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Tumor Discovery Practice and consideration of master protocol design

fundamental problems in traditional trials have become Supervision: Kang Li, Fengyu Sun, Yan Hou
apparent and difficult to handle. Therefore, master Writing – original draft: Xinwen Zhong, Jiali Song, Yuhong Lu
protocols should be prudently used when they are Writing – review & editing: Jike Huang, Yipei Yu, Zhilin
unavoidable for scientific reasons. It is unethical and Liu, Xuyuan Quan, Nana Chen
inappropriate to consider master protocols as a vehicle
that can simplify authorization or shorten review Ethics approval and consent to participate
timelines. The abuse of over-complex clinical trial designs Not applicable.
might result in unethical conduct of studies and weaken
regulatory independence. In practice, master protocol Consent for publication
design and execution require careful consideration of Not applicable.
time and resources for establishing trial infrastructure,
predefining planning, and collaborating among different Availability of data
parties involved in the conduct to agree on trial details.
Therefore, a master protocol should be carefully designed Not applicable.
and restricted to ensure trial subject safety, data integrity, References
or quality of trial conduct.
1. FDA, 2022, Master Protocols: Efficient Clinical Trial
Nevertheless, it has been argued that master protocol Design Strategies to Expedite Development of Oncology
trials could enhance clinical trial efficiency and reduce trial Drugs and Biologics Guidance for Industry. Silver Spring,
time and cost from a long-term perspective. First, master Maryland: The United States Food and Drug Administration.
protocols increase the benefits of patients in clinical trials 2. FDA, 2019. COVID-19: Master Protocols Evaluating Drugs
because these designs aim to treat patients with the most and Biological Products for Treatment or Prevention
rational therapy based on their characteristics. Besides, Guidance for Industry. Silver Spring, Maryland: The United
master protocols are long-term with trial infrastructure States Food and Drug Administration.
shared and common standardized operating procedures 3. Hyman DM, Puzanov I, Subbiah V, et al., 2015, Vemurafenib
established between sub-studies. Therefore, they can in multiple nonmelanoma cancers with BRAF V600
collect a large amount of high-quality data, and recruit mutations. N Engl J Med, 373(8): 726–736.
and train clinical trial staff into secure roles. In addition,
master protocols allow adding a new therapeutic discovery 4. Demetri GD, Paz-Ares L, Farago AF, et al., 2018, Efficacy and
safety of entrectinib in patients with NTRK fusion-positive
after a clinical trial begins, rather than launching a new tumours: Pooled analysis of STARTRK-2, STARTRK-1, and
clinical trial, and better adopting the new changes in ALKA-372-001. Ann Oncol, 29: 175–175.
clinical practices. Finally, as precision medicine develops,
the therapies become more and more stringent to evaluate 5. Renfro LA, Sargent DJ, 2017, Statistical controversies in
rapidly, there is no alternative but to move forward with clinical research: basket trials, umbrella trials, and other
current research efforts to simultaneously test multi- master protocols: A review and examples. Ann Oncol,
28(1): 34–43.
treatments or multi-diseases within master protocols.
6. Woodcock J, LaVange LM, 2017, Master protocols to study
Acknowledgments multiple therapies, multiple diseases, or both. N Engl J Med,
377(1): 62–70.
None.
7. Park JJ, Hsu G, Siden EG, et al., 2020, An overview of
Funding precision oncology basket and umbrella trials for clinicians.
CA Cancer J Clin, 70(2): 125–137.
This work was supported by the National Natural Science
Foundation (grant number: 82173615) of China. 8. Barker AD, Sigman CC, Kelloff GJ, et al., 2009, I-SPY
2: An adaptive breast cancer trial design in the setting
Conflict of interest of neoadjuvant chemotherapy. Clin Pharmacol Ther,
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The authors declare that they have no known competing 9. Herbst RS, Gandara DR, Hirsch FR, et al., 2015, Lung master
financial interests or personal relationships that could have protocol (Lung-MAP)-a biomarker-driven protocol for
appeared to influence the work reported in this paper. accelerating development of therapies for squamous cell lung
cancer: SWOG S1400. Clin Cancer Res, 21(7): 1514–1524.
Author contributions
10. Hirakawa A, Asano J, Sato H, et al., 2018, Master protocol
Conceptualization: Jiali Song, Zhiwei Rong, Fengyu Sun, trials in oncology: Review and new trial designs. Contemp
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Volume 2 Issue 2 (2023) 17 https://doi.org/10.36922/td.342