Condition category
Cancer
Date applied
27/05/2011
Date assigned
27/05/2011
Last edited
29/09/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Paula Kareclas

ORCID ID

Contact details

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

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

First MREC approval date 26/10/2010 ref: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

Not available in web format, please use the contact details below to request a patient information sheet

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 measures

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

01/04/2011

Overall trial end date

16/11/2013

Reason abandoned

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

Sponsor information

Organisation

Cambridge University Hospitals NHS Foundation Trust (UK)

Sponsor details

Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Sponsor type

Hospital/treatment centre

Website

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

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes