Clinical Trial Results:
A study of lapatinib in combination with oxaliplatin and capecitabine in early HER-2 overexpressing oesophageal and gastric cancers.
Summary
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EudraCT number |
2010-019602-16 |
Trial protocol |
GB |
Global end of trial date |
26 Mar 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Jul 2016
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First version publication date |
30 Jul 2015
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Other versions |
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 |
N/A
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Cambridge University Hospitals NHS Foundation Trust
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Sponsor organisation address |
Hills Road, Cambridge University Hospitals NHS Foundation Trus, United Kingdom, CB2 0QQ
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Public contact |
Prasanna Kapilan, Cambridge clinical trials unit (CCTU)
, +44 1223 216524, Prasanna.kapilan@addenbrookes.nhs.uk
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Scientific contact |
Hugo Ford, Cambridge University Hospitals NHS Foundation Trust
, +44 1223 216524, hugo.ford@addenbrookes.nhs.uk
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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 |
14 Oct 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
18 Sep 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
26 Mar 2015
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
"Assess ability of ex vivo molecular response to predict molecular response on a biopsy after 10 days of treatment with lapatinib, and to report observations of patterns of radiological, functional imaging and pathological response associated with molecular response"
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Protection of trial subjects |
"Additional visits for investigations no risks. Where possible tests will be scheduled on the same day to minimise inconvenience.
Additional endoscopy: Minimal risk. Where possible pretreatment research biopsies will be obtained at a routine endoscopy visit rather than at an additional visit. The day 10 endoscopy is unavoidable.
Radiation risk from additional PET/CT scan: There is a small additional risk of second malignancy from the PET/CT scan and from MUGA scan if required. This is unavoidable but patients will be fully informed in the information sheet
Toxicity from Lapatinib: The main potential side effects from lapatinib are diarrhoea, skin rash and heart toxicity.
Diarrhoea and rash are normally easily managed without great distress to the patient. Heart toxicity is rare, but to
minimise the chance of it being a problem we will be monitoring heart function throughtout treatment with
echocardiograms. Although these tests involve an additional hospital visit they are noninvasive
and should not cause any discomfort or distress. In addition we have modified the standard chemotherapy to minimise the risk of toxicity of the combination of lapatinib with standard treatment. This involves omitting one drug (epirubicin) which is known to also damage heart tissue, and reducing the dose of capecitabine.
This combination at these doses has already been tested in gastric cancer and has been found to be safe and
effective, but to ensure patient safety we are performing a formal safety analysis after 6 patients have been recruited to ensure there is no need for further modifications."
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
24 May 2011
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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 |
United Kingdom: 10
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Worldwide total number of subjects |
10
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EEA total number of subjects |
10
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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) |
6
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From 65 to 84 years |
4
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85 years and over |
0
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Recruitment
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Recruitment details |
1st patient registered 05/07/2011, last patient registered 15/04/2013. Patients were recruited from two English sites in the patients' oncology clinics. | ||||||||||||||||
Pre-assignment
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Screening details |
Patients underwent pre-treatment Oesophago-gastro-duodenoscopy (OGD) and biopsy. | ||||||||||||||||
Pre-assignment period milestones
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Number of subjects started |
187 [1] | ||||||||||||||||
Number of subjects completed |
10 | ||||||||||||||||
Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Consent withdrawn by subject: 9 | ||||||||||||||||
Reason: Number of subjects |
Not meeting inclusion criteria as HER2 negative: 134 | ||||||||||||||||
Reason: Number of subjects |
Not meeting inclusion criteria - other reasons (20: 34 | ||||||||||||||||
Notes [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 187 patients assessed for eligibility and 177 patients excluded, so 10 patients enrolled for protocol treatment. |
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Period 1
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Period 1 title |
On-Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
Arms
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Arm title
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All patients | ||||||||||||||||
Arm description |
All registered subjects, planned to receive lapatinib in combination with oxaliplatin & capecitabine. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Oxaliplatin
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Investigational medicinal product code |
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Other name |
Eloxatin
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
"130 mg/m2 IV in 250-500 ml of 5% glucose over 2 hours (given once every 21
days for three cycles starting on day 11 of the trial)"
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Investigational medicinal product name |
capecitabine
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Investigational medicinal product code |
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Other name |
Xeloda
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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 |
850mg/m2 b.i.d po for 14 days.
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Investigational medicinal product name |
850mg/m2 b.i.d po for 14 days
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Investigational medicinal product code |
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Other name |
Tyverb
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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 |
1250 mg od po for days 1-72
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Baseline characteristics reporting groups
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Reporting group title |
On-Study
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
All patients
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Reporting group description |
All registered subjects, planned to receive lapatinib in combination with oxaliplatin & capecitabine. | ||
Subject analysis set title |
All
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All registered subjects, planned to receive lapatinib in combination with oxaliplatin & capecitabine.
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End point title |
Molecular response [1] | |||||||||||||||
End point description |
Concordance between molecular response in biopsies taken pre treatment and treated with lapatinib ex vivo and molecular response in a biopsy taken after 10 days of oral lapatinib in vivo (based on P-HER-2 staining on IHC only)
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End point type |
Primary
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End point timeframe |
From pre-treatment to 10 days post-treatment with lapatinib
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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: This is a single arm study. The summary of primary endpoints are provided. |
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Attachments |
LEO SAE Listing |
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No statistical analyses for this end point |
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End point title |
Response on FGD-PET (SUV Max) | ||||||||||
End point description |
Perecentage of responders on FDG-PET based on reduction of >35% in Standard Uptake Variable (SUV) Maximal from central review .
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End point type |
Secondary
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End point timeframe |
Please provide the time frame: it is requied for the end point definition.
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No statistical analyses for this end point |
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End point title |
Response on FGD-PET (SUV Average) | ||||||||||
End point description |
Perecentage of responders on FDG-PET based on reduction of >35% in Standard Uptake Variable (SUV) Average from central review.
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End point type |
Secondary
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End point timeframe |
Please provide the time frame: it is requied for the end point definition
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No statistical analyses for this end point |
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End point title |
Objective Radiological Response | ||||||||||
End point description |
Objective Radiological Response by RECIST crieteria - Percentage of responders.
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End point type |
Secondary
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End point timeframe |
Please provide the time frame: it is requied for the end point definition
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No statistical analyses for this end point |
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End point title |
R0 Resection | ||||||||||
End point description |
R0 Resection - Percentage of Responders.
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End point type |
Secondary
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End point timeframe |
Please provide the time frame: it is requied for the end point definition.
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No statistical analyses for this end point |
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End point title |
Pathological Complete Response | ||||||||||
End point description |
Pathological Complete Response - Percentage of Responders.
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End point type |
Secondary
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End point timeframe |
Please provide the time frame: it is requied for the end point definition.
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No statistical analyses for this end point |
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End point title |
Overall Survival | ||||||||||
End point description |
Overall Survival (months) - calculated from date of registration to date of death from any cause; suviving patients are censored at the date last known alive.
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End point type |
Secondary
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End point timeframe |
Please provide the time frame: it is requied for the end point definition.
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No statistical analyses for this end point |
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End point title |
Progression-Free Survival | ||||||||||
End point description |
Progression-Free Survival (months) - calculated from date of registration to date of first progression or date of death from any cause, whichever occurs first; surviving patients without disease progression are censored at the date last known alive.
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End point type |
Secondary
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End point timeframe |
Please provide the time frame: it is requied for the end point definition
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Date of patient registration onto the trial and continued until 21 days after the last study drug administration.
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Assessment type |
Systematic | ||
Dictionary used for adverse event reporting
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Dictionary name |
NCI CTC | ||
Dictionary version |
3
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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: Serious adverse events are reported in the file found in the uploaded attachment. |
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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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06 Apr 2011 |
Inclusion of standard statements regarding the submission of complaints from patients participating in clinical trials and clarification on compensation available to patients harmed during the trial. |
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10 Nov 2011 |
Addition of medication diary to help us to monitor medication compliance on the trial. |
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23 Mar 2012 |
change to exclusion criteria, dose modifications, additional blood test added and clarification of testing to be carried out on biopsies
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13 Sep 2012 |
Update the CTA to chnages the manufacturer responsible for the certification of the finished IMP and update the marketing authorisation number for Tyverb (lapatinib).
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11 Dec 2012 |
Changes to details regarding secondary objectives, dose modifications for Non‐Haematological toxicities, repeat biopsies, dose limiting toxicity, sample size and molecular testing on biopsies.
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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 |