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.
Organisations
- MRC Clinical Trials Unit (Lead Research Organisation)
- University of Leeds, United Kingdom (Collaboration)
- Imperial Cancer Research Fund (Collaboration)
- Cambridge University Hospitals NHS Foundation Trust, Cambridge (Collaboration)
- Genetech, Inc (Collaboration)
- Gustave-Roussy Institute (Collaboration)
- National Cancer Research Institute (Collaboration)
- National University of Singapore, Singapore (Collaboration)
- Imperial College London, United Kingdom (Collaboration)
- Poole Hospital NHS Foundation Trust, Pool (Collaboration)
- F. Hoffmann-La Roche AG (Collaboration)
- Royal Marsden NHS Foundation Trust (Collaboration)
Publications

Alderson D
(2017)
Neoadjuvant chemotherapy in oesophageal adenocarcinoma - Authors' reply
in The Lancet Oncology


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

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



Okines AF
(2013)
Bevacizumab with peri-operative epirubicin, cisplatin and capecitabine (ECX) in localised gastro-oesophageal adenocarcinoma: a safety report.
in Annals of oncology : official journal of the European Society for Medical Oncology

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

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

Smyth E
(2017)
Pharmacogenetic Analysis of the UK MRC (Medical Research Council) MAGIC Trial: Association of Polymorphisms with Toxicity and Survival in Patients Treated with Perioperative Epirubicin, Cisplatin, and 5-fluorouracil (ECF) Chemotherapy.
in Clinical cancer research : an official journal of the American Association for Cancer Research
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 | 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 | 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 |