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International clinical trials setting for rare cancers: organisational and regulatory constraints—the EORTC perspective

Author Interview

Emad Shash

Clinical Research Physician, EORTC, Brussels, Belgium and Medical Oncology Department, National Cancer Institute, Cairo University, Egypt

 

1) Can you tell me a bit about the EORTC? The EORTC is a pioneer in promoting multi-disciplinary cancer clinical research and pan-European collaboration and links a network of more than 2,500 clinicians and scientists in more than 300 hospitals in over 30 countries. It encompasses all aspects of cancer clinical research, from translational research and new drug development to large phase III clinical trials and meta-analyses.

EORTC Headquarters in Brussels handles some 30 protocols that are permanently open to patient entry, over 50,000 patients who are in follow-up, and a database of more than 180,000 patients.

The ultimate goal of the EORTC is to improve the standard of cancer treatment by developing new agents and innovative approaches and to test more effective treatment strategies using commercially available drugs, or surgery and radiotherapy.

EORTC studies have contributed to success stories in drugs development including the registration of several drugs by the United States Food and Drug Administration and the European Medicines Agency. The EORTC has a proven track record in establishing new standards, e.g. RECIST, QOL, etc., and in changing clinical practice. The EORTC Headquarters staff provide full clinical, scientific, operational, quality assurance, and regulatory support for clinical and translational research projects, and augments this support with strong expertise in biostatistics, clinical study design and methodology, endpoint definition and analysis, etc…


2) What did you work on before you joined EORTC? I graduated from the Kasr Al-Aini Medical School, Cairo University, and did my residency in Medical Oncology at the National Cancer Institute, Cairo University. Following my specialization in oncology, I was appointed as a faculty member (associate Lecturer at the Medical Oncology Department, NCI, Cairo University). Since my early residency, I have been very involved in cancer clinical research and have been an investigator in numerous national and international phase II and III clinical trials. This helped to gain a deep appreciation of the importance of research in the field of medicine to improve medical practice. Alongside my role as a physician, I have also contributed to the development of cancer awareness.


3) Tell us about your role at EORTC. As a Clinical Research Physician, I support the EORTC Gynecological Cancer and Radiation Oncology Groups. As part of my interests lie in the field of rare cancers, I am active in the development of clinical trials for Gyne-sarcoma entities as well as other transverse collaborative projects between the various EORTC disease oriented groups. As a point of explanation, the clinical research physician shares the responsibility for the scientific development and the execution of clinical trials conducted within EORTC network of institutions.    


4) How did you get involved in rare cancer clinical trials? I'm sharing in the development of clinical trials for Gyne-sarcoma entities; in one of these trials we are investigating the role of anti-VEGF therapy as maintenance in high grade uterine sarcoma; in which this sub-population have a very dismal survival and there is no standard of care due to rarity. In another trial, we will try to investigate the role of aromatase inhibitors in endometrial stromal sarcoma


5) Why can’t research for rare diseases be conducted in the same way as more common clinical entities? The prevalence of rare diseases may vary among diverse patient populations. An entity that is rare in one patient population may be common in another. For example, several malignancies are considered rare in the pediatric but not the adult population, because, in general, fewer children develop cancer as compared to adults.
Patients suffering from rare cancers often face challenges, including late or incorrect diagnoses, difficulties finding clinical expertise and accessing appropriate treatments, uncertainty in clinical decision making with difficult and rare access of these patients to clinical trials. Treatment choice is difficult when the patient is diagnosed with a rare disease or a pathological or molecular pattern and little information is available in the literature. In such situations, clinicians will base treatment decisions on retrospective data or case report series with a lower scientific level of evidence than that obtained from randomized controlled clinical trials.

 

6) What are the main problems in setting up clinical trials for rare cancers? The main challenge in performing appropriate clinical trials for rare cancers is the small number of patients affected and therefore available for clinical research. Observational retrospective series or single-arm clinical trials often represent the highest level of evidence available. Most single centers or national clinical trial consortiums cannot accrue the number of patients required for a robust randomized controlled trial in a reasonable amount of time.
In order to reduce the number of patients required, oncology trials are often designed using surrogate endpoints, such as tumor response rate or progression-free survival, as a pragmatic solution, even though these do not always correlate adequately with clinically meaningful endpoints, namely the duration and quality of patients’ life.
In this, international collaboration is essential, and the EORTC is the preeminent European organization conducting cancer clinical trials at the pan-European level. Currently we are running clinical trials within similar platform ideas such as the International Rare Cancer Initiative (IRCI) and cutaneous lymphoma task force platform,


7) What about funding for rare cancer trials? The relatively small number of patients available for randomized controlled trials can be addressed by building multi-center national or international networks of institutions. However, intergroup studies introduce additional challenges; since many parties are needed, and these must agree on a specific project to initiate and on how to work together to successfully complete the trials. In such a setting, operational difficulties, though not specific to rare cancer trials, are further amplified due to the scale of the projects.
We can identify specific problems common to most intergroup rare cancer trials. Cost can increase disproportionately to the number of enrolled patients and become a burden for trials that are already underfunded. Practical issues, such as ensuring reliable communication between sponsors, laboratories, and investigators; timely drug delivery at clinical sites; and adequate monitoring and follow-up can even represent a source of bias for the results of the clinical trial. By definition, most centers will only enroll a small number of patients, so maintaining adequate quality of care becomes very difficult.
Cooperation between various networks is further complicated when a multi-disciplinary approach is required. Phase III clinical trials may involve multiple treatment modalities (e.g. surgery or radiotherapy), central pathology or imaging review, integrated translational research, quality of life assessment, or quality assurance. In such cases, a lot of preparatory work is necessary among the involved networks in order to have a homogeneous approach to all of these aspects, yet the resources for such work are often unavailable.


8) How can people with rare cancers find out about the relevant clinical trials? Patients with cancer should first discuss treatment options with their physician. They may also contact the EORTC which has access to a network of expert oncologists: http://www.eortc.org/contact
The EORTC is now also very engaged in setting up molecular screening platforms, such as SPECTAcolor, which will increase opportunities for patients to access clinical trials with new molecularly defined approaches. In a way, cancer as a whole is becoming a collection of rare diseases, a disease that can be classified into molecular sub-entities. Improving treatments for patients with cancer will require screening platforms and international cooperation in order to accrue the necessary number of patients who bear the target of interest. The EORTC is very much active in defining the future of cancer therapy.

Read Emad Shash's article in full



Founding partners

European Cancer Organisation European Institute of Oncology

Founding Charities

Foundazione Umberto Veronesi Fondazione IEO Swiss Bridge

Published by

Cancer Intelligence