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The Synergism or Long Duration (SOLD) Study A randomised phase III study comparing trastuzumab plus docetaxel (HT) followed by 5-FU, epirubicin, and cyclophosphamide.

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Presentation on theme: "The Synergism or Long Duration (SOLD) Study A randomised phase III study comparing trastuzumab plus docetaxel (HT) followed by 5-FU, epirubicin, and cyclophosphamide."— Presentation transcript:

1 The Synergism or Long Duration (SOLD) Study A randomised phase III study comparing trastuzumab plus docetaxel (HT) followed by 5-FU, epirubicin, and cyclophosphamide (FEC) to the same regimen followed by single-agent trastuzumab as adjuvant treatments for early breast cancer

2 UK Chief Investigator Dr Judith Fraser Beatson West of Scotland Cancer Centre 1053 Great Western Road Glasgow G12 0YN Tel:

3 Study Chief Investigator Professor Heikki Joensuu Clinical Research Institute Helsinki University Central Hospital Ltd PL 700 (Haartmaninkatu 8/Biomedicum Helsinki) FIN HUS Finland

4 Study Sponsor The Finnish Breast Cancer Group Clinical Research Institute Helsinki University Central Hospital Ltd PL 700 (Haartmaninkatu 8/Biomedicum Helsinki) FIN HUS Finland

5 UK Sponsors Representative Greater Glasgow and Clyde NHS Board

6 UK Study Team - Glasgow Project Manager Liz-Anne Lewsley, Clinical Trial Co-ordinator Diann Taggart, Study Monitor Jan Graham,

7 SOLD Population Female patients with HER2+ breast cancer with no overt distant metastases, and who are considered to have a high risk of breast cancer recurrence

8 In both Arms:  RT (according to the institutional practise)  Endocrine therapy for a minimum of 5 yrs when ER/PgR +ve SOLD Design FE 75 C 3-weekly trastuzumab (H) RANDOMIZERANDOMIZE Docetaxel 80/100 mg/m 2 H to complete 1 year (14 3-wkly infusions) H for 9 wks

9 Treatment Regimens Arm A HT x 3 → FEC75 x 3 –Herceptin (H) administered either weekly or 3-weekly –Either the weekly or the 3-weekly schedule should be used consistently throughout the study –Weekly: First dose 4 mg/kg, subsequent doses 2 mg/kg –3-weekly: First dose 8 mg/kg, subsequent doses 6 mg/kg –Herceptin infused prior to docetaxel (T). If T administration needs to be deferred, H administration will also be deferred –Docetaxel doses must be consistent, either 100mg/m² or 80mg/m² in all patients, adjustments can only be made for age –G-CSF and dose reductions allowed

10 Arm B HT x 3 → FEC75 x 3 → H (3 wkly) x 14 –Chemotherapy as in Arm A –Single-agent H after chemo: 3-weekly - first dose 8 mg/kg, subsequent doses 6 mg/kg

11 SOLD Objectives Primary –DFS Secondary: –Overall survival (OS) –Distant disease-free survival (DDFS) –Cardiac disease-free survival (CDFS) –LVEFs –Safety and toxicity –QoL (EuroQol EQ-5D) –Collection of biological samples (tumour, serum)

12 Key Inclusion Criteria HER2+ invasive BC –Assessed with CISH or FISH –If not available IHC+++ A high risk of recurrence with either –N0 with the longest invasive tumour diameter >5mm and histology grade >2 >10mm histological grade irrelevant –Histologically confirmed node+ disease Please refer to protocol for full list of inclusion criteria

13 Key Exclusion Criteria Presence of distant metastases Inflammatory breast cancer Clinically significant cardiac disease LVEF <50% (either ultrasound or MUGA) Neoadjuvant chemotherapy WHO performance status >1 >12 weeks between breast surgery and randomisation Prior malignancy within the past 5 years, except basal cell carcinoma or carcinoma in situ of the uterine cervix Pre-existing motor or sensory neurotoxicity of > grade 2, unless related to mechanical etiology Please refer to the protocol for a full list of exclusion criteria

14 Randomisation Randomisation for the study is web based https://www.ctru.auckland.ac.nz/sold/ If website down for any reason, randomisation performed via fax: Patients are stratified on the following variables –no. of +ve nodes –HER2 assessment method –Centre –ER positivity

15 Study Website https://www.ctru.auckland.ac.nz/sold/ Username and password required Once site receives all necessary approvals application for username and password will be issued Key study documents can be found and downloaded from the website – CRFs, SOPs, QoLs, SAE forms, CIOMS forms etc Recruitment reports can be generated on the site allowing tracking of accrual Do Not use the patient information sheet from the website as we have our own ethics approved UK version

16 RT and Endocrine Therapy Radiotherapy –should be administered according to local practice (mandatory following breast conserving surgery) –Recommended to be started within 2 months of completion of chemotherapy Hormonal therapy –When cancer ER and/or PR positive –Choice of therapy at clinicians discretion –Administered for a minimum duration of 5 yrs –Recommended to be started within 3 months of completion of chemotherapy

17 SOLD Patient Numbers Planned sample size: 3,000 worldwide from the UK 1 st patient recruited into study January patients recruited to end of July 2013, 282 recruited UK (8 England, 274 Scotland) from March 2009 Recruitment expected to last until end of 2015

18 SOLD Recruiting Countries –Belgium –Brazil –Finland –Germany –Iceland –Italy –Korea –Netherlands –Serbia –Sweden –New Zealand –United Kingdom

19 Safety SAEs/SUSARs graded according to CTCAE v 3.0 SAEs/SUSARs also evaluated during the single-agent trastuzumab phase in both arms SAEs/SUSARs should be reported by fax to the SOLD Study in Helsinki, Finland

20 Safety SOLD Study Centre are responsible for deciding on SUSAR status and providing SUSAR reports Dr Fraser, as CI for UK, is then responsible for reporting SUSARs to MHRA, Main REC, and participating sites in the UK Dr Fraser is also responsible for submitting the Development Safety Update Reports (DSURs), (prepared by the Finnish Breast Group), to MHRA, Main REC, and participating sites in the UK

21 Patient Safety Evaluations LVEF monitoring with either echo or MUGA –Baseline method should be consistent throughout per patient –measured 6 times (baseline, weeks 18, 31, 43, 61, and at 3 years)

22 Research Blood Samples 2ml serum and 2ml plasma (baseline, week 61, then annually) Collection optional for patient Should be stored at least -20 Only study specific labels will be supplied by the Sponsor, all tubes from stock

23 Transportation of Serum and Plasma Samples Samples should be shipped on dry ice directly to the Study Centre in Finland Professor Heikki Joensuu Department of Oncology Helsinki University Central Hospital Haartmaninkatu 4 P.O.Box 180 FIN Helsinki, Finland An should be sent to Mia Viskari with a copy to Prof Joensuu advising that samples have been shipped. Please see shipping and handling instructions in the Investigator Site File for courier details

24 Tumour Samples Paraffin embeded tissue block –gene amplifications, mutations, signalling proteins Again, collection optional for patient Will be used for quality control of HER2 assessment Samples should be sent via mail to Study Centre in Helsinki, Finland (as previous). Please see shipping and handling instructions in the Investigator Site for further details

25 Pharmacy All drugs to be taken from pharmacy stock, no special supply arrangements A pharmacy file will be provided with accountability logs etc An IMP Management Document will be supplied

26 Doses and Administration Docetaxel, 5-FU, Epirubicin and Cyclophosphamide doses are calculated per BSA Herceptin dose calculated /kg Dose adjustments for weight only to be made where there is a difference of 10% to that of the baseline weight Protocol states that FEC administration should be IV, have confirmation from CI that bolus is acceptable should this be normal practice.

27 Dose Banding If dose banded products are used as IMPs: –The dose banded product must be routinely used within the Trust/Board for the treatment of patients receiving standard therapy, i.e., outwith a clinical trial –The dose banded product must not be purchased or obtained by pharmacy specifically for use within the study. Instead, it must be procured as part of routine pharmacy stock –Dose banded products to be used in the study must be labelled as per section study procedures only in response to an individual patient prescription –There must be formal agreements in place between the Board/Trust and the supplier to ensure the product is of an appropriate quality; this may include local or national purchasing contracts –The supplier of the dose banded chemotherapy must maintain an adequate audit trail that would permit the batch number of the original product and diluent to be traced should this be required –The batch number, manufacturer and supplier of any dose banded drugs must be recorded by pharmacy for every dose used within the clinical trial

28 Monitoring The study will be monitored by the CR-UK CTU in Glasgow. Each site will be visited at least once during study participation, again prior to interim analysis and again prior to final analysis. 100% of patients will have consent monitored. A minimum of 50% of patients will be monitored for a selection of key fields. It is important that case notes have as much information as possible contained within them to enable Source Data Verification Monitor will not remove CRF pages, these should be sent directly to Study Centre in Finland.

29 Thank You Thank you for your time, if you have any questions please detail these on your Investigator Initiation Presentation Acknowledgement when it is returned, or contact one of the following: UK CI - Dr Judith Fraser CTC – Diann Taggart PM – Liz-Anne Lewsley


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