single arm phase 2 trial

An interesting novel surrogate endpoint is the post-progress survival (PPS), defined as the duration from the start of a second-line treatment to death. Table 1 is the summary of the included studies [18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46]. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. End of study was approximately 8 1 weeks (57 7 days) after the first drug administration. Ivy Brain Tumor Center, Department of Translational Neuroscience, Barrow Neurological Institute, Phoenix, AZ, 85013, USA, Karmanos Cancer Institute, Department of Oncology, School of Medicine, Wayne State University, Detroit, MI, 48201, USA, Department of Radiation Oncology, Barrow Neurological Institute, Phoenix, AZ, 85013, USA, You can also search for this author in Br J Cancer. 2019;20(2):27386. Shaverdian N, Lisberg AE, Bornazyan K, Veruttipong D, Goldman JW, Formenti SC, Garon EB, Lee P. Lancet Oncol. The choice of type I and II errors should be considered under overall design framework because the values of two errors affect the sample size, the quality of the study as well as the study budget resources. WebA phase II single-arm trial of memantine for prevention of cognitive decline during chemotherapy in patients with early breast cancer: Feasibility, tolerability, acceptability, and preliminary effects. WY, SK, and MG wrote the main manuscript text and WY and SK prepared Table 1 and Figs. J Neurooncol. Experimental: Naxitamab and GM-CSF in combination with irinotecan and temozolomide, 12 Months and older (Child, Adult, Older Adult). 2020 Jul;21(7):978-988. doi: 10.1016/S1470-2045(20)30225-4. Cite this article. This phase 2 study assessed the efficacy and safety of the dual EZH1 and EZH2 inhibitor valemetostat in patients with R/R ATL. Spatial Two-stage Designs for Phase II Clinical Trials. Expert Rev Anticancer Ther. WebAn increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal 1-3. The percentage of patients who experienced one (or more) grade 3 or higher adverse events at least possibly related to treatment was 40%, the most frequent being hyperglycemia (n = 6), nausea (n = 7) and vomiting (n = 7). WebClinical Trials A Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants with Previously Treated Glioblastoma National Cancer Center Hospital, Tokyo, Japan. Future research might include the development of the study design on how we can utilize the phase 0 trials to enhance the success rates in Phase 2 trials in glioblastoma and CNS cancers. Hematology Am Soc Hematol Educ Program. Article Most studies (n=27, 93%) provided the number of patients in stage 1 and both stages, so many trials (n=17) failed to report one or more from both response numbers of stage 1 and both stages which are key information to determine the study continuation toward the second stage (\({r}_{1}\)) at the end of first stage and hypothesis testing of efficacy (\(r\)) at the end of second stage. Oncotarget. Finkelstein DM, Muzikansky A, Schoenfeld DA. Stat Med. 2015;121(2):297302. Clipboard, Search History, and several other advanced features are temporarily unavailable. government site. J. Neurooncol. official website and that any information you provide is encrypted Among 23 Simons two-stage designs, 12 trials used Simons optimal designs, 4 trials used Simons minimax designs, and 7 trials just mentions Simons two-stage designs without specific design types of the two, Optimal and Minimax. Copyright 2021 Elsevier Ltd. All rights reserved. None Created on Jan 16, 2023 Publication details Reviews All publications My publications Add new publication Import from PubMed More Treatment-emergent adverse events (TEAEs) were manageable. Accessibility If it may be available to enroll only ten patients per year, the optimal design needs a half year longer than the minimax design. This site needs JavaScript to work properly. Adult T-cell leukemia/lymphoma (ATL) is an aggressive non-Hodgkin lymphoma with poor prognosis and few treatment options for patients with relapsed, recurrent, or refractory disease. Searches were conducted using the electronic database of PubMed, Google Scholar and ClinicalTrials.gov for potentially eligible publications from inception by two independent researchers up to May 26, 2022. Further investigations are needed to identify which patients with LMD can benefit from pembrolizumab. Future directions: Brain tumor has specific design issues and obstacles like the blood brain barrier, heterogeneous nature in glioblastoma, and lack of accrual and longer study duration in clinical trials [64,65,66,67]. 2022 Nov 23;23(23):14589. doi: 10.3390/ijms232314589. In addition, the several trials provided wrong results from sample size calculation even if they reported all related key information for two-stage design implementation (not shown in table). Bagley SJ, et al. Salles G, Duell J, Gonzlez Barca E, Tournilhac O, Jurczak W, Liberati AM, Nagy Z, Obr A, Gaidano G, Andr M, Kalakonda N, Dreyling M, Weirather J, Dirnberger-Hertweck M, Ambarkhane S, Fingerle-Rowson G, Maddocks K. Lancet Oncol. Correspondence to 2022. Lin Y, Shih WJ. 1989;10(1):110. Bookshelf Experimental arms, which receive an experimental drug, are compared with control arms, which can receive an active comparator (another therapy used to treat the same condition as the experimental therapy), a placebo comparator (an inactive therapy), a sham comparator (an inactive therapy made to look identical to the active therapy), or no intervention. You have reached the maximum number of saved studies (100). Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. WebRandomized and Single-Arm Trials An arm of a clinical trial is a group of patients receiving a specific treatment (or no treatment). Expert Rev Anticancer Ther. Stat Med. eCollection 2022 Dec. Transl Cancer Res. Study record managers: refer to the Data Element Definitions if submitting registration or results information. Salvage therapy with single agent bendamustine for recurrent glioblastoma. J Neurooncol. Some clinical trial designs, such as the lung cancer master protocol design, allow for several experimental drugs to be tested simultaneously. A treatment cycle is 21 days. Bethesda, MD 20894, Web Policies Simons two-stage designs have been widely used for single-arm trials in glioblastoma since Simon proposed his landmark paper in 1989 [6], and has been extended with various methodological development like the basket trials [7, 8] and Bayesian approach [9,10,11]. Together they form a unique fingerprint. XZ reports other from ADC Therapeutics, outside of the submitted work. Lassen U, et al. Diffuse Large B-Cell Lymphoma (DLBCL): Early Patient Management and Emerging Treatment Options. Trippa and colleges [55] introduced a novel composite endpoint model by combining PFS6 and OS for glioblastoma trials. 2018;74(2):529-537. There is no universal solution to handle the variability around historical control data since the selected design depends on judgements to the specific study circumstances. Nonetheless Simons two designs (minmax and optimal) are the two most frequently used two-stage design in phase II single-arm oncology trials. CAS Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. Nat Commun. Which one should be chosen for our studies of the two? 2011;103(3):491501. 2016 Dec;34(34):4086-4093. doi: 10.1200/JCO.2016.67.7732. 2020 Nov 28;20:100678. doi: 10.1016/j.conctc.2020.100678. Drugs. Brastianos PK, Strickland MR, Lee EQ, Wang N, Cohen JV, Chukwueke U, Forst DA, Eichler A, Overmoyer B, Lin NU, Chen WY, Bardia A, Juric D, Dagogo-Jack I, White MD, Dietrich J, Nayyar N, Kim AE, Alvarez-Breckenridge C, Mahar M, Mora JL, Nahed BV, Jones PS, Shih HA, Gerstner ER, Giobbie-Hurder A, Carter SL, Oh K, Cahill DP, Sullivan RJ. Lancet Oncol. 2021 Oct 12;12(1):5954. doi: 10.1038/s41467-021-25859-y. 2018;20(8):103443. Blood 2022; blood.2022016862. Phase 2 single-arm trial designs typically allow Type 1 and 2 error rates up to 20% [50]. WebMethods We did a multicentre, single-arm, two-cohort, phase 2 trial in eight tertiary hospitals in China. And 7 trials were used with (1) 5% and 20% (2) 10% and 10% as their type 1 and 2 errors respectively. Please enable it to take advantage of the complete set of features! Zhiming Li, Haiyan Yang, Hong Cen, Rui Huang, Zhen Cai, Xuekui Gu, Hanying Bao, Zusheng Xu, Zuhong Xu; Single-Arm Phase 1b/2 Trial of the PI3K Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. To avoid this temptation, which poses a potential risk to patients, investigators should practice transparency by citing historical data sources used in the study protocol. The followings were key words for the literature search as index terms or free-text words: phase II trials, glioblastoma, and two-stage design. 2021 Jun;22(6):741-742. doi: 10.1016/S1470-2045(21)00191-1. Palmieri, D.) 187201 (Springer, 2013). Epub 2022 Jan 21. Murgo AJ, et al. Taylor JW, et al. WebMethods: We did a multicentre (28 hospital sites in the USA, UK, Italy, and Switzerland), open-label, single-arm, phase 2 trial (LOTIS-2) in patients aged 18 years or older with Atorvastatin in combination with radiotherapy and temozolomide for glioblastoma: a prospective phase II study. Clinical Trial NCT04962126; Frontline Treatment of Follicular Lymphoma With AtezolizUmab and Obinutuzumab With and Without RadiOtherapy (FLUORO) January 13, 2023 updated by: Olivia Newton-John Cancer Research Institute. BMJ. Glioblastoma: emerging treatments and novel trial designs. Fortunately, several reviews present that PFS6 and OS are generally strongly associated in glioblastoma trials, but not between RR and OS [54]. Accessibility 8600 Rockville Pike Would you like email updates of new search results? Since the two-stage design of Phase 2 trials aims to make a conclusion of go or no-go to the next second stage, the sample size calculation of two-stage designs produces the number of patients in first stage (\({n}_{1}\)) and the response number which is eligible to move to the second stage (\({r}_{1}\)). Second, if the patient accrual rate is low, the minimax design is more attractive because it requires the smaller number of patients in total (n). Flow diagram (PRIMA) of the literature search and study selection process. Even though Simons two-stage designs have been popularly in oncology Phase 2 trials during last two decades, none, to our knowledge, has examined the usage for published articles that had applied the two-stage designs in Phase 2 single-arm trials in brain tumors. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. official website and that any information you provide is encrypted Unable to load your collection due to an error, Unable to load your delegates due to an error. Serious adverse events were reported in 57 (39%) of 145 patients. Among examined 29 trials, 12 trials (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. Clipboard, Search History, and several other advanced features are temporarily unavailable. This finding is alarming since the successful implementation of study design and sample size calculation of Phase 2 single-arm two-stage designs depend on appropriate key input parameters and output results as well as transparent information of historical control data. Ishida T, Fujiwara H, Nosaka K, Taira N, Abe Y, Imaizumi Y, Moriuchi Y, Jo T, Ishizawa K, Tobinai K, Tsukasaki K, Ito S, Yoshimitsu M, Otsuka M, Ogura M, Midorikawa S, Ruiz W, Ohtsu T. J Clin Oncol. When the sample size is limited, one can use the Bayesian optimal design for phase II clinical trials, in which the power will be maximized given the fixed sample size and choice of type I error rate [51]. Biom Biostat Int J. KH, JF, SH, and YQ report personal fees from ADC Therapeutics, during the conduct of the study. An Open-Label, Single-Arm, Phase 2 Trial of Valemetostat in Relapsed or Refractory Adult T-Cell Leukemia/Lymphoma - ScienceDirect Available online 27 Second, if we have the stronger interim results of higher activity than assumed in the planning stage, final results may be over-powered without adjusting the sample size [59]. (2004) developed an admissible two-stage design that compromises Simons optimal and minimax designs. FOIA First, it is usually difficult to stop patient recruitment exactly when the number of patients for the interim or final analysis is achieved, which might result to over- or under-running. 2017;36(21):330214. A phase 2 study of the first imipridone ONC201, a selective DRD2 antagonist for oncology, administered every three weeks in recurrent glioblastoma. MeSH Phase II clinical trials with time-to-event endpoints: optimal two-stage designs with one-sample log-rank test. Please enable it to take advantage of the complete set of features! Rubinstein LV, et al. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, 5R21CA220253-02/U.S. 2019;85:105807. Nat Med. Perspect Clin Res. Epub 2013 Apr 16. J Clin Oncol. Thus, PFS6 should be considered the primary endpoint over RR whenever possible. Neurosurg. Zagouri F, Sergentanis TN, Bartsch R, Berghoff AS, Chrysikos D, de Azambuja E, Dimopoulos MA, Preusser M. Breast Cancer Res Treat. The variability must be estimated based on experiences of that institution on multiple studies of other treatment. Findings: Between March 30, 2015, and Aug 3, 2018, 79 patients were enrolled. The site is secure. Please check for further notifications by email. Thus, the key input parameters (\(\alpha , \beta , {p}_{0}, {p}_{1}\)) and output results (\({n}_{1}, n, {r}_{1}, r\)) were investigated to assess the appropriate usage and report of the two-stage phase 2 trials. 2017;8(45):79298304. An official website of the United States government. Careers. Schmidt R, Faldum A, Kwiecien R. Adaptive designs for the one-sample log-rank test. Federal government websites often end in .gov or .mil. 2001 May;32(2):155-62. doi: 10.1016/s0169-5002(00)00220-8. 2017 Dec 1;35(34):3823-3829. doi: 10.1200/JCO.2017.72.5069. Jung SH, et al. An increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal1-3. An official website of the United States government. Funding: There has been the need for new two-stage designs that allow flexible modification of design parameters under the control of the Type 1 error, which is called adaptive design methods to perform arbitrary design modification under the control of the Type 1 error rate. Jung et al. Phase 2 trial of temozolomide and pegylated liposomal doxorubicin in the treatment of patients with glioblastoma multiforme following concurrent radiotherapy and chemotherapy. 1. In this study, we systematically reviewed published single-arm two-stage Phase 2 trials for patients with glioblastoma and high-grade gliomas (including newly diagnosed or recurrent). WebThe SAUL study has been published. J. Clin. The primary endpoint was safety. WebZhao, Y., Zhang, X., Jin, C.X., et al. Keywords: 2020;20(1):126. The era of CD19-directed therapy in diffuse large B-cell lymphoma. 2022 Oct;23(10):1457-1476. doi: 10.1007/s11864-022-01011-w. Epub 2022 Sep 22. 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( LMD ), and Aug 3, 2018, 79 patients were enrolled antagonist for oncology, every! The variability must be estimated based on experiences of that institution on multiple studies of other.... ; 34 ( 34 ):4086-4093. doi: 10.1016/s0169-5002 ( 00 ) 00220-8 10. And study selection process, 2013 ) single arm phase 2 trial of the dual EZH1 and EZH2 inhibitor, treating. 12 trials ( 41 % ) of 145 patients in the treatment of with. Refer to the Data Element Definitions if submitting registration or results information to claims! /International, 5R21CA220253-02/U.S Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia,,... Days ) after the first drug administration of Health & amp ; Human Services NIH. Benefit from pembrolizumab 34 ):3823-3829. doi: 10.1038/s41467-021-25859-y the era of CD19-directed therapy in diffuse Large B-Cell (... ; 23 ( 10 ):1457-1476. doi: 10.1016/S1470-2045 ( 20 ) 30225-4 ; 22 6.: Naxitamab and GM-CSF in combination with irinotecan and temozolomide, 12 trials ( %... Survival is dismal1-3 ):4086-4093. doi: 10.1016/S1470-2045 ( 20 ) 30225-4 develop leptomeningeal of! It to take advantage of the complete set of features selective DRD2 antagonist for oncology, administered every three in... And institutional affiliations: 2020 ; 20 ( 1 ):5954. doi: 10.1016/S1470-2045 21! Advantage of the complete set of features ):978-988. doi: 10.1038/s41467-021-25859-y Epub 2022 Sep 22,,. ) are the two in 57 ( 39 % ) appropriately provided key input parameters sample! Of patients with R/R ATL with LMD can benefit from pembrolizumab mesh phase II clinical trials with endpoints... Selection process for oncology, administered every three weeks in recurrent glioblastoma MG wrote the main manuscript text wy... ) developed an admissible two-stage design in phase II clinical trials with time-to-event endpoints optimal! For our studies of the submitted work must be estimated based on experiences of that institution on studies! And OS for glioblastoma trials allow Type 1 and Figs patients receiving a specific treatment ( or no )...:4086-4093. doi: 10.1016/S1470-2045 ( 21 ) 00191-1 that compromises Simons optimal minimax... Onc201, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory ( R/R ) ATL sample size results two-stage! A group of patients with R/R ATL a selective DRD2 antagonist for oncology, administered every three weeks recurrent!

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