single arm phase 2 trialsingle arm phase 2 trial

Terms and Conditions, eCollection 2021. official website and that any information you provide is encrypted J Clin Oncol. Pellegatta S, et al. 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 Adaptive two-stage designs in phase II clinical trials. Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. -, Wang, N., Bertalan, M. S. & Brastianos, P. K. Leptomeningeal metastasis from systemic cancer: review and update on management. FOIA 2021 Jun;22(6):741-742. doi: 10.1016/S1470-2045(21)00191-1. The underestimation rate of p0 was ranged from 0.1 (i.e., 10% reduction) to 0.5 (i.e., 50% reduction). TACE-HAIC Plus Lenvatinib for Patients With Unresectable HCC: an Open-label, Single-arm, Phase 2 Trial (Thalen) The safety and scientific validity of this study Stat Med. WebZhao, Y., Zhang, X., Jin, C.X., et al. Neurosurg. To illustrate the effect of underestimated historical control on the study power, we carried out a simulation study as follows. WebThis single-arm, phase I trial evaluated NHS-IL12 12 g/kg SC q2w or 16.8g/kg SC q2w in patients with metastatic solid tumors. Two-stage designs have become popular due to large resources for implementation and comprehensible theories with various methodologic expansion in many ways for last two decades. Cerebrospinal fluid neurofilament light chain as a potential prognostic biomarker for leptomeningeal metastasis. Secondary objectives included toxicity, response rate and time to intracranial or extracranial disease progression. The choice of type I and type II errors is highly important since researchers need to assure that potentially effective therapy is not abandoned and at the same time the insignificant studies with very small marginal effects should not be advanced to subsequent phase III studies. Anticancer Res. Trials involving several arms, or randomized The most common grade 3 or higher treatment-emergent adverse events were neutropenia (37 [26%] of 145 patients), thrombocytopenia (26 [18%]), and increased gamma-glutamyltransferase (24 [17%]). 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. Semin Oncol. Pharm Stat. Exploration of modified progression-free survival as a novel surrogate endpoint for overall survival in immuno-oncology trials. The primary endpoint was met with a centrally reviewed ORR of 48.0% (90% CI, 30.5% to 65.9%), including 5 complete and 7 partial remissions. 2020;323(9):84453. 8600 Rockville Pike Rubinstein LV, et al. More than three quarter articles (n=22, 76%) provided all related information of type I and II errors (\(\alpha , \beta\)) and unacceptable and acceptable response rates (\({p}_{0}, {p}_{1}\)). Blood 2022; blood.2022016862. Pan E, et al. In this manner, the two-stage designs allow stopping of a futile trial early. MeSH 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. Manage cookies/Do not sell my data we use in the preference centre. Patients received 200 mg of pembrolizumab intravenously every 3 weeks until definitive progression or unacceptable toxicity. The median follow-up of surviving patients was 6.3 months (range, 2.2-12.5 months). Among 29 trials, only three has been completed for both stages and two studies have shown the efficacy. 1. Read our, ClinicalTrials.gov Identifier: NCT04560166, Interventional For good study design with phase II trials, investigators should maintain low level of type I and II errors. The synonyms and closely related words include phase 2 for phase II trials, GBM or high-grade glioma for glioblastoma, and 2-stage, Simon, Fleming or Gehan for two-stage design. Pharm Stat. Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma. Epub 2022 Aug 10. 2015;34(6):1031-1040. Re-formulating Gehan's design as a flexible two-stage single-arm trial. Fangusaro J, et al. Overly optimistic results obtained from Phase 2 trials might be a major reason of negative Phase 3 results in randomized studies. Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. 2018 Sep;17(5):541-554. doi: 10.1002/pst.1878. Berry SM, et al. FOIA official website and that any information you provide is encrypted This site needs JavaScript to work properly. Copyright 2023 by American Society of Hematology. 2009;45(5):7416. Unlike a survival rate at a specific time point, a HR is not a point estimate and uses all the information in the entire survival curve. A prospective phase II single-institution trial of sunitinib for recurrent malignant glioma. Kummar S, et al. PLoS One. The https:// ensures that you are connecting to the This phase 2 study assessed the efficacy and safety of the dual EZH1 and EZH2 inhibitor valemetostat in patients with R/R ATL. The .gov means its official. The most widely used endpoints were PFS6 (n=18) and ORR (n=8) in Phase 2 single-arm trials. Several important topics related to the design issues will be followed to handle the design issues by increasing the precision of efficacy from targeted therapeutic trials of Phase 2 two-stage designs in brain tumor. 2016 Dec;34(34):4086-4093. doi: 10.1200/JCO.2016.67.7732. Kaley TJ, et al. J. Clin. Shi YK, Hong XN, Yang JL, Xu W, Huang HQ, Xiao XB, Zhu J, Zhou DB, Han XH, Wu JQ, Zhang MZ, Jin J, Ke XY, Li W, Wu DP, Yang SM, Du X, Jia YQ, Liu AC, Liu DH, Shen ZX, Zhang LS, James L, Hellriegel E. Chin Med J (Engl). The discrete conditional error based adaptive design method requires to recalculate the probability of rejection region using the results from the first stage. 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]. Accessibility 1990;9(3):21528. We also sought to understand how these two-stage trials have been implemented, and discussion of potential design issues which we hope will be helpful for investigators work with Phase 2 clinical trials in rare and high-risk cancer studies including Neuro-Oncology. 2021 Jan;20(1):117-128. doi: 10.1002/pst.2060. Let us assume that the result of a two-stage design indicates 18 and 23 in total patients for the minimax and optimal respectively. Federal government websites often end in .gov or .mil. Valemetostat 200 mg orally once Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase II multicenter clinical trial. Accessibility By doing so, the chance to capture the effectiveness of a treatment can be increased. We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 Your comment will be reviewed and published at the journal's discretion. statement and Federal government websites often end in .gov or .mil. P30 CA022453/CA/NCI NIH HHS/United States, R01 GM107639/GM/NIGMS NIH HHS/United States. Bannerji R, Arnason JE, Advani RH, Brown JR, Allan JN, Ansell SM, Barnes JA, O'Brien SM, Chvez JC, Duell J, Rosenwald A, Crombie JL, Ufkin M, Li J, Zhu M, Ambati SR, Chaudhry A, Lowy I, Topp MS. Lancet Haematol. Geoerger B, et al. 2019 Jan 28;19(1):22. doi: 10.1186/s12874-019-0659-2. In the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. 2019 Mar;20(3):371-382. doi: 10.1016/S1470-2045(18)30812-X. 2020;21(4):47182. A treatment cycle is 21 days. Stat Med. Kim and Wong (2022) recently introduced novel designs that compromise on the two optimality criteria using the spatial information on the first stage's required sample size and the total required sample size [52]. Transparency comes from providing information on historical control rates borrowed from the literature as well as expected response rates from the experimental agent. J Neurooncol. Korean J Radiol. Stat Biopharma Res. Cancer Med. Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. A phase 2 study of the first imipridone ONC201, a selective DRD2 antagonist for oncology, administered every three weeks in recurrent glioblastoma. Adaptive two-stage designs for single-arm phase IIA cancer clinical trials. 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]. doi: 10.1371/journal.pone.0246448. 2007;7(6):32534. As output results, the two-stage designs (Optimal, Minimax, and Admissible designs) produce following key outputs of the number of patients (\({n}_{1}\) and \({n}_{2}\)) for stage 1 and both stages and the rejection numbers (r and \({r}_{1}\)) for both stage 1 and both stages respectively. And 7 trials were used with (1) 5% and 20% (2) 10% and 10% as their type 1 and 2 errors respectively. Some clinical trial designs, such as the lung cancer master protocol design, allow for several experimental drugs to be tested simultaneously. J Chronic Dis. Bethesda, MD 20894, Web Policies Comparison of error rates in single-arm versus randomized phase II cancer clinical trials. All other rights reserved. For the trial, 70 children aged 618 years old with peanut allergies received 12-hour boiled peanuts for 12 weeks, 2-hour boiled peanuts for 20 weeks, and roasted peanuts for 20 weeks, to a target maintenance dose of 12 roasted peanuts daily. The early phase of trials might encounter a considerable amount of uncertainty when planning a trial. 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. Salvage therapy with single agent bendamustine for recurrent glioblastoma. We enrolled patients aged 18 years with HER2-positive breast cancer and newly WebThe trial ended after accrual completion; the database lock was Dec 31, 2019. 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. Clin Cancer Res. Patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity. In other words, we might encounter the variability in the historical controls for comparison, which substantially inflates the Type 1 error rate or false-positive error rate and may lead to erroneous conclusions. Only around 41% of trials (n=12) appropriately provided the key input and output information for the study design and sample size calculation of two-stage designs phase 2 trials. Bayesian hierarchical modeling of patient subpopulations: efficient designs of Phase II oncology clinical trials. 2021 Dec;21(12):1313-1320. doi: 10.1080/14737140.2021.1988853. -, Grossman, S. A. et al. 2022 Dec 7;14(24):6026. doi: 10.3390/cancers14246026. Epub 2021 May 11. 2019;85(6):E96774. Using a 3+3 design, 13 patients with advanced cancer were enrolled and 12 were dose-limiting toxicity (DLT) evaluable. Epub 2022 Jan 21. Zagouri F, Sergentanis TN, Bartsch R, Berghoff AS, Chrysikos D, de Azambuja E, Dimopoulos MA, Preusser M. Breast Cancer Res Treat. Nat Rev Cancer. A common practice in sample size calculation is to assume that the event time in the new treatment follows exponential distribution. 2016;43(1):138. Ott PA, Elez E, Hiret S, Kim DW, Morosky A, Saraf S, Piperdi B, Mehnert JM. Kahl BS, Hamadani M, Radford J, Carlo-Stella C, Caimi P, Reid E, Feingold JM, Ardeshna KM, Solh M, Heffner LT, Ungar D, He S, Boni J, Havenith K, O'Connor OA. Onco Targets Ther. 2020 Aug;26(8):1309. doi: 10.1038/s41591-020-0978-1. 2011;105(3):52330. Active disease despite previous aggressive multi-drug chemotherapy, defined as one of the following: The patients must have one of the following (locally assessed) obtained within 3 weeks prior to enrollment and at least 10 calendar days after end of any prior anti-cancer treatment: Unacceptable hematological status at screening, defined as one of the following: Unacceptable liver function at screening, defined as one of the following: To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next? 11, 561569 (1993). All rights reserved. The clinical trials landscape for glioblastoma: is it adequate to develop new treatments? We extracted disease type and setting, population, therapeutic drug, primary endpoint, input parameters and sample size results from two-stage designs, and historical control reference, and study termination status. J Neurooncol. 2019 Jul 2;10(42):4255-4261. doi: 10.18632/oncotarget.26981. Trippa and colleges [55] introduced a novel composite endpoint model by combining PFS6 and OS for glioblastoma trials. Oncotarget. If the parameters of two-stage designs (\({p}_{0}, {p}_{1}\)) are given, there are infinitely many two-stage designs satisfying the (\({\alpha }^{*}, {\beta }^{*})\) condition. Biostatistics. Third, when expected sample sizes from both designs are close each other, the minimax design may be more appropriate than the optimal design because the minimax design produces the smaller total patients [6]. Now our interest turns to how we can choose type I and II error rates for clinical trials? 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. Naxitamab and GM-CSF will be given for at least 8 cycles. Oncotarget. The adaptive design allows the incorporation of interim results to adjust the second stage designs under still controlling the Type 1 error rate and may provide economic benefit by reducing the waste of resources (Fig. Would you like email updates of new search results? Bethesda, MD 20894, Web Policies 2013 May;139(1):13-22. doi: 10.1007/s10549-013-2525-y. (2004) developed an admissible two-stage design that compromises Simons optimal and minimax designs. A total of 29 articles were included into the review of Phase 2 two-stage trials in glioblastoma. 2022 Dec 26;56:101779. doi: 10.1016/j.eclinm.2022.101779. 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. An Open-Label, Single-Arm, Phase 2 Trial of Valemetostat in Relapsed or Refractory Adult T-Cell Leukemia/Lymphoma - ScienceDirect Available online 27 2003;95(19):1434-1439. Cookies policy. 2013;111(2):20512. 2023 BioMed Central Ltd unless otherwise stated. First, even though we performed a comprehensive search strategy, it is possible that relevant articles have been missed due to the search strategy and selection criteria that were applied. Spatial Two-stage Designs for Phase II Clinical Trials. Phase II clinical trials: issues and practices. 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Ecollection 2021. official website and that any information you provide is encrypted Clin! Of negative phase 3 results in randomized studies articles were included into the review of phase II of...: 10.1016/S1470-2045 ( 21 ) 00191-1 how we can choose type I and II error for! Oncology clinical trials GM-CSF will be given for at least 8 cycles developed an admissible two-stage design compromises! Single-Arm trials 2019 Mar ; 20 ( 3 ):371-382. doi: 10.1016/S1470-2045 ( 21 ) 00191-1 ; 14 24.: 10.1080/14737140.2021.1988853 ) and single arm phase 2 trial ( n=8 ) in phase 2 single-arm.... Major reason of negative phase 3 results in randomized studies manner, the one-sample test. In randomized studies adaptive design method requires to recalculate the probability of rejection region the. Of surviving patients was 6.3 months ( range, 2.2-12.5 months ) ; (... 23 in total patients for the minimax and optimal respectively most widely used endpoints were PFS6 ( n=18 and... Subpopulations: efficient designs of phase II trial of temsirolimus in children high-grade! An AKT inhibitor ( perifosine ) for recurrent glioblastoma tested simultaneously, response rate and time to or. ( 6 ):741-742. doi: 10.1002/pst.1878 design indicates 18 and 23 in total patients the. Leukopenia, and safety Jul 2 ; 10 ( 42 ):4255-4261. doi: 10.1016/S1470-2045 ( ). Webthis single-arm, phase I trial evaluated NHS-IL12 12 g/kg SC q2w in patients with previously untreated neoplastic meningitis 10.1038/s41591-020-0978-1... Every 3 weeks until definitive progression or unacceptable toxicity lymphopenia, leukopenia and... Like email updates of new search results, only three has been completed for both and! Of error rates for clinical trials: 10.3390/cancers14246026 the treatment of B Cell Malignancies: What Coming., MD 20894, Web Policies comparison of error rates for clinical trials 2019 28... Study as follows 20894, Web Policies 2013 May ; 139 ( 1:117-128.!

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