New Strategies for Research

May 2, 2008

Applied Clinical Trials Supplements

Supplements-05-02-2008, Volume 0, Issue 0

How one group is transforming clinical cancer research across all of Europe.

The European Organization for Research and Treatment of Cancer (EORTC) has adopted a proactive pan-European strategy to develop, conduct, coordinate, and stimulate high-quality, science-driven translational and clinical cancer research, building on the rapidly evolving discoveries of clinicogenomic research.1 Implementation of the European Union Clinical Trials Directive 2001/20/EC, originally intended to protect the rights and well-being of human subjects and facilitate the regulatory procedures for the conduct of European clinical trials,2 continues to pose a major challenge for all those willing to initiate investigator-driven clinical trials.

Colette Lukan, MD

Additional hurdles to conducting clinically relevant cancer trials include the increasing costs of both translational and clinical research as well as the ever growing trend toward globalization of cancer research. New strategies are clearly required. As a leader in clinical cancer research over the past 45 years, the EORTC continues to devote its multidisciplinary expertise and research infrastructure platforms to further improve the standards of cancer care, advance the scientific understanding of the disease, and address pivotal strategic therapeutic questions.

Dr. Rémy von Frenckell, director of methodology and operations; Dr. Françoise Meunier, director-general; and Dr. Denis Lacombe, scientific director (left to right).

Up for the challenge

The EORTC is well positioned to forge new directions in clinical cancer research. EORTC clinical trials carried out within the EU, other European countries, and across the world accrued more than 20,000 patients in the period spanning 2003 to 2007. This total includes just over 5000 patients recruited alone in the year 2007. Annual follow-up continues on a further 30,000 patients from past EORTC trials and the EORTC clinical database, housed at the group's headquarters in Brussels, now contains treatment outcome data for over 160,000 cancer patients. Fifty-six clinical trials are currently ongoing at the EORTC and actively enrolling patients.

In recent years, multiple novel agents have been discovered due to the remarkable developments in the understanding of the molecular basis of cancer. Further breakthroughs in the prevention, diagnosis, and treatment of cancer will be achieved primarily through translational research projects, efficient drug development, and the conduct of translational research-driven, large prospective randomized multicenter clinical trials. These require a global cooperative partnership approach coupled with new models of collaboration and funding to guarantee independent evaluation of new standards of care. Further significant improvements in the survival of cancer patients will depend on the ability of researchers to discover new drugs and novel treatment strategies tailored to the individual patient and to specific disease characteristics.

To meet the challenges of clinical cancer research in today's molecular era, the EORTC established the Network of Core Institutions (NOCI) to promote, support, and conduct high-quality translational research-rich trials across the EORTC disease-oriented groups. This strategy optimizes the transfer of basic molecular research discoveries to the development of targeted tailored cancer therapies in terms of time and quality by capitalizing on the broad research expertise and infrastructure of large institutions located in various European countries. Innovative translational research concepts are prioritized and evaluated in early Phase multitumor line trials. Further development is based on early trial outcome results, prospectively streamlined for validation in disease specific pivotal large Phase III confirmative EORTC trials. This represents a new project-focused research strategy that is time, resource, and financially efficient while at the same time provides a collaborative opportunity for both public and private sector research partnerships.

NOCI trials involve innovative complex study designs, elaborate translational research, and allow for the large-scale collection of blood and tissue samples or biospecimens in a prospective manner. A centralized independent EORTC tumor biobank facility will provide for the storage and management of a representative selection of these biospecimens with electronic linkage to a treatment outcome database. The NOCI initiative represents an unmatched potential not only for the advancement of cancer research but also for investigators, patients, and governments faced with the financial challenges of providing all citizens with the best standards of care. The NOCI strategy also addresses and guarantees the future of independent academic clinicogenomic cancer research in Europe.

Forging ahead

The EORTC developed a classification system that defines three broad categories of trials and utilizes this categorization to determine the place of each new trial proposal within its overall scientific strategy. High priority trials include randomized Phase III studies designed to answer a question that directly contributes to defining new standards of care or those with a strong "targeted" translational research component that may permit a fundamental advancement in the understanding of a particular cancer. A second application of this approach allows for the prioritization of resource and/or funding allocation.

This categorization facilitates the selection and prospective development of early phase multitumor clinicogenomic studies as well as "niche" specific and multimodality trials, thereby increasing the success of discovering and developing new standards of care. The EORTC will stimulate this scientific strategy by awarding several grants in 2008 for academic and clinicogenomic trial research proposals with the highest promise of defining new standards of cancer care.

In addition, the EORTC is actively seeking new ways to collaborate with national cancer research groups within Europe to address specific strategic research questions involving multimodality cancer treatments, such as surgery and radiotherapy and to guarantee the study of the less common types of cancer. These goals are achievable through highly specialized large Phase III trials conducted in niche areas of disease-specific expertise and the pooling of patient accrual at a pan-European level. This approach also permits the best use of locally developed technical, scientific, and research expertise in nationally run clinical trials.

This strategic approach to future EORTC clinical cancer research has a multilevel built-in mechanism to ensure and oversee the independence of EORTC research. This mechanism consists of several committees made up of experts that review and advise on all prospective EORTC clinical and translational research proposals and include the New Drug Advisory, Translational Research Advisory, Protocol Review, Scientific Audit, Quality Assurance, Independent Data Monitoring, Membership, and EORTC Headquarters Institutional Review Board Committees.

The EORTC headquarters, based in Brussels, is a central facility staffed by more than 150 members representing 14 different nationalities and provides all necessary support and management of EORTC clinical trials to a unique network of investigators located in 300 hospitals throughout Europe.

The EORTC has taken significant steps toward building upon successful past research initiatives; to setting standards for high-quality, scientifically sound, and clinically relevant cancer research; to working toward broader pan-European collaborations; and to establishing solid foundations for cancer research that will extend well into the 21st century.

Colette Lukan, MD is a consulting medical communication manager for the EORTC and a radiation oncologist with 20 years experience in the field of clinical trials. She can be reached at: colette.lukan@eortc.be

References

1. European Organisation for Research and Treatment of Cancer Current Research and Strategies Report 2008-2009, available at: www.eortc.be.

2. Directive 2001/20/EC of the European Parliament and of the Council, available at: www.eortc.be/Services/Doc/clinical-EU-directive-04-April-01.pdf.