Plain English Summary
Trial website
Additional identifiers
EudraCT number
2010-019602-16
ClinicalTrials.gov number
Protocol/serial number
9848
Study information
Scientific title
A study of Lapatinib in combination with oxaliplatin and capecitabine in Early HER-2 overexpressing Oesophageal and gastric cancers
Acronym
LEO
Study hypothesis
This study will test whether the ex vivo molecular response on a pre-treatment biopsy can predict the molecular response on a biopsy taken after 10 days of treatment with lapatinib. The study will also report observations of patterns of radiological, functional imaging and pathological response associated with molecular response
Ethics approval
South West 3 REC, 26/10/2010, 10/H0106/73
Study design
Non-randomised, interventional, observational qualitative trial
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Other
Trial type
Treatment
Patient information sheet
No participant information sheet available
Condition
Upper Gastro-Intestinal Cancer; Oesophagus, Stomach
Intervention
1. All 25 patients will be treated with lapatinib, there is no control arm
2. Fresh biopsies will be taken prior to lapatinib treatment start and 10 days post treatment start
3. All patients will have blood tests and renal function assessment prior to study entry and then after 31, 52 and 72 days of treatment
4. Treatment with lapatinib, oxaliplatin and capecitabine
5. All patients have a CT scan of thorax and abdomen prior to therapy and then another one after 3 cycles of chemotherapy for tumour assessmnet
6. All patient undergo a baseline whole body FDG-PET/CT examination at study entry and then 10 days after start of lapatinib therapy
7. Follow up length: 24 month(s)
8. Study entry : registration only
Intervention type
Other
Phase
Phase IV
Drug names
Primary outcome measure
1. Molecular response
2. Timepoint(s): 10 days post treatment with lapatinib
Secondary outcome measures
1. FDG PET response timepoint(s): 10 days post treatment with lapatinib
2. Objective radiological response timepoint(s): 72 days post treatment
3. Pathological complete response timepoint(s): 102 days post treatment
Overall trial start date
31/03/2010
Overall trial end date
31/07/2015
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Histologically confirmed gastric or oesophageal adenocarcinoma
2. Human Epidermal growth factor Receptor 2 (HER-2) 3+ on IHC OR HER-2 2+ on IHC but shown to have HER-2 amplification by (Fluorescent In-Situ Hybridization) FISH
3. Decision to treat with curative intent
4. Deemed to require chemotherapy prior to surgery using standard management algorithms
5. Ability to swallow oral medication
6. Baseline 18FDG PET/CT scan showing no evidence of distant metastases
7. Adequate haematological parameters: ANC = 1.0 x 109/L; WBC = 3.0 x 109/L; Plt = 100 x 109/L; haemoglobin (Hb) = 9g/dL (can be post-transfusion)
8. Adequate renal function (Measured or calculated creatinine clearance = 60 ml/min- if calculated the Cockcroft-Gault equation (Appendix A) to be used
9. Adequate liver function: serum Bilirubin = 1.5 x ULN; ALT/AST = 1.5 x ULN; ALP = 2.5 x ULN
10. Age >18 years
11. Women of child bearing potential using medically approved contraception (Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential)
12. Male patients using barrier contraceptives during the trial and for 6 months after the completion of the trial
13. Target gender: male & female
14. Lower age limit 18 years
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
UK Sample Size: 25
Participant exclusion criteria
1. Advanced disease not amenable to surgery
2. Previous diagnosis of malignancy (excluding adequately treated Cervical carcinoma in situ or Basal cell carcinoma of the skin)
3. Abnormal Cardiac function (LVEF below normal as measured by echocardiogram or MUGA scan)
4. History of clinically significant cardiac disease e.g. symptomatic coronary artery disease, uncontrolled cardiac dysrhythmia or myocardial infarction within the last 12 months)
5. History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan
6. Known peripheral neuropathy >Grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible)
7. Inability to give informed consent
8. Hypersensitivity to lapatinib or oxaliplatin or capecitabine
9. Prior treatment with chemotherapy or lapatinib or other specific anticancer therapy
10. Squamous cell carcinomas, unclear differentiation type, sarcomas, carcinoid or GIST
11. Known positive tests for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic active hepatitis B infection
12. Pregnancy/breastfeeding
13. Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
14. Treatment with another investigational agent within 30 days of commencing study treatment
15. Known or suspected dihydropyrimidine dehydrogenase deficiency (DPD)
16. Galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
Recruitment start date
17/06/2011
Recruitment end date
16/10/2013
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Addenbrooke's Hospital
Cambridge
CB2 0QQ
United Kingdom
Trial participating centre
University College London Hospital
235 Euston Road
London
NW1 2BU
United Kingdom
Funders
Funder type
Industry
Funder name
GlaxoSmithKline
Alternative name(s)
GlaxoSmithKline plc., GSK
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United Kingdom
Results and Publications
Publication and dissemination plan
To be confirmed at a later date
IPD sharing statement
The protocol has not specified these data sharing requirements, and patients have not consented to data sharing (recruited from 2011–2013) therefore this is not applicable. The trial is currently in the process of being archived.
Intention to publish date
Participant level data
Not expected to be available
Basic results (scientific)
Publication list
2015 results in https://www.ncbi.nlm.nih.gov/pubmed/26484410