Transcript SOLD Investigator Meeting

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
UK Chief Investigator
Dr Judith Fraser
Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow G12 0YN
[email protected]
Tel: 0141 301 7104
Study Chief Investigator
Professor Heikki Joensuu
Clinical Research Institute Helsinki
University Central Hospital Ltd
PL 700
(Haartmaninkatu 8/Biomedicum Helsinki)
FIN-00029 HUS
Finland
Study Sponsor
The Finnish Breast Cancer Group
Clinical Research Institute Helsinki
University Central Hospital Ltd
PL 700
(Haartmaninkatu 8/Biomedicum Helsinki)
FIN-00029 HUS
Finland
UK Sponsors Representative
Greater Glasgow and Clyde
NHS Board
UK Study Team - Glasgow
Project Manager
Liz-Anne Lewsley, 0141 301 7193
[email protected]
Clinical Trial Co-ordinator
Diann Taggart, 0141 301 7234
[email protected]
Study Monitor
Jan Graham, 0141 301 7956
[email protected]
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
SOLD Design
R
A
N
D
O
M
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Z
E
Docetaxel
80/100
mg/m2
FE75C
3-weekly
trastuzumab (H)
In both Arms:
RT (according to the
institutional practise)
H for 9 wks
H for 9 wks
Endocrine therapy for
a minimum of 5 yrs
when ER/PgR +ve
H to complete 1 year
(14 3-wkly infusions)
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
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
SOLD Objectives
• Primary
– DFS
• Secondary:
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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)
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
Key Exclusion Criteria
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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
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: +358 9 471 73 181
• Patients are stratified on the following variables
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no. of +ve nodes
HER2 assessment method
Centre
ER positivity
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
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
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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
SOLD Patient Numbers
• Planned sample size: 3,000 worldwide
• 300-500 from the UK
• 1st patient recruited into study January
2008
• 1809 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
SOLD Recruiting Countries
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Belgium
Brazil
Finland
Germany
Iceland
Italy
Korea
Netherlands
Serbia
Sweden
New Zealand
United Kingdom
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
+ 358 9 471 73 181
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
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)
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
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-00029 Helsinki, Finland
• An email should be sent to Mia Viskari ([email protected]) with a
copy to Prof Joensuu ([email protected]) advising that samples
have been shipped. Please see shipping and handling instructions
in the Investigator Site File for courier details etc.
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
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
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.
Dose Banding
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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
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.
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
[email protected] 0141 301 7104
• CTC – Diann Taggart
[email protected] 0141 301 7234
• PM – Liz-Anne Lewsley
[email protected]
0141 301 7193