Clinical Trial Results:
A Randomised phase II study with the combination of Xeloda (Capecitabine) plus Navelbine Oral ( Vinorelbine) day 1 and day 8 every 3. week versus Xeloda plus Navelbine Oral given metronimic as 1. or 2. line chemotherapy to patients with HER2 negative local metastatic breastcancer.

Trial information Top of page
Trial identification
Sponsor protocol code	Aarhus University Hospital
Additional study identifiers
ISRCTN number	-
US NCT number	NCT01941771
WHO universal trial number (UTN)	-
Other trial identifiers	Aarhus University Hospital: Department of oncology
Sponsors
Sponsor organisation name	Aarhus University Hospital
Sponsor organisation address	Palle Juul Jensens Boulevard 99, Aarhus, Denmark, 8200
Public contact	Clinical Trial Unit , Aarhus University Hospital, 0045 89494440, svelan@rm.dk
Scientific contact	Clinical Trial Unit , Aarhus University Hospital, 0045 89494440, svelan@rm.dk
Sponsor organisation name	Aarhus University Hospital
Sponsor organisation address	Palle Juul Jensens Boulevard 99, Aarhus, Denmark,
Public contact	cllinical research unit, Department of oncology, 45 24839896, annebrem@rm.dk
Scientific contact	cllinical research unit, Department of oncology, 45 24839896, annebrem@rm.dk
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	01 Oct 2020
Is this the analysis of the primary completion data?	No
Global end of trial reached?	Yes
Global end of trial date	11 Dec 2019
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	To compare the effect of an experimental chemotherapy arm, where Navelbine is given together with Xeloda in a metronomic manner to a standard treatment arm of Navelbine and Xeloda. We expected that the experimental arm was better than the standard treatment arm
Protection of trial subjects	Data was anonymized. No other protection of trial subjects
Background therapy	Standart supportive care for nausea and diahrrea if nessesary. Standard treatment of pain and infections if any
Evidence for comparator	-
Actual start date of recruitment	02 Jan 2012
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	Denmark: 120
Worldwide total number of subjects	120
EEA total number of subjects	120
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)	100
From 65 to 84 years	20
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	Patients were recruited at the Department of Oncology, University Hospital of Aarhus
Pre-assignment
Screening details	Patients treated for metastatic breast cancer in our department.
Pre-assignment period milestones
Number of subjects started	120
Number of subjects completed	120
Period 1
Period 1 title	inclusion in the trial (overall period)
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Not blinded
Blinding implementation details	open randomised trial
Arms
Are arms mutually exclusive	Yes
Arm title	arm a
Arm description	standard chemotreapy with xeloda day 1-14 and navalbine day 1-8
Arm type	Active comparator
Investigational medicinal product name	Navelbine
Investigational medicinal product code	L01CA
Other name
Pharmaceutical forms	Capsule, soft + tablet
Routes of administration	Oral use
Dosage and administration details	please see the article
Investigational medicinal product name	Navelbine
Investigational medicinal product code	L01CA
Other name
Pharmaceutical forms	Capsule, soft + tablet
Routes of administration	Oral use
Dosage and administration details	please see the article
Arm title	arm b
Arm description	metronomic vinorlebine and standard xeloda day 1-14
Arm type	Experimental
Investigational medicinal product name	Navelbine
Investigational medicinal product code	L01CA
Other name
Pharmaceutical forms	Capsule, soft + tablet
Routes of administration	Oral use
Dosage and administration details	please see the article
Number of subjects in period 1 arm a arm b Started 62 58 Completed 60 58 Not completed 2 0      Consent withdrawn by subject 1 -      Protocol deviation 1 -

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	inclusion in the trial
Reporting group description	-
Reporting group values inclusion in the trial Total Number of subjects 120 120 Age categorical age Units: Subjects     In utero 0 0     Preterm newborn infants (gestational age < 37 wks) 0 0     Newborns (0-27 days) 0 0     Infants and toddlers (28 days-23 months) 0 0     Children (2-11 years) 0 0     Adolescents (12-17 years) 0 0     Adults (18-64 years) 100 100     From 65-84 years 20 20     85 years and over 0 0 Gender categorical sex Units: Subjects     Female 120 120     Male 0 0
Subject analysis sets
Subject analysis set title	arm a and arm b
Subject analysis set type	Intention-to-treat
Subject analysis set description	Randomized trial Arm conventional chemotrerpy, trial arm B metronomic chemoterapy
Subject analysis sets values arm a and arm b Number of subjects 118 Age categorical age Units: Subjects     In utero 0     Preterm newborn infants (gestational age < 37 wks) 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) 98     From 65-84 years 20     85 years and over 0 Age continuous Units:      ( ) Gender categorical sex Units: Subjects     Female 118     Male 0

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	arm a
Reporting group description	standard chemotreapy with xeloda day 1-14 and navalbine day 1-8
Reporting group title	arm b
Reporting group description	metronomic vinorlebine and standard xeloda day 1-14
Subject analysis set title	arm a and arm b
Subject analysis set type	Intention-to-treat
Subject analysis set description	Randomized trial Arm conventional chemotrerpy, trial arm B metronomic chemoterapy

End points Top of page

Primary: response rate Top of page
End point title	response rate
End point description	Recist 1.0
End point type	Primary
End point timeframe	2012-2019
End point values arm a arm b Number of subjects analysed 60 58 Units: patients benefits of treatments 60 58
Statistical analysis title	calculation of response rates
Comparison groups	arm a v arm b
Number of subjects included in analysis	118
Analysis specification	Pre-specified
Analysis type	superiority
P-value	≥ 0.05
Method	Logrank
Parameter type	Odds ratio (OR)
Confidence interval
level	95%
sides	2-sided
lower limit	-
upper limit	-
Variability estimate	Standard deviation

Primary: response rate Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	2012-2019
Adverse event reporting additional description	See attached article
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	CTCAE
Dictionary version	4
Reporting groups
Reporting group title	adverse events
Reporting group description	Please see the table in the article for details
Serious adverse events adverse events Total subjects affected by serious adverse events      subjects affected / exposed 33 / 118 (27.97%)      number of deaths (all causes) 80      number of deaths resulting from adverse events 2 General disorders and administration site conditions stated in the article Additional description: Please see the article      subjects affected / exposed 33 / 118 (27.97%)      occurrences causally related to treatment / all 33 / 33      deaths causally related to treatment / all 2 / 2
Frequency threshold for reporting non-serious adverse events: 1%
Non-serious adverse events adverse events Total subjects affected by non serious adverse events      subjects affected / exposed 80 / 118 (67.80%) Blood and lymphatic system disorders Stated in the article Additional description: Stated in the article      subjects affected / exposed 80 / 118 (67.80%)      occurrences all number 80

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? No
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.
Phase 2 study. Not powered to compare survival the two arms.
Online references
http://www.ncbi.nlm.nih.gov/pubmed/33259244

More information Top of page