This seminar will mainly focus on critical points related to clinical trials.
Among the others, a critical point is related to the clinical trial endpoints, other than survival, that objectively demonstrate meaningful clinical benefit. In fact, with the introduction of molecular pathology, patients and their oncologists now deal with a greater variety of malignant diseases than ever before, each of which likely benefits from a unique approach to treatment. Furthermore, many new drugs determine slow tumor progression instead of causing tumor shrinkage. Therefore cancer drug trials may require more patients and the more frequent use of placebo controls, thus presenting greater recruitment challenges as well as requiring a long period of time to reach major clinical endpoints, more expensive clinical documentation to record progression events, and additional regulatory scrutiny.

For all the mentioned reasons potential surrogate endpoints and other biomarkers have been identified and evaluated and they will be discussed during the seminar.

Another critical point is related to the clinical trial conduction within the sites. Therefore it is also important to know what deviations, violations and exceptions represent and when they could have an impact on the clinical trial results. On the other hand, it is important to underline in which situations a waiver could be given and a less strict Company’s behavior could facilitate the study without compromising the study results.

Why should you attend?

More than 80% of drugs for all indications entering clinical development do not get marketing approval, with many failing late in development often in Phase III trials, because of unexpected safety issues or difficulty determining efficacy, including confounded outcomes. Many factors may be involved in this low success rate: among the others, the limited knowledge of the determinants of drug sensitivity and resistance; heterogeneous patient populations and lack of biomarkers to identify patients most likely to benefit from specific treatments; the design of the clinical trials, which are often made on the basis of the “traditional statistical” requirements; the lack of agreement among clinicians, investigators, and regulators as to what constitutes clinical benefit in some circumstances.

Furthermore, several agents that obtain the approval are criticized by Medical Oncologists. In fact, regardless of approval, phase III trials with new drugs may presents some criticism that could lead on one hand to delay or limitation in the approval and on the other hand on a limited belief in the drug within Medical Oncologists. This may cause a reduced prescription of the drug, despite its real activity and efficacy.

Areas Covered in the Session:

• Traditional statistical design of clinical trials in Oncology (phases of studies, standard endpoints…)
• Introduction of targeted therapies in the Oncology field and of the related different needs (i.e. identification and validation of biomarkers). Examples will be provided about the most important types of tumors (lung cancer, colorectal cancer, breast cancer), as well as the more rare diseases.
• Analysis of the new endpoints related to the different mechanism of action of the new therapies will be provided.
• Requirements of the regulatory authorities, with a special focus on the rebounds in the European and Italian System (with examples of major criticisms of some relevant trials)
• Meaning of the terms deviation, violation and exception and their impact on the clinical trials conduction and results.
• Phase III statistical design of clinical trials in Oncology, in particular with new drugs (analysis of recent examples of phase III trials which present limitations).