Clinical Trial Results:
Dual blockage with Afatinib and Trastuzumab as neooadjuvant treatment for patients with lo-cally advanced or operable breast cancer receiving taxane-anthracycline containing chemo-therapy (DAFNE study).
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Summary
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EudraCT number |
2011-004704-38 |
Trial protocol |
DE |
Global end of trial date |
19 Feb 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
14 Sep 2022
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First version publication date |
14 Sep 2022
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Other versions |
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Summary report(s) |
CSR Synopsis |
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 |
GBG70
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01594177 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
GBG Forschungs GmbH
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Sponsor organisation address |
Martin-Behaim-Straße 12, Neu-Isenburg, Germany, 63263
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Public contact |
Medicine & Research, GBG Forschungs GmbH, +49 610274800, publications@gbg.de
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Scientific contact |
Medicine & Research, GBG Forschungs GmbH, +49 610274800, publications@gbg.de
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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 |
25 Sep 2014
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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 |
19 Feb 2014
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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 determine the pathological complete response (pCR=ypT0/is ypN0) rates of neoadjuvant treatment of afatinib in combination with weekly paclitaxel + trastuzumab followed by
epirubicin/cyclophosphamide/trastuzumab in patients with HER2-positive primary breast cancer.
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Protection of trial subjects |
The trial protocol including amendments, the patient information and the informed consent were reviewed and approved from a properly constituted IRB/IEC for each site prior to the study start. The trial was in compliance with the International Conference on Harmonization (ICH) - Harmonized Tripartite Guideline for Good Clinical Practice (GCP) (E6), and the Commission Directives in the European Community as well as with the applicable German national laws and regulations, and with Declaration of Helsinki and its revisions in all aspects of preparation, monitoring, reporting, auditing, and archiving.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Feb 2012
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Scientific research | ||
Long term follow-up duration |
10 Years | ||
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 |
Germany: 65
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Worldwide total number of subjects |
65
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EEA total number of subjects |
65
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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) |
53
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From 65 to 84 years |
12
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85 years and over |
0
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Recruitment
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Recruitment details |
Date of the first patient enrolled: May 31st, 2012 Date of the last patient completed: February 19th, 2014 The study was conducted at 11 sites in Germany Overall, 79 patients were screened, 65 started treatment, 47 received the planned treatment and 63 underwent surgery. | ||||||||||||||||||
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Pre-assignment
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Screening details |
Patients with previously untreated, unilateral, nonmetastatic, histologically confirmed invasive breast cancer; tumors either 2 cm or bigger based on clinical or ultrasound assessment or diagnosed as inflammatory breast cancer; centrally confirmed HER2-positive status. | ||||||||||||||||||
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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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afatinib | ||||||||||||||||||
Arm description |
All patients were treated for a total duration of 30 weeks (6 weeks with afatinib and trastuzumab alone, 12 weeks with weekly paclitaxel, afatinib (-1 week) and trastuzumab and 12 weeks with epirubicin/ cyclophosphamide/trastuzumab. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Afatinib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
20 mg oral (daily).
17 weeks (daily; first two weeks: every second day).
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Investigational medicinal product name |
Cyclophosphamide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
600 mg/ m2 i.v.
12 weeks (4 cycles 1 q 22).
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Investigational medicinal product name |
Epirubicin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
90 mg/m2 i.v.
12 weeks (4 cycles 1 q 22).
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Investigational medicinal product name |
Paclitaxel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
80 mg/m2 i.v.
12 weeks (weekly).
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Investigational medicinal product name |
Trastuzumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Loading dose 8 mg/kg body weight i.v., thereafter 6 mg/kg body weight i.v.
30 weeks (10 cycles 1 q 22).
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
HER2-positive breast cancer patients were treated for 6 weeks with afatinib and trastuzumab, followed by 12-week treatment with paclitaxel (80 mg/m2), trastuzumab, and afatinib, followed by 12 weeks with epirubicin , cyclophosphamide, and trastuzumab before surgery. | |||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
afatinib
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Reporting group description |
All patients were treated for a total duration of 30 weeks (6 weeks with afatinib and trastuzumab alone, 12 weeks with weekly paclitaxel, afatinib (-1 week) and trastuzumab and 12 weeks with epirubicin/ cyclophosphamide/trastuzumab. | ||
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End point title |
pCR (ypT0/is ypN0) [1] | ||||||||||
End point description |
Pathological complete response rates: no microscopic evidence of residual viable tumour cells (invasive or noninvasive) in any resected specimens of the breast and axillary nodes (ypT0/is ypN0). Pathological response was assessed considering all removed breast and lymphatic tissues from all surgeries.
The analysis of the primary endpoint of the study was performed using the mITT. A two-sided one group χ2-test was performed to exclude the pCR rate of 55% or lower. Two-sided 90% confidence intervals were calculated according to Pearson and Clopper.
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End point type |
Primary
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End point timeframe |
30 weeks
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The Dafne study was designed as a single arm study, therefore no comparison was available. We expected a pCR rate of 70% and wanted to exclude a pCR rate of 55% or lower with α=0.1 and 1-ß=80%, this required 65 evaluable patients for two-sided one group χ2-test |
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| No statistical analyses for this end point | |||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Overall trial
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
nk
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Reporting groups
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Reporting group title |
afatinib
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Reporting group description |
All patients were treated for a total duration of 30 weeks (6 weeks with afatinib and trastuzumab alone, 12 weeks with weekly paclitaxel, afatinib (-1 week) and trastuzumab and 12 weeks with epirubicin/ cyclophosphamide/trastuzumab. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? Yes | |||
Date |
Amendment |
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02 Oct 2012 |
There was one protocol amendment with the following addition regarding the afatinib intake in chapter 8.1.1.2 Precautions in order to avoid reduced drug absorption and exposure in study patients:
Afatinib should be taken without food (i.e. food should not be consumed for at least three hours before and at least one hour after taking afatinib). |
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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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/25825476 http://www.ncbi.nlm.nih.gov/pubmed/27587600 |
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