Clinical Trial Results:
A randomized, double-blind, placebo-controlled, phase III study to evaluate the efficacy of afatinib (BIBW 2992) in maintenance therapy after postoperative concurrent radiotherapy and chemotherapy for squamous-cell carcinoma of the head and neck : a GORTEC collaborative group study 2010-02
|
Summary
|
|
EudraCT number |
2010-023265-22 |
Trial protocol |
FR |
Global end of trial date |
30 Nov 2020
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
15 Dec 2022
|
First version publication date |
15 Dec 2022
|
Other versions |
|
Summary report(s) |
RRF |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
ET2010-005
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01427478 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Centre Léon Bérard
|
||
Sponsor organisation address |
28 rue Laennec, Lyon, France, 69008
|
||
Public contact |
DRCI
Séverine METZGER, Centre Léon Bérard, 00 334 78 78 28 28,
|
||
Scientific contact |
Centre Léon Bérard
Dr Séverine RACADOT
Dr Pascal POMMIER, Centre Léon Bérard, 00 334 78 78 28 28,
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
22 Nov 2021
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
30 Nov 2020
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
Démontrer la supériorité d’un traitement de maintenance de 12 mois par afatinib par rapport à un placebo, après une radiothérapie et chimiothérapie concomitante par cisplatine, sur l’amélioration du taux de survie sans maladie (DFS) à 2 ans
|
||
Protection of trial subjects |
The investigator will have to proceed to the following information/procedures during the screening visit:
- Fully inform the patient of the study treatments, the objectives and the design of the study, answer to any questions that the patient may have and ensure that the patient understands the potential risks and benefits of participating in the study before signing the informed consent form. None study-related procedure can be started before ICF is signed and dated by both the patient (and impartial witness, if applicable) and the investigator
- Check the eligibility criteria list and perform the exams
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 Sep 2011
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
France: 134
|
||
Worldwide total number of subjects |
134
|
||
EEA total number of subjects |
134
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
107
|
||
From 65 to 84 years |
27
|
||
85 years and over |
0
|
||
|
||||||||||
|
Recruitment
|
||||||||||
Recruitment details |
Patients were recruited at the time of enrolment at the participating sites. The declared investigator, after having identified a potential candidate for the study, informed her orally of the terms of the study and provide her with : an information note, An informed consent form that has been dated and signed by the patient and the investigator. | |||||||||
|
Pre-assignment
|
||||||||||
Screening details |
None study-related procedure can be started before ICF was signed and dated by both the patient (and impartial witness, if applicable) and the investigator - Checked the eligibility criteria list and perform the exams. | |||||||||
|
Period 1
|
||||||||||
Period 1 title |
Overall trial (overall period)
|
|||||||||
Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
|
|||||||||
Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator | |||||||||
|
Arms
|
||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||
|
Arm title
|
BIBW | |||||||||
Arm description |
- | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Afatinib
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||
Routes of administration |
Oral use
|
|||||||||
Dosage and administration details |
Maintenance treatment with afatinib (GIOTRIF®) for 1 year: at a dose of 40 mg/day for one month, then 50 mg/day for the following 11 months.
|
|||||||||
|
Arm title
|
Placebo | |||||||||
Arm description |
- | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Afatinib placebo
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||
Routes of administration |
Oral use
|
|||||||||
Dosage and administration details |
Afatinib placebo maintenance for 1 year: 40 mg/day for one month, then 50 mg/day for the next 11 months.
|
|||||||||
|
||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Overall trial
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Subject analysis sets
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Analysis population
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The intention-to-treat (ITT) population includes all randomised patients.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
BIBW
|
||
Reporting group description |
- | ||
Reporting group title |
Placebo
|
||
Reporting group description |
- | ||
Subject analysis set title |
Analysis population
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The intention-to-treat (ITT) population includes all randomised patients.
|
||
|
|||||||||||||
End point title |
Disease free survival | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
2 years
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Overall survival | ||||||||||||
Comparison groups |
BIBW v Placebo
|
||||||||||||
Number of subjects included in analysis |
134
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
= 0.9553 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Log hazard ratio | ||||||||||||
Point estimate |
0.99
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.59 | ||||||||||||
upper limit |
1.65 | ||||||||||||
|
|||||||||||
|
Adverse events information [1]
|
|||||||||||
Timeframe for reporting adverse events |
The investigator collects (spontaneous patient report or questionning) and immediately notifies the sponsor of all SAEs, in a written report, wether or not theay are deemed to be attributable to research and wich occur during the study.
|
||||||||||
Assessment type |
Systematic | ||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||
Dictionary name |
MedDRA | ||||||||||
Dictionary version |
21.0
|
||||||||||
|
Reporting groups
|
|||||||||||
Reporting group title |
Overall
|
||||||||||
Reporting group description |
- | ||||||||||
|
|||||||||||
| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||
|
|||||||||||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Non-serious events were collected and not specifically reported. |
|||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
15 May 2012 |
- Updated the newsletter following the change in the BI.
- Increased the time to start radiation therapy from 6 to 8 weeks after surgery.
- Added criteria for non-randomization.
- Updated the list of participating centers |
||
24 Sep 2012 |
- Transmit the new Afatinib Investigator Brochure.
- Make changes regarding prohibited treatments during maintenance therapy.
- Adapt patient information letter.
- Update the list of investigators. |
||
03 Feb 2014 |
- Modification of the study design (simultaneous inclusion and randomization). Adjuvant radiochemotherapy with cisplatin (is removed from the study procedures and the inclusion and non-inclusion criteria as well as the treatment, procedures and follow-up before randomization are modified accordingly.
- Modification of the post-maintenance follow-up by decreasing the frequency of visits (cardiac follow-up frequency unchanged): at M1, M3 and M12 (instead of every 2 months) and then every year (instead of every 3 months) until the end of the 5th year.
- BI update impacting patient safety and determination of expected or unexpected nature of a suspected SAE (impact on anticipated protocol with liver follow-up): modification of the section regarding potential risks in the information note.
- Modification of the contact person with the sponsor: Séverine METZGER replaces Sophie DUSSART as project manager.
- Update of the investigators list. |
||
30 Jun 2014 |
- Modification of the IMPD submitted at the time of the initial application by the Boehringer laboratory, owner of the data relating to IMP (afatinib), which obtained a marketing authorization (centralized procedure) on 2013/09/25 under the name of GIOTRIF in another indication (treatment of adult patients naïve to anti EGFR TKIs with locally advanced or metastatic non-small cell bronchial cancer NSCLC) that presents an activating mutation(s) of EGFR).
The supply of the IMP will be done accordingly either with the tablets already used in this trial or with those that conform to the product that has obtained the standard IMP : only the color may vary, the packaging and labeling remain identical.
- Update of the investigator list. |
||
03 Sep 2020 |
- Update of the list of investigators. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
