1. Who are the principal investigators?
Dr Martine Piccart is the TRANSBIG project coordinator and a co-principal investigator of the MINDACT trial. She is currently the Head of Medicine at the Jules Bordet Institute in Brussels, Belgium, and also the chair of the Breast International Group (BIG), which she created in 1996. Dr Piccart already has extensive experience in developing partnerships with experts throughout the world. The scientific director of TRANSBIG is Dr Fatima Cardoso, also based at the Jules Bordet Institute; Dr Cardoso also acts as co-principal investigator of the MINDACT trial. Dr Emiel Rutgers is a co-principal investigator of the MINDACT trial and is a breast surgeon at the Netherlands Cancer Institute (NKI) in Amsterdam. Dr. Laura Van ’t Veer is the chief scientist at the NKI involved in the MINDACT trial. The MINDACT trial will be sponsored and coordinated by the European Organisation for the Treatment and Research of Cancer (EORTC).
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2. How will the various partner institutions be involved in TRANSBIG?
Each of the partner institutions brings with it specific expertise, falling into different categories. For example, several of the TRANSBIG partners are specialised in microarray technology, and they have tumour resources essential to the validation phase of the MINDACT study. Others are top European institutions with regard to technologies and techniques that will be focussed on at a later stage in the project (e.g., proteomics, RT-PCR). Two partners will participate as experts in bioinformatics and biostatistics, without which the data generated from trials like MINDACT could not be properly analysed. A majority of the TRANSBIG partners are well known cancer research and treatment hospitals that have extensive experience with translational research as well. Many of these will be “national coordinating centres”, which means they will serve as the key contacts for the countries involved in MINDACT, including for the recruitment of patients. Still other partners are collaborative research groups that are also members of the BIG network and whose expertise lies in running – and contributing patients to — large, international, multi-centre trials. Finally, TRANSBIG includes partners that contribute their expertise as networks with extensive links to the wider scientific and patient communities. All these areas of specialisation are needed for TRANSBIG to succeed.
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3. Who should be contacted about requests for interviews and presentations?
The BIG/TRANSBIG secretariat (TRANSBIG@bordet.be and BIG@bordet.be) should be contacted about all specific requests for interviews and presentations. In this way there is a single contact point, and the Secretariat can designate the most appropriate person to respond to the request.
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4. What does TRANSBIG stand for?
TRANSBIG is an abbreviation for “Translating molecular knowledge into early breast cancer management: building on the BIG (Breast International Group) network for improved treatment tailoring.” TRANSBIG refers to a new research network involving 39 partners in 21 different countries in Europe that will be linked to an existing one, BIG. TRANSBIG has recently been created to accelerate the incorporation of new technologies into the breast cancer clinical practice. Translational research is a new type of research that provides the link between the discoveries in the laboratory (basic science research) and their application for the benefit of patients (clinical research). It functions as a bridge between these two worlds and is based on two principles often referred to as “bench to bedside” and “bedside to bench”.
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5. What does MINDACT stand for?
MINDACT stands for “Microarray in Node Negative Disease may Avoid ChemoTherapy”. MINDACT is the name of the clinical trial that will be using new microarray technology in the risk assessment of breast cancer patients. It is the first project to be run under the TRANSBIG umbrella.
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6. What is microarray technology?
Microarray technology is a new technique that allows scientists to identify a “genomic code” or “signature” of each individual cancer by displaying the genes it consists of. The advantage of this method is that it allows thousands of genes to be seen at once, rather than just one or two. This is very helpful to scientists, as there are many genes that contribute to the cancer behaviour- i.e. growth, death and reproduction of cancer cells- and at the moment their exact roles are unclear. This method allows us to compare genes between different tumours. In this way we may learn why some breast cancers behave differently from others in an unpredictable manner. Each tumour has its own unique genetic code or signature that may help us to predict if the cancer is likely to come back (prognostic value) or if the cancer is likely to respond to certain types of treatment, i.e. chemotherapy or hormonal therapy (predictive value)
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7. What is the aim of MINDACT?
The aim of MINDACT is to show that the simultaneous use of the genomic signature found by the Netherlands Cancer Institute using 70 genes together with the methods currently used at determining which women need further additional chemotherapy after their breast cancer has been surgically removed, and which women don’t, is better than the use of the current methods alone. If this hypothesis is correct, the overall quality of life for many women with breast cancer will be improved, and the health care costs associated with such cancer treatment can be reduced, as up to 20%
fewer women will require extra treatment after their breast cancer has been removed.
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8. Why is MINDACT so important?
Breast cancer is the most common cancer amongst women in developed countries, affecting 1 in 8 to 10 women in their lifetime. Nowadays breast cancer can be cured if diagnosed and treated at an early stage. Most women will receive additional treatment such as hormonal treatment or chemotherapy. At present the methods we use to determine if one woman’s breast cancer is more likely than another to come back are imperfect. As a result a lot of women are treated with chemotherapy, though they may actually not need it. This is because breast cancer is a disease that has many faces and behaves differently in different women. MINDACT will determine whether analysing a tumour’s gene signature adds important information to the current methods we already use in determining the way each breast cancer will behave. In this way chemotherapy can be given only to the women who need it, and many women can be spared unnecessary treatment.
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9. When has the clinical trial MINDACT started?
After an extensive preparation phase, that included the validation of the 70-gene signature in women treated in several European hospitals, the MINDACT trial was launched in January 2007 in Belgium followed a few months later by The Netherlands and France.
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10. How many participants will be enrolled in MINDACT?
About 6000 women are expected to participate worldwide, and the trial is expected to complete recruitment within 3 years. At the time of surgery to remove the tumour, a sample will be sent to the Netherlands for microarray analysis. A “bank” of these samples and other biological materials will be created for further important research. (See below for details).The women participating in MINDACT will be recruited primarily from Europe and Latin America, though potentially Canada and Australia may become involved.
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11. Why is MINDACT so different from other trials in breast cancer?
At the moment clinical trials help us work out whether new treatments for breast cancer are better than the old ones. However, even if it is found that a new treatment is on average better than another one, only some women will benefit significantly from it, and others may actually be helped only very little or not at all. This is because breast cancer is a disease that develops very differently in each woman. Inevitably, this inefficient way of treating patients reduces the quality of life for many women and places a considerable burden on healthcare systems as well as the economy.
MINDACT is so different from other trials in breast cancer because microarray technology will play a central role. Ultimately, it is hoped that the results of MINDACT will show that using the 70-gene signature together with the current methods will be a better way at predicting which breast cancers will come back. If this is the case, then we can be more accurate in deciding which women need additional treatment such as chemotherapy. Additionally, with further related research, we may soon be able to identify specific genetic codes or signatures that help us to define the best treatment options for each patient. In other words, we hope that through this trial and using this new technology, we will be able to begin tailoring treatment to the individual women, rather than treating all women the same way.
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12. What is the difference between BIG, TRANSBIG and MINDACT?
TRANSBIG is a research network dedicated to high-level collaboration that will contribute dramatically to advancing individualized treatment for breast cancer patients. Among its many strengths is the fact that it is linked to an already existing network of groups around the world that conduct large breast cancer clinical trials together – the Breast International Group (BIG). In this way, the connection is guaranteed between what scientists learn in the laboratory and what physicians and patients decide together about treatments in the clinic. MINDACT refers to the first clinical trial that will be conducted by TRANSBIG.
TRANSBIG will be built on the existing BIG network, by incorporating translational research components into existing BIG trials. Both networks are coordinated by the BIG/TRANSBIG Secretariat in Brussels.
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13. How will TRANSBIG be funded?
Recognising the potential impact of TRANSBIG in breast cancer research, the European Commission has awarded TRANSBIG partial funding under the 6th Framework Programme for Research. As such, all specific references to TRANSBIG must acknowledge this funding. Seven million Euro has been allocated to TRANSBIG, which is approximately one- fifth of the expected budget.
Critical additional funding is being secured through partnerships with the pharmaceutical industry and diagnostics companies. The pharmaceutical companies currently involved in the MINDACT Trial are Novartis, F. Hoffmann-La Roche and Sanofi-Aventis. The diagnostics company that is a partner in the TRANSBIG consortium is Agendia. To date the project has also received several grants from organizations such as the Breast Cancer Research Foundation, the Susan G Komen Foundation , the Fondation Contre le Cancer , the Jaqueline Seroussi Memorial Foundation and the Prix “Mois du Cancer du Sein”.
In view of the tremendous potential impact of TRANSBIG and MINDACT on future breast cancer management, funding from cancer societies, national governmental and other sources is also being sought.
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14. What is Agendia?
Agendia is a biotechnology SME (small/medium enterprise) that is a spin-off of the NKI (Netherlands Cancer Institute) where the 70-gene signature was developed. The commercial name of the 70 gene signature is Mammaprint®. Agendia is a small-and-medium sized enterprise (SME) member of the TRANSBIG consortium, as defined in the 6th European Framework programme. Agendia will be responsible for performing the genomic risk assessment with the 70 gene signature as well as whole genome complex arrays on all the patients enrolled in the MINDACT Trial. These gene expression evaluations will be done on the Agilent microarray platform. A contract outlining all the details of this cooperation is being concluded.
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15. Who will own the TRANSBIG Database?
The TRANSBIG Clinical Database will be in the hands of the EORTC and will be owned by the TRANSBIG Consortium Members (through BIG). Agendia will be blinded to clinical-pathological data. The TRANSBIG Microarray Database will also be owned by the TRANSBIG consortium.
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16. Where will the tumour blocks be kept?
Tumour blocks from the 6.000 women participating in the MINDACT clinical trial will be kept in the TRANSBIG biological materials bank. This facility will be set up especially for TRANSBIG by World Courier, an international company specialised in the shipment and storage of biological materials, in Brussels. Several TRANSBIG consortium partners are involved in setting up the biological materials bank, and the TRANSBIG Steering Committee will govern access to the samples. The advantage of archiving biological materials in a neutral site is that there will be no conflict of interest and anyone who has a research project approved by the TRANSBIG Steering Committee will have access to the samples. A detailed procedure for submission of research proposals and the review process is being developed.
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17. What is Adjuvant! Online
At the heart of this trial is the hypothesis that genomic risk assessment will outperform clinical-pathological risk assessment. Therefore, much attention has been devoted to defining the best possible clinical-pathological risk assessment as it is the control group. The TRANSBIG Steering Committee agreed to use Adjuvant! Online for the clinical-pathological risk assessment. Adjuvant! Online is a web-based decision tool developed by Dr. Peter Ravdin of the University of Texas in San Antonio. This model calculates the risk of relapse and death for each specific patient at ten years. This tool is user-friendly, widely available and popular with physicians around the world. Dr. Ravdin has been working actively with TRANSBIG and is a member of the TRANSBIG Steering committee. For more information please refer to:
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18. Will there be an opportunity to conduct Microarray research in the Affymetrix platform?
Yes. Proposals may be to use Agilent or Affymetrix, or other translational research platforms. Provided that a proposal receives prior approval by the TRANSBIG Steering Committee, any variety of translational research projects can be conducted with the MINDACT tumour samples.
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19. How are patients and physicians going to cope with four Patients Informed Consent Forms (ICFs) and the complexity of MINDACT?
The MINDACT clinical trial is difficult to explain to patients. Because of this the four ICFs have been written with great care – and reviewed by patient groups – to best inform patients. We have also produced a DVD with a London based company called Windfall Digital. The aims of the DVD are to explain the trial to eligible women after they have had surgery to remove the tumour and to help them decide to participate or not in this complex trial. The DVD is to be used in consultation with a physician or research nurse, and guides women through the different parts of the MINDACT trial, explaining the three randomizations and devoting extended time to the first randomization. This is the most complex randomization when risk is assessed with the classical clinical-pathological criteria versus the genomic risk done with the 70 gene signature Mammaprint®.
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20. Will there be a MINDACT Steering Committee and an Independent Data Monitoring Committee (IDMC)?
Both these committees will exist. The MINDACT Steering Committee will be formed before the trial starts recruiting and will include representatives from groups participating in the trial and other individuals that are not currently members of the TRANSBIG Steering Committee. The IDMC will also be formed in 2006, once patients start being enrolled in MINDACT.
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