Clinical Trial Results:
Intra-hepatic chemotherapy with oxaliplatin every second week in combination with systemic capecitabine and in patients with a HER2-positive tumour in combination with trastuzumab (Herceptin®) in patient with non-resectable liver metastases from breast cancer. A phase II trial in patients with limited extrahepatic disease.

Trial information Top of page
Trial identification
Sponsor protocol code	MA0918
Additional study identifiers
ISRCTN number	-
US NCT number	NCT01387295
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Herlev Hospital
Sponsor organisation address	Herlev Ringvej 75, Herlev, Denmark, 2730
Public contact	Dorte Nielsen, Department of Oncology Herlev Hospital, +45 38682344, dorte.nielsen.01@regionh.dk
Scientific contact	Dorte Nielsen, Department of Oncology Herlev Hospital, +45 38682344, dorte.nielsen.01@regionh.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 Sep 2017
Is this the analysis of the primary completion data?	Yes
Primary completion date	01 May 2017
Global end of trial reached?	Yes
Global end of trial date	01 May 2017
Was the trial ended prematurely?	Yes
General information about the trial
Main objective of the trial	Response rate Number of patients with complete or partial response in the liver (RECIST version 1.1)
Protection of trial subjects	Eligibility criteria, Dose modification no additional measures
Background therapy	NA
Evidence for comparator	NA
Actual start date of recruitment	01 Oct 2009
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Denmark: 38
Worldwide total number of subjects	38
EEA total number of subjects	38
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)	30
From 65 to 84 years	8
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	Patients recruited at single site at Herlev Hospital, Department of Oncology, Denmark, Recruitment was open from October 2009 to September 2016
Pre-assignment
Screening details	Patients with histologically confirmed adenocarcinoma of the breast with main metastases in liver and limited extrahepatic disease were allowed. Liver metastases evaluated not suitable for local ablation by RFA, SBRT, or surgery and had <70% of the liver affected. Extra-hepatic metastasis without progression within past 6 months.
Period 1
Period 1 title	Overall trial (overall period)
Is this the baseline period?	Yes
Allocation method	Not applicable
Blinding used	Not blinded
Arms
Arm title	Protocol treatment
Arm description	Single Arm study
Arm type	Experimental
Investigational medicinal product name	Oxaliplatin
Investigational medicinal product code
Other name
Pharmaceutical forms	Concentrate for solution for infusion
Routes of administration	Intrahepatic use , Intravenous use
Dosage and administration details	Patients received oxaliplatin every two weeks alternating between hepatic arterial and systemic administration. Dose was at 85 mg/m2.
Investigational medicinal product name	Capecitabine
Investigational medicinal product code
Other name
Pharmaceutical forms	Film-coated tablet
Routes of administration	Oral use
Dosage and administration details	Capecitabine was given at a daily dose of 1300 mg/m2 on a continuous schedule
Investigational medicinal product name	Trastuzumab
Investigational medicinal product code
Other name
Pharmaceutical forms	Concentrate for solution for infusion
Routes of administration	Intravenous use
Dosage and administration details	Patients with HER-2 positive tumors received additional trastuzumab 8 mg/kg on day 1 followed by 6 mg/kg every third week.
Number of subjects in period 1 Protocol treatment Started 38 Completed 38

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Overall trial
Reporting group description	-
Reporting group values Overall trial Total Number of subjects 38 38 Age categorical 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) 0     From 65-84 years 0     85 years and over 0 Age continuous Units: years     median (full range (min-max)) 54.5 (31 to 72) - Gender categorical Units: Subjects     Female 38 38     Male 0 0

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Protocol treatment
Reporting group description	Single Arm study

End points Top of page

Primary: Response rate (hepatic) Top of page
End point title	Response rate (hepatic) [1]
End point description
End point type	Primary
End point timeframe	treatment start to progression of disease or death
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: single arm trial
End point values Protocol treatment Number of subjects analysed 38 Units: number of patients     CR 2     PR 13     SD 21     PD 1     Not evaluable 1
No statistical analyses for this end point

Primary: Response rate (hepatic) Top of page

Secondary: Overall reponse rate Top of page
End point title	Overall reponse rate
End point description
End point type	Secondary
End point timeframe	treatment start to progression of disease or death
End point values Protocol treatment Number of subjects analysed 38 Units: number of patients     CR 0     PR 15     SD 21     PD 2
No statistical analyses for this end point

Secondary: Overall reponse rate Top of page

Secondary: PFS Top of page
End point title	PFS
End point description
End point type	Secondary
End point timeframe	PFS was calculated as the period from the first treatment to disease progression or death of any cause.
End point values Protocol treatment Number of subjects analysed 38 Units: months     median (full range (min-max)) 12.8 (6.9 to 18.6)
No statistical analyses for this end point

Secondary: PFS Top of page

Secondary: OS Top of page
End point title	OS
End point description
End point type	Secondary
End point timeframe	OS was calculated as the time from the first treatment to death from any cause or until May 1st 2017
End point values Protocol treatment Number of subjects analysed 38 Units: months     median (full range (min-max)) 24.0 (17.2 to 30.8)
No statistical analyses for this end point

Secondary: OS Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	Informed consent to 30 days after last treatment
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	NCI-CTCAE
Dictionary version	3.0
Reporting groups
Reporting group title	Protocol treatment
Reporting group description	Single Arm study
Serious adverse events Protocol treatment Total subjects affected by serious adverse events      subjects affected / exposed 8 / 38 (21.05%)      number of deaths (all causes) 33      number of deaths resulting from adverse events 0 Injury, poisoning and procedural complications Morphine toxication      subjects affected / exposed 1 / 38 (2.63%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Vascular disorders Pulmonary embolism      subjects affected / exposed 2 / 38 (5.26%)      occurrences causally related to treatment / all 0 / 2      deaths causally related to treatment / all 0 / 0 General disorders and administration site conditions Fever      subjects affected / exposed 1 / 38 (2.63%)      occurrences causally related to treatment / all 1 / 1      deaths causally related to treatment / all 0 / 0 Hepatobiliary disorders gallbladder stone      subjects affected / exposed 1 / 38 (2.63%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Infections and infestations Infection      subjects affected / exposed 3 / 38 (7.89%)      occurrences causally related to treatment / all 0 / 3      deaths causally related to treatment / all 0 / 0 Metabolism and nutrition disorders Diabetes mellitus      subjects affected / exposed 1 / 38 (2.63%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0
Frequency threshold for reporting non-serious adverse events: 5%
Non-serious adverse events Protocol treatment Total subjects affected by non serious adverse events      subjects affected / exposed 38 / 38 (100.00%) Investigations Alanine aminotransferase increased      subjects affected / exposed 15 / 38 (39.47%)      occurrences all number 54 Aspartate aminotransferase increased      subjects affected / exposed 19 / 38 (50.00%)      occurrences all number 77 Alkaline phosphatase increased      subjects affected / exposed 17 / 38 (44.74%)      occurrences all number 46 Amylase increased      subjects affected / exposed 14 / 38 (36.84%)      occurrences all number 35 Hyperbilirubinaemia      subjects affected / exposed 3 / 38 (7.89%)      occurrences all number 8 Thrombocytopenia      subjects affected / exposed 17 / 38 (44.74%)      occurrences all number 82 Neutropenia      subjects affected / exposed 15 / 38 (39.47%)      occurrences all number 25 Nervous system disorders Dysaesthesia      subjects affected / exposed 35 / 38 (92.11%)      occurrences all number 304 Peripheral motor neuropathy      subjects affected / exposed 11 / 38 (28.95%)      occurrences all number 41 Peripheral sensory neuropathy      subjects affected / exposed 29 / 38 (76.32%)      occurrences all number 179 General disorders and administration site conditions Allergic reaction      subjects affected / exposed 3 / 38 (7.89%)      occurrences all number 6 Fatigue      subjects affected / exposed 30 / 38 (78.95%)      occurrences all number 159 Fever      subjects affected / exposed 9 / 38 (23.68%)      occurrences all number 12 pain      subjects affected / exposed 23 / 38 (60.53%)      occurrences all number 59 Blood and lymphatic system disorders Anaemia      subjects affected / exposed 9 / 38 (23.68%)      occurrences all number 12 Gastrointestinal disorders Diarrhoea      subjects affected / exposed 21 / 38 (55.26%)      occurrences all number 55 Stomatitis      subjects affected / exposed 21 / 38 (55.26%)      occurrences all number 62 Nausea      subjects affected / exposed 34 / 38 (89.47%)      occurrences all number 119 Vomiting      subjects affected / exposed 20 / 38 (52.63%)      occurrences all number 36 Dyspepsia      subjects affected / exposed 5 / 38 (13.16%)      occurrences all number 12 Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome      subjects affected / exposed 33 / 38 (86.84%)      occurrences all number 184 Alopecia      subjects affected / exposed 6 / 38 (15.79%)      occurrences all number 6 Musculoskeletal and connective tissue disorders Myalgia      subjects affected / exposed 5 / 38 (13.16%)      occurrences all number 12 Arthralgia      subjects affected / exposed 4 / 38 (10.53%)      occurrences all number 8 Infections and infestations infection      subjects affected / exposed 2 / 38 (5.26%)      occurrences all number 3 Metabolism and nutrition disorders Anorexia      subjects affected / exposed 24 / 38 (63.16%)      occurrences all number 91

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.
recruitment goal not reached
Online references
http://www.ncbi.nlm.nih.gov/pubmed/30544058

More information Top of page