Clinical trials in upper gastro-intestinal and gastric cancer

Lead Research Organisation: MRC Clinical Trials Unit

Abstract

Together both oesophageal and stomach cancer cause approximately 13,000 deaths each year in the UK. At the time of diagnosis, if the cancer appears confined to the stomach or oesophagus then surgery is performed aiming to remove all the tumour. Unfortunately the chance of being alive 5 years after such an operation is in the region of 20-30%. Therefore an urgent need to improve outcomes in this disease is required.|The potential advantages of combining chemotherapy (drug treatment) with surgery are (i) chemotherapy before the operation may cause the tumour to shrink making it easier for the surgeon to remove it. (ii) chemotherapy after the operation may kill any cancer cells (micrometastases) that have not been removed at surgery (iii) chemotherapy may kill cancer cells that have spread away from the stomach or oesophagus but are too small to be detected with current imaging scans.|In oesophageal cancer we have performed a randomised trial of 802 patients (OEO2 Trial). Patients received either surgery alone or 2 cycles of chemotherapy before surgery. Overall survival was significantly increased in the patients allocated chemotherapy. Following on from this we are now conducting a trial to see if 4 cycles of a newer chemotherapy regimen before surgery will improve survival rates even further.|In stomach cancer we performed a randomised trial of 503 patients (MAGIC Trial). Patients received either surgery or 3 cycles of chemotherapy before and after their operation. Overall survival was significantly increased in the patients in the chemotherapy group. Following on from this we are undertaking a trial assessing the effect of adding a new treatment that affects the blood supply of tumours, and therefore their growth, to the chemotherapy treatment that is given before and after surgery. We are hopeful that this will improve survival rates even further.

Technical Summary

Oesophagogastric cancers cause approximately 13,000 deaths per year in the UK, or 6% of all cancer deaths. The outlook is poor, with only 20 to 30% of patients who undergo potentially curative surgery alive 2 years later. There is therefore a great need to improve outcomes. |In patients with operable oesophageal cancer, OE02 compared surgical resection with or without two pre-operative cycles of cisplatin and fluorouracil (CF). 802 patients were randomised, making this the largest randomised trial ever conducted in this disease. The results, originally reported in 2002 (Lancet 2002, 359: 1727-1733) and updated in 2008 (J. Clin. Oncol) show that with pre-operative chemotherapy survival is prolonged and is now standard treatment in the UK. The trial attracted great interest internationally, not least because a similar, but substantially smaller American trial showed no advantage with chemotherapy. Both trials contributed to an individual patient data meta-analysis of all relevant trials and this confirmed a significant survival benefit to pre-operative chemotherapy.|Building on the success of OEO2 we are currently undertaking a randomised trial (OEO5) where patients either receive 2 cycles of CF chemotherapy followed by surgery or 4 cycles of ECX chemotherapy followed by surgery. The trial is on target to complete accrual of 842 patients in early 2011.|In patients with operable gastric cancer, the ST02 randomised trial, or MRC Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial, compared surgical resection with or without peri-operative chemotherapy using a regimen of epirubicin and cisplatin with 5-fluorouracil by continuous infusion (3 cycles pre-operatively and 3 post-operatively.) 503 patients were randomised, and peri-operative chemotherapy was shown to significantly improve survival (HR for death 0.75 95%CI 0.6-0.93 p=0.009) with 5 year survival rates increased from 23% to 36% (N Engl J Med. 2006 Jul 6; 355(1):11-20).|Again building on this success ST03 is a phase II/III trial randomised trial where patients are randomized to 3 pre- and 3 post-operative cycles of ECX and surgery with or without bevacizumab, a monoclonal antibody against the vascular endothelial growth factor receptor. It is intended that this will be an international trial recruiting in the region of 1000 patients. Phase II recruitment is complete. |For all of these trials additional translational studies will be performed on tissue samples with the aim of identifying prognostic and predictive factors that identify patients likely to respond to these treatments.

Publications

10 25 50

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Allum WH (2009) Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. in Journal of clinical oncology : official journal of the American Society of Clinical Oncology

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Cunningham D (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. in The New England journal of medicine

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Okines AF (2013) Biomarker analysis in oesophagogastric cancer: Results from the REAL3 and TransMAGIC trials. in European journal of cancer (Oxford, England : 1990)

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Okines AF (2013) Effect of HER2 on prognosis and benefit from peri-operative chemotherapy in early oesophago-gastric adenocarcinoma in the MAGIC trial. in Annals of oncology : official journal of the European Society for Medical Oncology

 
Guideline Title Gastric cancer: ESMO-ESSO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up
Description ESMO guidelines for gastric cancer
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
Impact The ST02 trial demonstrated significant survival benefits from peri-operative chemotherapy, leading to its citation in these and other clinical guidelines. This has extended the awareness and impact of the trial internationally.
URL http://www.esmo.org/Guidelines/Gastrointestinal-Cancers/Gastric-Cancer
 
Guideline Title Oesophageal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up
Description ESMO guidelines for oesophageal cancer
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
Impact Pre-operative chemotherapy, demonstrated to improve survival by the OE02 trial,is a recommended option in these treatment guidelines, extending the impact of the trial results.
URL http://www.esmo.org/Guidelines/Gastrointestinal-Cancers/Oesophageal-Cancer
 
Guideline Title Management of Oesophageal and Gastric Cancer
Description OE02 SIGN guidance
Geographic Reach Europe 
Policy Influence Type Citation in clinical guidelines
Impact Dissemintation of trial results (showing improved survival following pre-operative chemotherapy) and incorporation into standard practice
URL http://www.sign.ac.uk/pdf/sign87.pdf
 
Description ST02 NCI PDQ standard treatment option
Geographic Reach North America 
Policy Influence Type Citation in clinical reviews
Impact Cited in the National Cancer Institute PDQ treatment option overview as evidence for perioperative chemotherapy as a standard treatment option
 
Guideline Title SIGN Guidelines for the management of oesophageal and gastric cancer
Description ST02 SIGN guidance
Geographic Reach National 
Policy Influence Type Citation in clinical guidelines
Impact Cites the ST02 trial results supporting peri-operative chemotherapy as standard of care for operable gastric and junctional cancers; this was shown to improve survival and therefore impacts directly on patient outcome.
URL http://www.bsg.org.uk/clinical-guidelines/gastroduodenal/guidelines-for-the-management-of-oesophagea...
 
Description Upper GI meta analysis
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in systematic reviews
 
Description CRUK funding (OEO5 Trial)
Amount £750,000 (GBP)
Funding ID C1495/A3005 and C7497/A12373 
Organisation Cancer Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2010 
End 10/2012
 
Description CRUK funding (ST03 Trial)
Amount £760,000 (GBP)
Funding ID C1504/A6410 
Organisation Cancer Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start  
End 12/2013
 
Title OE02 trial database 
Description Data collected specifically to allow monitoring and analysis of the primary research question addressed by the OE02 trial. The database also includes data relevant not only to the primary question, but which provides a unique resource with which to address related questions. External groups may request access to the data through the independent Trial Steering Committee 
Type Of Material Improvements to research infrastructure 
Year Produced 2007 
Provided To Others? Yes  
Impact Analysis of the OE02 trial and dissemination of the results, demonstrating improved survival with pre-operative chemotherapy. 
 
Title ST02 trial database 
Description Data collected specifically to allow monitoring and analysis of the primary research question addressed by the ST02 trial. The database also includes data relevant not only to the primary question, but which provides a unique resource with which to address related questions. External groups may request access to the data through the independent Trial Steering Committee 
Type Of Material Improvements to research infrastructure 
Provided To Others? No  
Impact Analysis of the ST02 trial and dissemination of the results which showed improved survival with the use of peri-operative chemotherapy. 
 
Title TransST03 sample collection 
Description Blood samples and tumour samples from pre-treatment biopsies and resected specimens from patients in the ST03 trial who consented to participant in the translational component of the trial. 
Type Of Material Biological samples 
Provided To Others? No  
Impact Collection of samples is ongoing. 
 
Title trans Oe02 sample collection 
Description tumour samples from pre-treatment biopsies and resection specimens from patients randomised into the OE02 trial 
Type Of Material Biological samples 
Provided To Others? No  
Impact Sample collection completed in 2011, analyses ongoing of potential predictive and prognostic biomarkers. 
 
Title trans ST02 sample collection 
Description tumour samples from pre treatment biopsies and resection specimens from patients randomised into the ST02 trial 
Type Of Material Biological samples 
Provided To Others? No  
Impact Collection was completed in 2011. Analysis of potential predictive and prognostic biomarkers is ongoing but to date has yielded one publication in press with a second submitted. 
 
Description OE02 trial 
Organisation Gustave-Roussy Institute
Department Meta Analysis Unit Gustave-Roussy
Country France 
Sector Multiple 
PI Contribution Design, conduct and analysis of the OE02 trial, integration of clinical data with biomaker data and analysis of combined dataset to determine potential prognostic or predictive biomarkers.
Collaborator Contribution This trial was a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and corresponding networks in the other UK nations which provided the infrastructure to support trials at the clinical sites.This collaboration includes all the staff at each of the clinical sites that have participated in the OE02 clinical trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. We collaborated with statisticians at the Institute Gustave Roussy on the design, conduct and analysis of an individual patient data meta-analysis of trials of peri-operative chemotherapy in oesophageal cancer, to which we also provided trial data. Histopathologists at the University of Leeds provide oversight of retrospective tumour sample collection, and analysis of tumour samples with respect to predefined potential prognostic and/or predictive biomarkers, some of the sample analysis has also been carried out with collaborators in Singapore; we are linking these data to the clinical outcomes of trial patients in order to assess the potential markers.
Impact The trial results were updated and published in 2009; in addition, the earlier trial results contributed to an individual patient data meta analysis which was presented in abstract form in 2007 and is currently being updated to included the updated OE02 data. This was a multidisciplinary collaboration comprising clinicians (oncologists and surgeons) and research nurses at participating sites, laboratory scientists and histopathologists analysing tumour samples in the central labs, and statisticians and operational staff at the Clinical Trials Unit.
 
Description OE02 trial 
Organisation National Cancer Research Institute (NCRI)
Department National Cancer Research Network (NCRN)
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Design, conduct and analysis of the OE02 trial, integration of clinical data with biomaker data and analysis of combined dataset to determine potential prognostic or predictive biomarkers.
Collaborator Contribution This trial was a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and corresponding networks in the other UK nations which provided the infrastructure to support trials at the clinical sites.This collaboration includes all the staff at each of the clinical sites that have participated in the OE02 clinical trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. We collaborated with statisticians at the Institute Gustave Roussy on the design, conduct and analysis of an individual patient data meta-analysis of trials of peri-operative chemotherapy in oesophageal cancer, to which we also provided trial data. Histopathologists at the University of Leeds provide oversight of retrospective tumour sample collection, and analysis of tumour samples with respect to predefined potential prognostic and/or predictive biomarkers, some of the sample analysis has also been carried out with collaborators in Singapore; we are linking these data to the clinical outcomes of trial patients in order to assess the potential markers.
Impact The trial results were updated and published in 2009; in addition, the earlier trial results contributed to an individual patient data meta analysis which was presented in abstract form in 2007 and is currently being updated to included the updated OE02 data. This was a multidisciplinary collaboration comprising clinicians (oncologists and surgeons) and research nurses at participating sites, laboratory scientists and histopathologists analysing tumour samples in the central labs, and statisticians and operational staff at the Clinical Trials Unit.
 
Description OE02 trial 
Organisation National University of Singapore
Department Cancer Science Institute of Singapore (CSI)
Country Singapore 
Sector Academic/University 
PI Contribution Design, conduct and analysis of the OE02 trial, integration of clinical data with biomaker data and analysis of combined dataset to determine potential prognostic or predictive biomarkers.
Collaborator Contribution This trial was a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and corresponding networks in the other UK nations which provided the infrastructure to support trials at the clinical sites.This collaboration includes all the staff at each of the clinical sites that have participated in the OE02 clinical trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. We collaborated with statisticians at the Institute Gustave Roussy on the design, conduct and analysis of an individual patient data meta-analysis of trials of peri-operative chemotherapy in oesophageal cancer, to which we also provided trial data. Histopathologists at the University of Leeds provide oversight of retrospective tumour sample collection, and analysis of tumour samples with respect to predefined potential prognostic and/or predictive biomarkers, some of the sample analysis has also been carried out with collaborators in Singapore; we are linking these data to the clinical outcomes of trial patients in order to assess the potential markers.
Impact The trial results were updated and published in 2009; in addition, the earlier trial results contributed to an individual patient data meta analysis which was presented in abstract form in 2007 and is currently being updated to included the updated OE02 data. This was a multidisciplinary collaboration comprising clinicians (oncologists and surgeons) and research nurses at participating sites, laboratory scientists and histopathologists analysing tumour samples in the central labs, and statisticians and operational staff at the Clinical Trials Unit.
 
Description OE02 trial 
Organisation University of Leeds
Department Faculty of Medicine and Health
Country United Kingdom 
Sector Academic/University 
PI Contribution Design, conduct and analysis of the OE02 trial, integration of clinical data with biomaker data and analysis of combined dataset to determine potential prognostic or predictive biomarkers.
Collaborator Contribution This trial was a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and corresponding networks in the other UK nations which provided the infrastructure to support trials at the clinical sites.This collaboration includes all the staff at each of the clinical sites that have participated in the OE02 clinical trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. We collaborated with statisticians at the Institute Gustave Roussy on the design, conduct and analysis of an individual patient data meta-analysis of trials of peri-operative chemotherapy in oesophageal cancer, to which we also provided trial data. Histopathologists at the University of Leeds provide oversight of retrospective tumour sample collection, and analysis of tumour samples with respect to predefined potential prognostic and/or predictive biomarkers, some of the sample analysis has also been carried out with collaborators in Singapore; we are linking these data to the clinical outcomes of trial patients in order to assess the potential markers.
Impact The trial results were updated and published in 2009; in addition, the earlier trial results contributed to an individual patient data meta analysis which was presented in abstract form in 2007 and is currently being updated to included the updated OE02 data. This was a multidisciplinary collaboration comprising clinicians (oncologists and surgeons) and research nurses at participating sites, laboratory scientists and histopathologists analysing tumour samples in the central labs, and statisticians and operational staff at the Clinical Trials Unit.
 
Description OEO5 Trial 
Organisation Cancer Research UK
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Design, conduct and analysis of the trial
Collaborator Contribution This trial is a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and corresponding networks in the other UK nations, and specifically includes all the staff at each of the clinical sites that have participated in the OEO5 clinical trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. The NCRI Clinical Studies group supported the set up and promotes participation into the trial. Collaborating pathologists in Leeds collect, store and subsequently analyse blood and pathology samples from participants in this trial. Roche provide free study drug, capecitabine. CRUK funded the trial and also ensured inclusion of trial information in the CR UK cancer help database, accessible by potential patients and other members of the public
Impact The trial completed accrual in November 2011. Ongoing contibution to the unique clinical trial database This is a multidisciplinary collaboration, comprising surgeons, oncologists, pathologists and research nurses in participating hospitals, together with statisticians and operational staff at the CTU.
 
Description OEO5 Trial 
Organisation F. Hoffmann-La Roche AG
Country Global 
Sector Private 
PI Contribution Design, conduct and analysis of the trial
Collaborator Contribution This trial is a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and corresponding networks in the other UK nations, and specifically includes all the staff at each of the clinical sites that have participated in the OEO5 clinical trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. The NCRI Clinical Studies group supported the set up and promotes participation into the trial. Collaborating pathologists in Leeds collect, store and subsequently analyse blood and pathology samples from participants in this trial. Roche provide free study drug, capecitabine. CRUK funded the trial and also ensured inclusion of trial information in the CR UK cancer help database, accessible by potential patients and other members of the public
Impact The trial completed accrual in November 2011. Ongoing contibution to the unique clinical trial database This is a multidisciplinary collaboration, comprising surgeons, oncologists, pathologists and research nurses in participating hospitals, together with statisticians and operational staff at the CTU.
 
Description OEO5 Trial 
Organisation National Cancer Research Institute (NCRI)
Department NCRI Upper Gastrointestinal Cancer CSG
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Design, conduct and analysis of the trial
Collaborator Contribution This trial is a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and corresponding networks in the other UK nations, and specifically includes all the staff at each of the clinical sites that have participated in the OEO5 clinical trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. The NCRI Clinical Studies group supported the set up and promotes participation into the trial. Collaborating pathologists in Leeds collect, store and subsequently analyse blood and pathology samples from participants in this trial. Roche provide free study drug, capecitabine. CRUK funded the trial and also ensured inclusion of trial information in the CR UK cancer help database, accessible by potential patients and other members of the public
Impact The trial completed accrual in November 2011. Ongoing contibution to the unique clinical trial database This is a multidisciplinary collaboration, comprising surgeons, oncologists, pathologists and research nurses in participating hospitals, together with statisticians and operational staff at the CTU.
 
Description OEO5 Trial 
Organisation National Cancer Research Institute (NCRI)
Department National Cancer Research Network (NCRN)
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Design, conduct and analysis of the trial
Collaborator Contribution This trial is a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and corresponding networks in the other UK nations, and specifically includes all the staff at each of the clinical sites that have participated in the OEO5 clinical trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. The NCRI Clinical Studies group supported the set up and promotes participation into the trial. Collaborating pathologists in Leeds collect, store and subsequently analyse blood and pathology samples from participants in this trial. Roche provide free study drug, capecitabine. CRUK funded the trial and also ensured inclusion of trial information in the CR UK cancer help database, accessible by potential patients and other members of the public
Impact The trial completed accrual in November 2011. Ongoing contibution to the unique clinical trial database This is a multidisciplinary collaboration, comprising surgeons, oncologists, pathologists and research nurses in participating hospitals, together with statisticians and operational staff at the CTU.
 
Description OEO5 Trial 
Organisation University of Leeds
Department Leeds Institute of Molecular Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Design, conduct and analysis of the trial
Collaborator Contribution This trial is a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and corresponding networks in the other UK nations, and specifically includes all the staff at each of the clinical sites that have participated in the OEO5 clinical trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. The NCRI Clinical Studies group supported the set up and promotes participation into the trial. Collaborating pathologists in Leeds collect, store and subsequently analyse blood and pathology samples from participants in this trial. Roche provide free study drug, capecitabine. CRUK funded the trial and also ensured inclusion of trial information in the CR UK cancer help database, accessible by potential patients and other members of the public
Impact The trial completed accrual in November 2011. Ongoing contibution to the unique clinical trial database This is a multidisciplinary collaboration, comprising surgeons, oncologists, pathologists and research nurses in participating hospitals, together with statisticians and operational staff at the CTU.
 
Description ST02 (MAGIC) Trial 
Organisation Cambridge University Hospitals NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Design, conduct and analysis of the clinical trial; linkage of genetic marker data with clinical outcome data to assess the potential prognostic and predictive value of the markers examined
Collaborator Contribution This trial was a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and corresponding networks in the other UK nations, which provided the infrastructure to support the conduct of the trial at the clinical sites.This collaboration includes all the staff at each of the clinical sites that have participated in the ST02 trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. Colleagues at the Royal Marsden Hospital over saw retrospective collection of tumour samples from patients in the ST02 trial, carried out central review and laboratory analysis of potential biomarkers. Further markers were assessed by colleagues at the National University of Singapore.
Impact The major output was the publication of the trial results in the New England Journal of Medicine in 2006. Compilation of tissue sample collection was completed in 2011 and several analyses were completed in 2012, with one paper in press and another submitted. This was a multidisciplinary collaboration, comprising clinicians and research nurses in participating hospitals, laboratory scientists and pathologists analysing tumour sample data together with statisticians and operational staff at the CTU.
 
Description ST02 (MAGIC) Trial 
Organisation Genetech, Inc
Country United States 
Sector Private 
PI Contribution Design, conduct and analysis of the clinical trial; linkage of genetic marker data with clinical outcome data to assess the potential prognostic and predictive value of the markers examined
Collaborator Contribution This trial was a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and corresponding networks in the other UK nations, which provided the infrastructure to support the conduct of the trial at the clinical sites.This collaboration includes all the staff at each of the clinical sites that have participated in the ST02 trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. Colleagues at the Royal Marsden Hospital over saw retrospective collection of tumour samples from patients in the ST02 trial, carried out central review and laboratory analysis of potential biomarkers. Further markers were assessed by colleagues at the National University of Singapore.
Impact The major output was the publication of the trial results in the New England Journal of Medicine in 2006. Compilation of tissue sample collection was completed in 2011 and several analyses were completed in 2012, with one paper in press and another submitted. This was a multidisciplinary collaboration, comprising clinicians and research nurses in participating hospitals, laboratory scientists and pathologists analysing tumour sample data together with statisticians and operational staff at the CTU.
 
Description ST02 (MAGIC) Trial 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Design, conduct and analysis of the clinical trial; linkage of genetic marker data with clinical outcome data to assess the potential prognostic and predictive value of the markers examined
Collaborator Contribution This trial was a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and corresponding networks in the other UK nations, which provided the infrastructure to support the conduct of the trial at the clinical sites.This collaboration includes all the staff at each of the clinical sites that have participated in the ST02 trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. Colleagues at the Royal Marsden Hospital over saw retrospective collection of tumour samples from patients in the ST02 trial, carried out central review and laboratory analysis of potential biomarkers. Further markers were assessed by colleagues at the National University of Singapore.
Impact The major output was the publication of the trial results in the New England Journal of Medicine in 2006. Compilation of tissue sample collection was completed in 2011 and several analyses were completed in 2012, with one paper in press and another submitted. This was a multidisciplinary collaboration, comprising clinicians and research nurses in participating hospitals, laboratory scientists and pathologists analysing tumour sample data together with statisticians and operational staff at the CTU.
 
Description ST02 (MAGIC) Trial 
Organisation National Cancer Research Institute (NCRI)
Department National Cancer Research Network (NCRN)
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Design, conduct and analysis of the clinical trial; linkage of genetic marker data with clinical outcome data to assess the potential prognostic and predictive value of the markers examined
Collaborator Contribution This trial was a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and corresponding networks in the other UK nations, which provided the infrastructure to support the conduct of the trial at the clinical sites.This collaboration includes all the staff at each of the clinical sites that have participated in the ST02 trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. Colleagues at the Royal Marsden Hospital over saw retrospective collection of tumour samples from patients in the ST02 trial, carried out central review and laboratory analysis of potential biomarkers. Further markers were assessed by colleagues at the National University of Singapore.
Impact The major output was the publication of the trial results in the New England Journal of Medicine in 2006. Compilation of tissue sample collection was completed in 2011 and several analyses were completed in 2012, with one paper in press and another submitted. This was a multidisciplinary collaboration, comprising clinicians and research nurses in participating hospitals, laboratory scientists and pathologists analysing tumour sample data together with statisticians and operational staff at the CTU.
 
Description ST02 (MAGIC) Trial 
Organisation National University of Singapore
Department Cancer Science Institute of Singapore (CSI)
Country Singapore 
Sector Academic/University 
PI Contribution Design, conduct and analysis of the clinical trial; linkage of genetic marker data with clinical outcome data to assess the potential prognostic and predictive value of the markers examined
Collaborator Contribution This trial was a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and corresponding networks in the other UK nations, which provided the infrastructure to support the conduct of the trial at the clinical sites.This collaboration includes all the staff at each of the clinical sites that have participated in the ST02 trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. Colleagues at the Royal Marsden Hospital over saw retrospective collection of tumour samples from patients in the ST02 trial, carried out central review and laboratory analysis of potential biomarkers. Further markers were assessed by colleagues at the National University of Singapore.
Impact The major output was the publication of the trial results in the New England Journal of Medicine in 2006. Compilation of tissue sample collection was completed in 2011 and several analyses were completed in 2012, with one paper in press and another submitted. This was a multidisciplinary collaboration, comprising clinicians and research nurses in participating hospitals, laboratory scientists and pathologists analysing tumour sample data together with statisticians and operational staff at the CTU.
 
Description ST02 (MAGIC) Trial 
Organisation Poole Hospital NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Design, conduct and analysis of the clinical trial; linkage of genetic marker data with clinical outcome data to assess the potential prognostic and predictive value of the markers examined
Collaborator Contribution This trial was a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and corresponding networks in the other UK nations, which provided the infrastructure to support the conduct of the trial at the clinical sites.This collaboration includes all the staff at each of the clinical sites that have participated in the ST02 trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. Colleagues at the Royal Marsden Hospital over saw retrospective collection of tumour samples from patients in the ST02 trial, carried out central review and laboratory analysis of potential biomarkers. Further markers were assessed by colleagues at the National University of Singapore.
Impact The major output was the publication of the trial results in the New England Journal of Medicine in 2006. Compilation of tissue sample collection was completed in 2011 and several analyses were completed in 2012, with one paper in press and another submitted. This was a multidisciplinary collaboration, comprising clinicians and research nurses in participating hospitals, laboratory scientists and pathologists analysing tumour sample data together with statisticians and operational staff at the CTU.
 
Description ST02 (MAGIC) Trial 
Organisation Royal Marsden NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Design, conduct and analysis of the clinical trial; linkage of genetic marker data with clinical outcome data to assess the potential prognostic and predictive value of the markers examined
Collaborator Contribution This trial was a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and corresponding networks in the other UK nations, which provided the infrastructure to support the conduct of the trial at the clinical sites.This collaboration includes all the staff at each of the clinical sites that have participated in the ST02 trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. Colleagues at the Royal Marsden Hospital over saw retrospective collection of tumour samples from patients in the ST02 trial, carried out central review and laboratory analysis of potential biomarkers. Further markers were assessed by colleagues at the National University of Singapore.
Impact The major output was the publication of the trial results in the New England Journal of Medicine in 2006. Compilation of tissue sample collection was completed in 2011 and several analyses were completed in 2012, with one paper in press and another submitted. This was a multidisciplinary collaboration, comprising clinicians and research nurses in participating hospitals, laboratory scientists and pathologists analysing tumour sample data together with statisticians and operational staff at the CTU.
 
Description ST02 (MAGIC) Trial 
Organisation University of Leeds
Department Leeds Institute of Cancer & Pathology
Country United Kingdom 
Sector Academic/University 
PI Contribution Design, conduct and analysis of the clinical trial; linkage of genetic marker data with clinical outcome data to assess the potential prognostic and predictive value of the markers examined
Collaborator Contribution This trial was a collaboration with the National Cancer Research Network (a component of NIHR and funded by the English Dept of Health) and corresponding networks in the other UK nations, which provided the infrastructure to support the conduct of the trial at the clinical sites.This collaboration includes all the staff at each of the clinical sites that have participated in the ST02 trial. Each site identified patients potentially suitable for the trial, sought informed consent, treated and followed-up patients within the trial and provided data through completion and return of case record forms. Colleagues at the Royal Marsden Hospital over saw retrospective collection of tumour samples from patients in the ST02 trial, carried out central review and laboratory analysis of potential biomarkers. Further markers were assessed by colleagues at the National University of Singapore.
Impact The major output was the publication of the trial results in the New England Journal of Medicine in 2006. Compilation of tissue sample collection was completed in 2011 and several analyses were completed in 2012, with one paper in press and another submitted. This was a multidisciplinary collaboration, comprising clinicians and research nurses in participating hospitals, laboratory scientists and pathologists analysing tumour sample data together with statisticians and operational staff at the CTU.
 
Title OE02 trial 
Description The OE02 trial results - updated in 2009 - were the first to clearly demonstrate improved survival through the addition of pre-operative chemotherapy with CF (cisplatin + 5fU) in the treatment of operable oesophageal cancer. The trial was funded by the MRC through the core funding of the MRC CTU. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Wide-scale adoption
Year Development Stage Completed 2009
Development Status Under active development/distribution
Clinical Trial? Yes
Impact First (and largest) trial to demonstrate improved survival through the use of pre-operative chemotherapy. This has become a standard treatment approach, cited in clinical guidelines, which has changed clinical practice. 
URL http://www.isrctn.com/ISRCTN43987580
 
Title OE05 trial 
Description A previous MRC trial, OE02, showed that pre-operative chemotherapy with cisplatin and 5FU improved survival in patients with operable oesophageal cancer. The OE05 trial attempts to build on this by assessing the impact on survival of replacing CF chemotherapy with ECX (epirubicin, cisplatin, capecitabine). The trial has completed accrual, follow-up continues prior to final analysis. The trial is funded by Cancer Research UK 
Type Therapeutic Intervention - Drug
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2006
Development Status Under active development/distribution
Clinical Trial? Yes
Impact none yet, trial results anticipated 2014/15 
URL http://www.isrctn.com/ISRCTN01852072
 
Title ST02 ECF 
Description The ECF chemotherapy combination, given pre and post-operatively, improves survival in operable gastric cancer. It now forms the backbone of treatment (with oral drug capecitabine replacing infusional drug fluorouracil) to which novel agents are being added, in the case of our ongoing ST03 trial the novel agents being bevacizumab (in patients with unknown or HER2-ve status) and lapatinib (in HER-2 +ve patients) 
Type Therapeutic Intervention - Drug
Current Stage Of Development Wide-scale adoption
Development Status Under active development/distribution
Clinical Trial? Yes
Impact The ST02 trial directly benefited the public by showing that peri-operative chemotherapy improved survival over surgery alone in patients with operable gastric cancer. This is now widely used as standard treatment, and forms the control arm of subsequent clinical trials. 
URL http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=645
 
Title ST03 trial - bevacizumab 
Description Bevacizumab is a monoclonal antibody against VEGF which has been shown to improve outcomes in a number of cancer types; ST03 trial evaluates the impact of adding bevacizumab to standard chemotherapy for operable gastroesophageal cancer. The final analysis has taken place. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2015
Development Status Closed
Clinical Trial? Yes
Impact Impact of trial still be to be assessed. 
URL http://www.isrctn.com/ISRCTN46020948
 
Title ST03 trial - lapatinib 
Description The anti-HER-2 monoclonal antibody, trastuzumab, has been shown to improve survival in HER-2 positive gastric cancer patients with metastatic disease. Lapatinib is an oral small molecule tyrosine kinase inhibitor targeting human epidermal growth factor receptor-1 (HER-1, most commonly called EGFR) and the human epidermal growth factor receptor-2 (HER-2, also known as c-erb B2/neu and ERBB2). This trial assesses the feasibility of incorporating HER-2 testing into the management of operable gastric cancer in a timely manner, and the safety of adding lapatinib to ECX chemotherapy in patients with HER-2 positive oesophagogastric cancers. This substudy to the ST03 trial is taking place in selected sites, and will establish the appropriate dose schedule of ECX+lapatinib to take forward into phase III evaluation. The ST03 trial is funded by Cancer Research UK with additional funding from GSK to support the lapatinib feasibilty study. The lapatinib feasibility substudy is close to its accrual target - recruitment continues. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2015
Development Status Under active development/distribution
Clinical Trial? Yes
Impact None yet - accrual ongoing. 
URL http://www.isrctn.com/ISRCTN46020948
 
Description OE05 ASCO PRESENTATION 2014 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Opportunities for discussion with others working in similar area

Maintained profile of important trial which is in long term follow-up prior to primary analysis.
Year(s) Of Engagement Activity 2014
URL http://meetinglibrary.asco.org/content/133202-144
 
Description ST02 MAGIC Gene expresssion profiling study ASCO 2013 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Shared information on translational research from a unique data set

none at present, paper in draft.
Year(s) Of Engagement Activity 2013
URL http://meetinglibrary.asco.org/content/111749-132
 
Description ST03 ASCO 2012 trials in progress 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact encouraged interest in a new trial design

accrual continued to increase
Year(s) Of Engagement Activity 2012
URL http://meetinglibrary.asco.org/content/99796-114
 
Description ST03 Trials on progress poster ASCO 2013 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Described further planned changes to the trial design, oppportunity for discussion with potential participants

Good accrual continued
Year(s) Of Engagement Activity 2013
URL http://meetinglibrary.asco.org/content/115231-132
 
Description ST03 launch meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Launch meeting to introduce the ST03 trial to staff at co-ordinating centres, provide context and opportunity for discussion/questions.
Year(s) Of Engagement Activity 2007
 
Description ST03 preliminary safety data ASCO 2010 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Reported results of a planned phase II safety assessment in the ST03 trial.
Year(s) Of Engagement Activity 2010
 
Description STO2/MAGIC Germ line polymorphisms ASCO 2014 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Shared translational data from a unique study

None as yet, paper in draft
Year(s) Of Engagement Activity 2014
URL http://meetinglibrary.asco.org/content/131490-144