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The MRC SUPREMO clinical trial is a phase III multicentre international randomised trial assessing the role of adjuvant chest wall irradiation in ‘intermediate risk’ operable breast cancer following mastectomy and axillary clearance. It will provide a unique opportunity to expand our knowledge of the molecular mechanisms underlying the relapse of breast cancer and resistance to radiation therapy. Therefore the TRANS-SUPREMO sub-study has been established-
- to assess biomarkers in the tumours excised from patients in the SUPREMO Trial with the objective of determining if patients benefit differently according to biomarker status;
- to identify any differences in the phenotypes of tumours at local relapse according to treatment;
- to assess DNA, serum or plasma markers of cardiac risk, relapse risk or outcome within the SUPREMO trial.
For full background and methodology for the study please see the TRANS-SUPREMO section of the protocol.
Tumour tissue from patients who have consented to take part in the TRANS-SUPREMO study will include:
- Tumours excised prior to entry to the TRANS-SUPREMO study for all patients randomised
- Sera, plasma and whole blood collected prior to randomisation and at specified intervals during patient follow up.
All the tissue is archival tissue, collected routinely in the local pathology department of the hospital where the patient is treated. Blocks are loaned to the study for the taking of 20 slides and for the removal of cores used in the micro-arrays. The TRANS-SUPREMO Pathology Sub-committee will work with investigators, pathologists and associated staff to try to obtain tissue from every eligible TRANS-SUPREMO patient.
Sera, plasma and whole blood, are collected at intervals during the trial and also at time of relapse. These are collected routinely and are separated and frozen as soon as possible after collection. Samples are shipped for storage to the Endocrine Cancer Group in Edinburgh. Samples will be anonymised and identified by a unique trial number, pathology number (tumour samples), date of collection (blood/serum/plasma), patient date of birth and patient initials. Follow-up information will be linked through the unique trial number within the main clinical trial database. If a patient withdraws from the trial, she will be asked whether or not she wishes stored samples to be retained or destroyed.
For detailed information on sample handling procedures and storage and shipping of specimens, please see the TRANS-SUPREMO laboratory manual.
The MRC trial grant includes funding for the provision of blood sample kits for all UK trial patients, dry ice for transport of frozen samples to the central laboratory in Edinburgh and the collection of blocks for TRANS-SUPREMO from UK participating centres..
It is hoped that participating centres from other countries will be able to submit samples for all their patients entered into the Supremo trial. Dr Bartlett can be contacted to discuss in further detail, logistics and funding issues for international collaborators' participation in TRANS-SUPREMO.
The study is managed by the TRANS-SUPREMO Pathology Sub-committee whose Chairman, Dr John Bartlett, is appointed by TRANS-SUPREMO Steering Committee (SC) on which he also has a seat. Custodianship of the samples will be vested in the MRC TRANS SUPREMO SC on whose behalf Dr Bartlett will act as the de facto custodian. The TRANS-SUPREMO Pathology Sub-committee comprises:
1. Clinicians/pathologists/scientists appointed by the TRANS-SUPREMO SC or others by special appointment by the TRANS-SUPREMO SC, including: Prof. Ian Kunkler, Prof. Allan Price, Dr. Geraldine Thomas, Dr. James MacKay and Dr. Jeremy Thomas.
2. The TRANS-SUPREMO independent statistician, who will not be required to attend all meetings but will be available for consultations as necessary.
3 Mrs Anne Douglas, representing the ISD Cancer Clinical Trials Unit.
4. Independent reviewers, including Professor Ian Ellis from Nottingham and others co-opted as necessary.
The role of the Sub-committee is:
- To provide overall guidance and supervision of pathological or translational studies conducted in relation to the TRANS-SUPREMO Trial.
- To develop, and modify as necessary, the laboratory manual (ECG/07/TA01) for the collection of tissues/fluids within TRANS-SUPREMO (the Tissue Resource) for translational study.
- To develop further proposals for translational studies (irrespective of the need to use the Tissue Resource) and to find the means of funding such proposals as approved by the TRANS-SUPREMO Steering Committee.
- To receive from other parties, proposals for translational studies in connection with TRANS-SUPREMO, irrespective of their requirement to access the Tissue Resource, and to make recommendations to TRANS-SUPREMO Steering Committee on their acceptability/priority.
- To develop and modify as necessary guidelines for the care of the Tissue Resource collected from TRANS-SUPREMO.
- To provide oversight and management of the Tissue Resource and databank.
The TRANS-SUPREMO Pathology Sub-committee (PS) is responsible to the TRANS-SUPREMO Steering Committee (SC) . A core working group will be appointed by the PS to conduct necessary business on an on-going basis. This working party will meet as necessary. The full sub-committee will meet at least once every 12 months.
All proposals for the use of the tissue resource must obtain appropriate ethical approval.
The Intellectual property policy is contained in the Material Transfer Agreement.
The Recipient will inform TRANS-SUPREMO Secretariat (who will forward to TRANS-SUPREMO) forty five (45) days in advance of any oral presentation or publication referring to research involving the use of the Tissue to allow TRANS-SUPREMO the opportunity, if it so wishes, to file relevant patent applications for their protection. In all oral presentations or written publications referring to research involving use of the Tissue the Recipient will acknowledge TRANS-SUPREMO and TRANS-SUPREMO’s provision of the Tissue unless otherwise requested by TRANS-SUPREMO. This acknowledgement will normally reflect the intellectual input of TRANS-SUPREMO and TRANS-SUPREMO members by inclusion in the publications' authorship.
All data arising from the use of this material will be provided to the TRANS-SUPREMO for inclusion in the TRANS-SUPREMO database. The applicant will be responsible for ensuring reasonable costs relating to this transfer will be underwritten. Such data will, at the discretion of the TRANS-SUPREMO steering committee, be provided for future analysis where such analysis may enhance future research proposals.
Useful Links ECG website,
TRANS-SUPREMO and cardiac sub-study laboratory manual
TRANS-SUPREMO laboratory manual
MRC Supremo protocol
For further information on TRANS-SUPREMO please contact:
Dr John Bartlett at transsupremo@ed.ac.uk
Kirsten Murray
ISD Cancer Clinical Trials Team
Gyle Square
1 South Gyle Crescent
Edinburgh EH12 9EB
Telephone: +44 (0) 131 275 6630
E-mail: kirsten.murray@isd.csa.scot.nhs.uk
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