PLZ reports personal fees from Verastem, Merck Sharp & Dohme, Eusapharma, Sanofi, ADC Therapeutics, Celltrion, Gilead, Janssen-Cilag, Bristol-Myers Squibb, Servier, Sandoz, Immune Design, Celgene, Portola, Roche, and Kyowa Kirin, outside of the submitted work. Stat Med. 2019;142(3):45562. Figure1 shows flow diagram (PRIMA) of the literature search and study selection process. Chu Y, Yuan Y. Spatial two-stage designs for phase ii clinical trials. Di Nunno V, et al. Santoni M, et al. WebARTICLE Clinical Trials 2011; 8: 260269 Quantitative evaluation of single-arm versus randomized phase II cancer clinical trials Gregory R Ponda,b and Saqib Abbasia Background There is a debate among cancer researchers about the use of single-arm or randomized phase II clinical trial designs; however, there is limited published 4). Loncastuximab tesirine has substantial single-agent antitumour activity and produces durable responses with an acceptable safety profile, potentially offering a new therapeutic option for heavily pretreated patients with relapsed or refractory DLBCL. Regardless that more than 75% trials mentioned all key input parameters, many studies (17/29, 59%) failed to provide at least one key output of sample size calculation results of the number of samples of both stages (\({n}_{1}, n\)) and the treatment rejection numbers of the first stage and both stages (\({r}_{1}, r\)). A Bayesian basket trial design using a calibrated Bayesian hierarchical model. Using four key input parameters of two types of error (\(\alpha , \beta\)) and two hypothesis rates of unacceptable maximum response rate of historical control (\({p}_{0}\)) and acceptable minimum response rate of study expectation (\({p}_{1}\)), we can implement the sample size calculation of the two-stage designs. Recent research reported that the success rate in proceeding from Phase 2 to Phase 3 was the lowest among all three rates of Phase 1 to 2, Phase 2 to 3, and Phase 3 to approval (e.g., 29.7%, 20.3%, and 35.5% for oncology and 35.2%, 27.4%, 59% for overall) [2]. 1996 Oct;74(8):1317-20. doi: 10.1038/bjc.1996.537. Cancer Med. Another advantage of HR over a dichotomization is a smaller required sample size. In this phase 2 study, we demonstrated that treatment with single-agent PD-1 inhibitor was safe and associated with a 3-month OS of 60% in a heavily pre-treated There was no language restriction, but only complete papers published in peer-reviewed journals were considered. 2019 Jul 2;10(42):4255-4261. doi: 10.18632/oncotarget.26981. 2022 Oct;23(10):1457-1476. doi: 10.1007/s11864-022-01011-w. Epub 2022 Sep 22. Using Nonetheless, none has examined the usage for published articles that had applied the two-stage designs in Phase 2 single-arm trials in brain tumor. 2012;48(2):25362. The primary endpoint was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). J Neurooncol. For general information, Learn About Clinical Studies. Multicenter Phase II Study of Lenalidomide in Relapsed or Recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002. MH reports grants from Takeda, Spectrum Pharmaceuticals, Astellas Pharma, and personal fees from Janssen, Incyte Corporation, ADC Therapeutics, Celgene, Pharmacyclics, Omeros, AbGenomics, Verastem, TeneoBio, Sanofi Genzyme, BeiGene, and AstraZeneca, outside of the submitted work. 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. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Cancer 124, 2135 (2018). Optimized image-based surrogate endpoints in targeted therapies for glioblastoma: a systematic review and meta-analysis of phase iii randomized controlled trials. If the therapy shows sufficient responses with the first stage data, the study will be continued for additional second stage with more patients to finalize the interim tests on the hypothesis that the therapy has sufficient biological activity to be able to advance for larger phase 3 randomized trials [6, 12]. 2021 Dec;21(12):1313-1320. doi: 10.1080/14737140.2021.1988853. Childs Nerv Syst. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. and transmitted securely. Bayesian single-arm phase II trial designs with time-to-event endpoints. J Neurooncol. Copyright 2020 Friends of Cancer Research. Part of Funding: Treatment-emergent adverse events (TEAEs) were manageable. 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. 1982;38(1):14351. Better understanding on the study drug information and targeted molecular information might help the understanding of why the two-stage trials had been terminated after the stage 1 and ineffective after successful completion of both stages. 2012;4(4):799801. PMC J Clin Oncol. 2022 Dec;17(6):524-532. doi: 10.1159/000526431. Accessibility 2015;34(16):240316. Int Stat Rev/Revue Int de Stat. Article OPTIM-ARTSAn adaptive phase II open platform trial design with application to a metastatic melanoma study. The Follow-Up period ends 2 years after End of Treatment. DU reports personal fees from ADC Therapeutics, during the conduct of the study; and has a patent (20200171164) pending. 1961;13:34653. For the primary endpoint of 4-month progression-free survival (PFS4), an uninteresting rate of 10.9% obtained from historical controls and an anticipated rate of 28.9% were assumed. and transmitted securely. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. Polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed or refractory follicular lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study. Such a study design may not be suitable for immunotherapy cancer trials, when both long-term survivors (or even cured patients from the disease) and delayed treatment effect are present, because exponential distribution is not appropriate to describe such data and consequently could lead to severely underpowered trial. 2022 Dec 26;56:101779. doi: 10.1016/j.eclinm.2022.101779. Estimation of clinical trial success rates and related parameters. Simons optimal design for a one-sided significance level of 0.05 and a power of 0.80 includes 11 patients in the first stage. When there is uncertainty among endpoints as a surrogate for OS, several primary endpoints can be employed together. statement and A better way to avoid the potential issues is to use a hazard ratio (HR). The https:// ensures that you are connecting to the Lassen U, et al. This site needs JavaScript to work properly. 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. Keywords: In safety studies, a main concern is that there may be too many patients who experience an adverse event. An International, Single-Arm, Multicenter Phase 2 Trial. Cancers (Basel). J. Neurooncol. Bethesda, MD 20894, Web Policies J Nat Cancer Inst. Front Oncol. Clipboard, Search History, and several other advanced features are temporarily unavailable. However, we should acknowledge there exist heterogeneities when we borrow the historical control information from other published studies due to different population conditions and quality of supportive care. Kalpathy-Cramer J, et al. WebThe trial ended after accrual completion; the database lock was Dec 31, 2019. 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. Phase II clinical trials: issues and practices. Treatment-emergent adverse events (TEAEs) were manageable. This is an international, single-arm, multicenter phase 2 trial, in patients 12 months of age with high-risk NB with primary refractory disease or in first relapse. The .gov means its official. 2021 Jun;22(6):741-742. doi: 10.1016/S1470-2045(21)00191-1. eCollection 2021. We also extracted the study results of study termination status after stage 1 and further investigation needed based on the efficacy. 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 Eastern Cooperative Oncology Group. Oncoimmunol. Before Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. MeSH A systematic review of surrogate endpoints (SEPs) for overall survival (OS) in metastatic colorectal cancer mCRC. The rapid trials and ethical reasons generally lead the single-arm trials to be performed with interim analyses for possible early termination of the trials. Federal government websites often end in .gov or .mil. This site needs JavaScript to work properly. 2004;60(2):48290. Spatial Two-stage Designs for Phase II Clinical Trials. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. Ramchandren R, Johnson P, Ghosh N, Ruan J, Ardeshna KM, Johnson R, Verhoef G, Cunningham D, de Vos S, Kassam S, Fayad L, Radford J, Bailly S, Offner F, Morgan D, Munoz J, Ping J, Szafer-Glusman E, Eckert K, Neuenburg JK, Goy A. EClinicalMedicine. 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]. A treatment cycle is 21 days. Webmultiple myeloma: a multicenter, single-arm phase 2 trial Thilo Zander 1 , Thomas Pabst 2 , Smi Schr 3 , Stefan Aebi 1,2 , Ulrich Mey 4 , Urban Novak 2 , Erika Lerch 5 , Galle Rhyner Agocs 6 , 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. Most frequently used population was adult patients with recurrent glioblastoma. Nat Med. Rubinstein LV, et al. 2021;20(6):123548. HHS Vulnerability Disclosure, Help Temozolomide (TMZ) was mostly used for combination therapeutic drugs (n=7 with pegylated liposomal doxorubicin (PLD), O6-benzylguanine (O6B), irinotecan (IRI), decitabine (DAC), Dendritic (DEN), Nintedanib (NIN), and Atorvastatin (ATO)) while Bevacizumab (BEV) was second mostly used for combination drugs (n=3 with temsirolimus (TEM), Ponatinib (PON), and Evofosfamide (EVO)). Neuro Oncol. Another option of two-stage designs is admissible design or spatial design, which came from an idea Can we find a good alternative design between the minimax and optimal design. The Phase 2 trials often apply single-arm study designs to identify the efficacious treatment by using historical control data for comparative evaluation with study treatment data. Before CNS Drugs. 2021;39(1):22631. MeSH 2013;24(4):11129. 2018;7(4):e1412901. Please enable it to take advantage of the complete set of features! 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