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Lapatinib in Early Oesophageal Cancer (LEO)

Full Title of Study: LEO: A study of lapatinib in early oesophago-gastric cancer


Sample Size: 25 


Study Objectives: One of the most common problems in cancer therapy is that patients do not always benefit because their cancer is not responsive to the drugs. Oesophageal cancers (among other cancers) often overexpress EGFR and Her-2, two commonly known receptor tyrosine kinases which are implicated in (cancer) cell growth and division. Lapatinib is a small molecule tyrosine kinase inhibitor which targets active (phosphorylated) Her-2 and EGFR, resulting in cell death. However, not all patients would benefit from Lapatinib. The LEO trial aims to understand whether it is possible to predict the patient response to Lapatinib prior to treatment by tackling this problem from two angles: 1) By testing molecular indicators of response to therapy in Her-2 overexpressing oeseophageal adenocarinoma samples and 2) By performing in vitro assays of tissue responsiveness to the drug prior to therapy. 


Study Design: Open label phase Ib/phase IV study


Participating Centres:MRC Cancer Unit and Addenbrooke's Hospital Cambridge, UCL Cancer Institute and University College London Hospitals. 


Primary endpoints:

  • Molecular response (comparing pre- and post-treatment biopsies. Either reduction in score for Her-2 staining on immunohistochemistry by 2 or reduction in ratio of phosphorylated total protein by 50% on Duolink immunohistochemistry)


Secondary endpoints:

  • Objective radiological response
  • FDG PET response (reduction of >35% in Standard Uptake Value (SUV) in a 1.5cm ROI)
  • Pathological complete response
  • R0 resection
  • Survival


Patients - Inclusion criteria:

  • Histologically confirmed gastric or oesophageal adenocarcinoma
  • HER-2 overexpression on IHC or FISH
  • Decision to treat with curative intent
  • Deemed to require chemotherapy prior to surgery
  • Ability to swallow oral medication
  • Baseline 18FDG PET/CT scan showing no evidence of distant metastases
  • Adequate haematological, renal and hepatic function


Patients - Exclusion criteria:

  • Disease not amenable to surgery
  • Previous diagnosis of malignancy
  • Abnormal Cardiac function
  • Inability to give informed consent
  • Hypersensitivity to lapatinib
  • Prior treatment with chemotherapy or lapatinib
  • Squamous cell carcinomas, unclear differentiation type,sarcomas, carcinoid or GIST
  • Pregnancy/breastfeeding
  • Current active hepatic or biliary disease


Investigational medicinal product and dosage:
Lapatinib 1250mg (oral, tablet)
Oxaliplatin 130mg/m2 (intravenously for 3 weeks)
Capecitabine 1700mg/m2/day days 1-14 


Status of the study: Recruiting. 


PortfolioThe study has been adopted into the UKCRN portfolio (study ID 9848).


LEO Group:

  • HER Ford (Chief Investigator, Cambridge)
  • RC Fitzgerald (Scientific Lead, Cambridge)
  • P Kareclas (Trial Coordinator, Cambridge)
  • LKE Schulz (PhD Student, Cambridge)
  • M Barbera (Postdoctoral Research Fellow, Cambridge)
  • L Mills (Research Nurse, Cambridge)
  • M O’Donovan (Consultant Pathologist, Cambridge)
  • S Bond (Database Design and Statistician, Cambridge)
  • B Haynes (Tissue Bank Manager, Cambridge)
  • B Spencer (Research Endoscopy Staff, Cambridge)
  • D Hochhauser  (Principal Investigator, London)
  • L Lovat (Academic Collaborator, London)
  • M Novelli (Consultant Pathologist, London)



GlaxoSmithKline (Investigator Led Industry Sponsored)


CLRN via UKCRN portfolio