Abstract
Randomized clinical trials are considered the milestones of clinical research in oncology, and guided the development and approval of new compounds so far. In the last few years, however, molecular and genomic profiling led to a change of paradigm in therapeutic algorithms of many cancer types, with the spread of different biomarker-driven therapies (or targeted therapies). This scenario of “personalized medicine” revolutionized therapeutic strategies and the methodology of the supporting clinical research. New clinical trial designs are emerging to answer to the unmet clinical needs related to the development of these targeted therapies, overcoming the “classical” structure of randomized studies. Innovative trial designs able to evaluate more than one treatment in the same group of patients or many groups of patients with the same treatment (or both) are emerging as a possible future standard in clinical trial methodology. These are identified as “master protocols”, and include umbrella, basket and platform trials. In this review, we described the main characteristics of these new trial designs, focusing on the opportunities and limitations of their use in the era of personalized medicine.
Highlights
Accepted: 16 November 2021The methodology of clinical trials in oncology is continuously adapting to the rapid development of new targeted agents [1]
Excluding the arms closed due to early termination of drug development or lack of efficacy, the overall response rate (ORR) observed ranged from 50% (10/20, 95% CI: 28.0–71.9) of savolitinib monotherapy to 24% (6/25, 95% CI: 7.3–40.7) of adavosertib/paclitaxel combination
Despite their intrinsic limitations and the difficulties related to their planning, coordination and conduction, represent a great opportunity in biomarker-driven clinical research to accelerate drug development in “precision oncology”
Summary
The methodology of clinical trials in oncology is continuously adapting to the rapid development of new targeted agents [1] The spread of these biomarker-driven therapies led to a “rethinking” of the classic design of clinical trials, considering that the more the number of subgroups of patients with a specific molecular or genomic biomarker increases, the more the size of subgroups decreases [2]. The known cost of genomic or molecular profiling must be added to the cost of planning and conducting different, parallel trials in each small patients’ subgroup, identified by a genomic/molecular alteration that is supposed to be targeted by the drug under evaluation [5] The feasibility of such a strategy is weakened by the difficulty of an efficient selection and enrollment process of subjects that fit all (usually many) protocol criteria without waste [7,8]. Basket and platform trials are included under this definition [10]
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