1 MRC SUPREMO (BIG 2-04) Selective Use of Postoperative Radiotherapy aftEr MastectOmy Phase III randomised trial of chest wall RT in intermediate- risk breast cancer Kunkler I, Canney P, Price A, Anderson N, Dixon J, Sainsbury R, Aird E, Thomas G,Bowman A, Thomas J, Bartlett J, Devine I, Denvir M, McDonagh T, Russell N, Cairns J, Boon Chua, Karlsson P, Northridge D, van Tienhoven G, Velikova G,Walker A, Macdonald E

2 Protocol V29 Eligibility Guide – Non Neo-adjuvant & Neo-adjuvant Informed Consent Procedures SAE Guidelines Supremo Team Recruitment Agenda

3 Implemented on the 14 th February out of 157 sites confirmed approval for V29  UK: 104 out of 117  International: 4 out of 9 (5 China sites will continue to work to V27)  EORTC: 0 out of 31. New protocol approved in April 2011 and is due to be implemented by Summer Protocol V29

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6 Patients should have a verbal explanation of the trial and be given most recent MREC-approved Patient Information Sheet (PIS) for the main SUPREMO trial/TRANS-SUPREMO and Quality of Life/Health Economics sub-studies (version 29) Patient Consent Procedures 1 Patient Information

7 Consent forms must be printed on hospital headed paper & accompanied by centre’s standard radiotherapy information sheets All participating patients must sign the most recent version of consent forms (separate consent forms for Main trial/TRANS- SUPREMO, Quality of Life/Health Economics substudies). Patients must initial, not tick boxes PI to countersign forms, but PI can delegate responsibility as appropriate (must be clearly documented in delegation log). No trial procedures can be performed prior to the patient giving informed consent. Patient Consent Procedures 2 Consent Form Completion

8 4 copies of signed consent forms required Original copy should be kept in site folder Copy given to patient Copy sent to ISD CCTT Copy kept in patient hospital notes Patient Consent Procedures 3 Consent Form Copies

9 A SAE is defined as an untoward occurrence that: Results in death Is life threatening Requires hospitalisation or prolongation of existing hospitalisation Results in persistent disability or incapacity Is a congenital anomaly/birth defect Is otherwise considered medically significant by the investigator Serious Adverse Events 1 SAE Definition

10 For SUPREMO patients receiving radiotherapy the potential expected adverse events/reactions include: Skin reactions leading to chest wall tenderness and itching Chest wall pain Pneumonitis (inflammation of the lung) causing shortness of breath Osteitis (inflammation of the ribs) causing the ribs to fracture Late cardiac damage If any of the above expected reactions fall under the definition of SAE they should be listed on SAE/SUSARs form Serious Adverse Events 2 Expected Radiotherapy SAEs

11 Serious Adverse Events 3 Chemotherapy SAEs Chemotherapy related SAEs that require reporting Chemotherapy related SAEs that do not require reporting on SAE/ SUSAR form (unless they impact on delivery of the randomised treatment) 1.Wound infections 2.Necrosis of the mastectomy skin flaps 3.Any cardiac event 4.Development of any other serious medical condition between date of consent and planned start of radiotherapy (or equivalent period for those patients randomised to not receive radiotherapy) Hospitalisation due to: 1.Neutropenia 2.Febrile neutropenia 3.Diarrhoea 4.Infections, including those to Hickman line, catheter. 5.Pyrexia 6.Sore throat 7.Nausea or vomiting 8.Cellulitis

12 At the centre: Use SAE/SUSAR form to report all SAEs (even if the SAE is chemotherapy related) Fax copy to ISD Trials Unit within 24 hours (from site staff becoming aware) Do not delay because of missing information and/or signatures Local PI to assess whether unexpected, severity and/or related to radiotherapy Provide missing information (and outcome information) as soon as it is known Serious Adverse Events 4 Reporting

13 ISD Trials Unit will: Allocate an SAE number Forward initial report to CI immediately if local PI assesses event as unexpected Advise the PI if SAE is evaluated as a SUSAR Comply with NRES guidelines on reporting of SAEs Report all SAEs to DMEC/MREC on an annual basis Serious Adverse Events 5 Processing

14 SUPREMO Team Eve Macdonald Senior Trial Coordinator Julian Lipscombe Trial Coordinator Leigh Fell Trial Coordinator Ann Moncrieff Data ISD Cancer Clinical Trials Team Edinburgh

15 Randomisation service Advice on protocol and eligibility Investigator Site Files (ISFs) Regular newsflashes & website reports ( 10% Source data monitoring Trial Co-ordination Provided by ISD Trials Unit

16 Recruitment to date (as of 30/5/11) Main trial 1078 TRANS SUPREMO850 Quality of Life611 Cardiac substudy53 Health Economics41

17 Recruitment to date (cont.)

18 Thank you for your time. Questions?

19 ISD CANCER CLINICAL TRIALS TEAM