison | ||||||||||||
Parameter type |
Median difference (final values) | ||||||||||||
Point estimate |
17.4
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Confidence interval |
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95% | ||||||||||||
sides |
2-sided
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lower limit |
12.6 | ||||||||||||
upper limit |
22.3 | ||||||||||||
| Notes [1] - only description, no comparison [2] - no comparison were made |
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Adverse events information
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Timeframe for reporting adverse events |
From baseline to 30 Days after last dose of study treatment should be recorded
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Adverse event reporting additional description |
Adverse events ≥ grade 3 and any grade ATEs experienced up until 30 days after the last dose of study treatment should be recorded in the eCRF and followed up until they have returned to baseline status or stabilized. All AEs ≥ grade 3 including any grade ATE considered related to bevacizumab which occur up to 6 months after the last dose should al
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
NCI CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4
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Reporting groups
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Reporting group title |
Bevacizumab
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Reporting group description |
open label, singel arm | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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. | |||
| 100 patients were planned to be enrolled, allowing a drop-out rate of 10%. Estimated accrual time of 36 months. The study was early terminated at 37 months after study initiation and after 48 patients had been included, of which 19% dropped- out. The | |||
