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Tumor Discovery Practice and consideration of master protocol design

Table 2. (Continued)
Trial NCT number Description Design Intervention Sample size Primary endpoint
4. 1-year tumor
control-Phase II
5. Rate of pathologic
complete
response-Gastric
UMBRELLA-II [13] NCT04351204 Combination of a basket Open-label, Techniques/ Per sub-study, a Feasibility
and umbrella trial to non-randomized, software for maximum of 20
evaluate the feasibility single-group MR-guided patients can be
of various in-house assignment trial adaptive enrolled. No formal
developed techniques/ radiotherapy sample size calculation
software on the MR-Linac with the was performed
in various tumor sites MR-Linac because this is not
a hypothesis-driven
research. Rather, it is
based on the needs
of demonstrating
feasibility of
techniques/software
CONCORDE [39] NCT04550104 Platform trial using the Phase I, 1. Radiotherapy 200 planned for whole Dose limiting toxicities
TiTE CRM design to find multi-institution, only study
the RP2D of each DNA multi-arm, 2. Olaparib+
damage response inhibitor open-label, radiotherapy
in combination with randomized trial 3. AZD1390+
conventional radiotherapy radiotherapy
in non-small cell lung cancer
MRI: Magnetic resonance imaging; CIVO: Comparative in vivo oncology; SMART: Stereotactic magnetic resonance-guided adaptive radiation therapy;
MR: Magnetic resonance
We believe that the increased efficiency in trial Among the master protocol trials of COVID-19
administration and infrastructure, the most significant published so far, the most common trial design is the
advantage of a master protocol trial design, will facilitate platform trial, as it is relevant to the current need of
the complex systematic evaluation of innovations in developing COVID-19 drugs rapidly. In these trials, multiple
oncology devices which is of great importance to patients, interventions for COVID-19 are evaluated in different sub-
users, vendors, and society. studies with the addition and removal of interventions
based on planned interim analyses, which can accelerate
5. Master protocol trials in COVID-19 drug development and maximize the information obtained
The COVID-19 pandemic threatens global security and from the research effort. For example, RECOVERY is a
the economy. Although safe and effective vaccines for platform trial to evaluate the effects of potential treatments
[40]
COVID-19 have been developed and distributed, there in patients admitted to hospitals with COVID-19 .
is still a need to evaluate multiple treatments in clinical Consequently, effective treatment (dexamethasone) was
trials. However, unique challenges posed by COVID-19 quickly established in patients admitted to hospitals with
have exposed inadequacies in the conventional phased COVID-19, which immediately changed clinical practice.
investigational therapeutic development paradigm. To Furthermore, compared with conducting separate stand-
address the COVID-19 public health emergency, FDA alone trials, conducting a master protocol trial can increase
issued a guidance in 2019, which describes the FDA’s data quality and efficiency through shared infrastructure
current recommendations to sponsors of master protocols and reduce overall sample size by sharing a control arm.
evaluating drugs for the treatment or prevention of These efficiencies are of particular importance in the public
COVID-19 . The master protocols can unify resources health emergency with a critical need for efficient therapies,
[2]
and efforts for clinical research worldwide to initiate and such as the current COVID-19 pandemic. Therefore,
coordinate COVID-19 clinical trials, which accelerate the we expect master protocol trials to continue to play an
treatment evaluation of COVID-19. Here, we summarize important role in addressing the public health needs created
the key information of several representative master by the current COVID-19 pandemic, and other emerging
protocol trials in COVID-19 in Table 3. infectious diseases that might occur in the future.

Volume 2 Issue 2 (2023) 10 https://doi.org/10.36922/td.342