A study of lapatinib in combination with oxaliplatin and capecitabine in oesophageal and gastric cancers

ISRCTN	ISRCTN49623344
DOI	https://doi.org/10.1186/ISRCTN49623344
EudraCT/CTIS number	2010-019602-16
Secondary identifying numbers	9848

Submission date: 27/05/2011
Registration date: 27/05/2011
Last edited: 25/10/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-lapatinib-with-chemotherapy-for-cancer-of-the-food-pipe-and-stomach-leo

Contact information

Dr Paula Kareclas
Scientific

Addenbrookes Hospital
Oncology Clinical Trials S4, Box 279
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Study information

Study design	Non-randomised, interventional, observational qualitative trial
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Other
Study type	Treatment
Participant information sheet	No participant information sheet available
Scientific title	A study of Lapatinib in combination with oxaliplatin and capecitabine in Early HER-2 overexpressing Oesophageal and gastric cancers
Study acronym	LEO
Study objectives	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(s)	South West 3 REC, 26/10/2010, 10/H0106/73
Health condition(s) or problem(s) studied	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
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 study start date	31/03/2010
Completion date	31/07/2015

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	UK Sample Size: 25
Total final enrolment	10
Key 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
Key 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
Date of first enrolment	17/06/2011
Date of final enrolment	16/10/2013

Locations

Countries of recruitment

England
United Kingdom

Study participating centres

Addenbrooke's Hospital

Cambridge
CB2 0QQ
United Kingdom

University College London Hospital

235 Euston Road
London
NW1 2BU
United Kingdom

Sponsor information

Cambridge University Hospitals NHS Foundation Trust (UK)
Hospital/treatment centre

Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom

"ROR"	https://ror.org/04v54gj93

Funders

Funder type

Industry

GlaxoSmithKline
Government organisation / For-profit companies (industry)

Alternative name(s): GlaxoSmithKline plc., GSK plc., GSK
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not expected to be made available
Publication and dissemination plan	To be confirmed at a later date
IPD sharing plan	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.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	03/11/2015		Yes	No
Plain English results			25/10/2022	No	Yes
HRA research summary			28/06/2023	No	No

Editorial Notes

25/10/2022: Cancer Research UK plain English results link and total final enrolment added.
04/05/2018: The following changes were made:
1. South West 3 REC was added as the ethics committee.
2. The overall trial start date was changed from 01/04/2011 to 31/03/2010.
3. The overall trial end date was changed from 16/11/2013 to 31/07/2015.
4. An IPD sharing statement has been added.
04/05/2018: Publication reference added.
19/01/2018: No publications found in PubMed, verifying study status with principal investigator.