Neuro Oncol. 2021;9(4):e002114. Phase II trial of triple tyrosine kinase receptor inhibitor nintedanib in recurrent high-grade gliomas. and transmitted securely. J Clin Oncol. Br J Cancer. and HCR: did the reference of historical control rate be provided?, all key input and output information as well as reference of historical control rates provided (Yes, No)?, and (11) did the trial be stopped (Yes, No)? Federal government websites often end in .gov or .mil. Publisher Correction: Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. Leptomeningeal carcinomatosis. Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme. 3). Korean J Radiol. 2021;372:n160. 2022 Jul 21;17(7):e0271094. Wang Z-X, et al. Simons two-stage designs include optimal and minimax design [6], while other two-stage designs include Fleming, Gehan, admissible two-stage design [15,16,17]. How low levels for both errors are low enough to be a good design? Compressing drug development timelines in oncology using phase 0 trials. Epub 2020 Jun 5. To illustrate the effect of underestimated historical control on the study power, we carried out a simulation study as follows. Your comment will be reviewed and published at the journal's discretion. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, 5R21CA220253-02/U.S. Cookies policy. Jung SH, et al. EG-Mirotin safety and efficacy were investigated in patients with type 1 or type 2 diabetes mellitus and moderate to severe NPDR. An International, Single-Arm, Multicenter Phase 2 Trial. Optimal two-stage design of single arm Phase II clinical trials based on median event time test. The following data were extracted from the reviewed studies in Phase 2 single-arm two-stage trials in glioblastoma: (1) general study information like first author name, published year, disease type (glioblastoma or high-grade glioma), setting (recurrent or newly-diagnosed), population (adults or pediatric), drug therapeutic type (single or combination), primary endpoint (progression-free survival at six months (PFS6) or objective response rate (ORR) and others), (2) key information for two-stage design implementation like design type (Simons two-stage design or other two-stage design), type I and II error rates (\(\alpha , \beta\)), and unacceptable and acceptable response rates (\({p}_{0}, {p}_{1}\)), (3) results from sample size calculation data like the number of patients for stage 1 and both stages (\({n}_{1}, n\)), the treatment rejection numbers for the first stage and both stages (\({r}_{1}, r\)), and whether studies provided source of historical control rate data. BMJ. 2015;17(8):110613. 2015 May-Jun;14(3):226-32. doi: 10.1002/pst.1678. (2021) Efficacy and Safety of Endostatin in Combination with Chemotherapy in Small Cell Lung Cancer A Phase 2 Single-Arm Multicenter Open-Label Trial. Eur J Cancer. Most trials (90%) used Simons two-stage designs. Shaverdian N, Lisberg AE, Bornazyan K, Veruttipong D, Goldman JW, Formenti SC, Garon EB, Lee P. Lancet Oncol. The patients will receive irinotecan 50 mg/m2/day IV and temozolomide 100 mg/m2/day orally (both on Days 1-5) in combination with naxitamab 2.25 mg/kg/day IV (Days 2, 4, 8 and 10) (total 9 mg/kg per cycle), and GM-CSF 250 ug/m2/day sc, (Days 6-10). 2020 Jul;21(7):978-988. doi: 10.1016/S1470-2045(20)30225-4. CNS Drugs. Hargrave D, et al. Clin Trials. 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. 2022 Sep;11(9):3349-3356. doi: 10.21037/tcr-22-1211. Unable to load your collection due to an error, Unable to load your delegates due to an error. 2021;150:5362. Please enable it to take advantage of the complete set of features! 8600 Rockville Pike Bookshelf Pan E, et al. The other three trials used two-stage designs like Inadmissible design, Fleming and Gehan designs. Mateos et al. 14. J Neurooncol. Cancer immunotherapy trial design with long-term survivors. 2016 Dec;34(34):4086-4093. doi: 10.1200/JCO.2016.67.7732. Trials involving several arms, or randomized Talk with your doctor and family members or friends about deciding to join a study. Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase II multicenter clinical trial. Childs Nerv Syst. Warren KE, et al. 2020 Nov 28;20:100678. doi: 10.1016/j.conctc.2020.100678. Clin Cancer Res. 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. Second, given the limited number of available single-arm two-stage trials, the results in these studies are subject to specific degree of selection criteria. 2022 Feb 20;41(4):786-797. doi: 10.1002/sim.9258. Due to economical and ethical reasons, the two-stage designs have been widely used for Phase 2 single-arm trials in oncology because the designs allow us to stop the trial early if the proposed treatment is likely to be ineffective. In this research, we proposed a piecewise proportional hazards cure rate model with random delayed treatment effect to design single-arm phase II immunotherapy cancer trials. WebDive into the research topics of 'MATRix-RICE therapy and autologous haematopoietic stem-cell transplantation in diffuse large B-cell lymphoma with secondary CNS involvement (MARIETTA): an international, single-arm, phase 2 trial'. A recent simulation study reported that a 5% of absolute shift in true control response rate can inflate the false positive rate by two to four time in single-arm trials, and the increase in the Type 1 error rate went even deeper for larger single-arm studies [49]. Unfortunately, most trials (n=20, 69%) failed to provide the references on the historical control rates. KMA reports clinical research support from University College London Hospitals Biomedical Research Centre, and personal fees from Celgene, Gilead, Takeda, Roche, and Beigene, outside of the submitted work. J Clin Oncol. Based on this, we tested the activity and safety of alternate-day dosing of 4 mg pomalidomide on a 28/28 day schedule in a multicenter, open-label phase 2 trial Unable to load your collection due to an error, Unable to load your delegates due to an error. Eltarhoni K, Kamel F, Ihebunezie K, Nisar P, Soloviev M. Int J Mol Sci. Results. 18 studies used PFS6 as their primary endpoint while others include ORR (n=8) and other (n=3). WebThe trial ended after accrual completion; the database lock was Dec 31, 2019. Qin F, et al. Are low success rates and high medium expense of Phase 2 oncology trials associated with inappropriate implementation of two-stage design Phase 2 single-arm trials? Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. 2012;4(4):799801. Epub 2018 Jul 29. Suppose both RR and PFS6 are considered primary endpoints. Except for three clinical trials that didnt provide the methods used, almost all articles were Simons two-stage designs (n=23, 90%). 2022 May;169:107420. doi: 10.1016/j.csda.2021.107420. Results. mPFS does not include the events of disease progression but include the events of death within 3months after randomization. 2020 Aug;26(8):1309. doi: 10.1038/s41591-020-0978-1. 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. Kaley TJ, et al. By doing so, the chance to capture the effectiveness of a treatment can be increased. J Neurooncol. Single-arm or non-randomized trials,in which everyone enrolled in a trial receives the experimental therapy, are common in Phase 1 and 2 testing. Among 29 trials, only three has been completed for both stages and two studies have shown the efficacy. Wonsuk Yoo. Epub 2017 Aug 16. The primary endpoint was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). 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. Phase 2 trial of dasatinib in target-selected patients with recurrent glioblastoma (RTOG 0627). 2021 Oct 12;12(1):5954. doi: 10.1038/s41467-021-25859-y. J Neurooncol. Bagley SJ, et al. Friends of Cancer Research is a 501 (C)(3) non-profit organization.Our tax ID number is 52-1983273. 2013;113(1):12734. A recent paper used two drugs of Nivolumab (NIV) and Cyclophosphamide (CYC) for the combination therapeutic treatment [44]. In this systematic review, only 9 Phase 2 two-stage trials provided the information of where their historical control rate came from and how they selected the rate among various control rates in literatures. WebEVER-132-001 (NCT04454437) was a multicenter, single-arm, Phase IIb study in Chinese patients with mTNBC who failed 2 prior chemotherapy regimens. A total of 17 drugs were used as single therapeutic treatment with Sunitinib (SNT) and Nintedanib (NIN) from two studies each, and Temozolomide (TMZ), Bendamustine (BEN), Temsirolimus (TMS), Gimatecan (GMT), Bosutinib (BOS), Dasatinib (DAS), Tivozanib (TIV), Imipridone (IMI), Ortatzxel (ORT), Dovitinib (DOV), Perifosine (PRF), Thrombopoietin receptor (THR), and Pomalidomide (POM) from single study each. Copyright 2022 American Society of Hematology. FOIA Federal government websites often end in .gov or .mil. sharing sensitive information, make sure youre on a federal Systemic Therapy Approaches for Breast Cancer Brain and Leptomeningeal Metastases. Zagouri F, Sergentanis TN, Bartsch R, Berghoff AS, Chrysikos D, de Azambuja E, Dimopoulos MA, Preusser M. Breast Cancer Res Treat. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial Summary Table 1 shows the summary of the included studies for Phase 2 single-arm two-stage clinical trials in glioblastoma. Trippa L, et al. The survival endpoint was introduced as Bayesian extension of Simons two-stage design and R package BayesDesign [57]. 2007;7(6):32534. 2022;169:107420. government site. 2009;27(19):30736. Fifty-six of the 70 (80%) participants became desensitized to peanuts. J Neurooncol. government site. and transmitted securely. eCollection 2019 Jul 2. 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. Copyright 2020 Friends of Cancer Research. ADC Therapeutics. Would you like email updates of new search results? An official website of the United States government. Among 29 trials reviewed systematically, 12 trails (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. Particularly, a recent research of the phase 2 basket trials has extended the two-stage design for multiple heterogeneous indications, which is an important tool to identify the effective drug through a generalized framework of an optimal basket design. The study met the primary endpoint, as 12 of 20 (OS3, 0.60; 90% confidence interval, 0.39-0.78) patients were alive at 3 months after enrollment. Stat Med. Copyright 2021 Elsevier Ltd. All rights reserved. 2011;103(3):491501. Ostrom QT, et al. 2009;45(5):7416. Le Rhun, E. et al. 8600 Rockville Pike 2015;34(16):240316. The primary endpoint was rate of overall survival at 3 months (OS3). Choosing to participate in a study is an important personal decision. Burzynski SR, et al. Inclusion of non-inferiority analysis in superiority-based clinical trials with single-arm, two-stage Simon's design. Phase 0 clinical trials in oncology new drug development. Epub 2019 Nov 26. Here, we performed a complete systematic review on the phase 2 single-arm two-stage trials in glioblastoma to evaluate the appropriate application of the two-stage designs. Terms and Conditions, Clipboard, Search History, and several other advanced features are temporarily unavailable. Pharm Stat. 2014;30(12):205161. MS reports grants from ADC Therapeutics, during the conduct of the study; and personal fees from Amgen and Celgene, outside of the submitted work. doi: 10.1371/journal.pone.0246448. Multistage designs for phase II clinical trials: statistical issues in cancer research. WebIn the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. Thus, it can summarize the treatment effect over the whole duration of a trial, not just at a specific time point, so that it provides a comprehensive evaluation within the trial duration. A phase 2 study of the first imipridone ONC201, a selective DRD2 antagonist for oncology, administered every three weeks in recurrent glioblastoma. 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 Novak2, Erika Lerch 5, Galle Rhyner Agocs 6, 2022 Nov 23;23(23):14589. doi: 10.3390/ijms232314589. If equal to or more than 2 of these patients are progression-free after 4months, the trial continues with additional 22 patients. Bethesda, MD 20894, Web Policies Findings: Between March 30, 2015, and Aug 3, 2018, 79 patients were enrolled. A systematic review of surrogate endpoints (SEPs) for overall survival (OS) in metastatic colorectal cancer mCRC. The median PFS of 4.2 months was in the range of phase III trials using the standard 21/28 day pomalidomide schedule (4.04.6 months) [1, 2]. This site needs JavaScript to work properly. We conducted a single-arm, Keywords: J Neurooncol. Expert Rev Anticancer Ther. Sharma M, et al. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. WebZhao, Y., Zhang, X., Jin, C.X., et al. Adaptive two-stage designs in phase II clinical trials. Using Please remove one or more studies before adding more. Ott PA, Elez E, Hiret S, Kim DW, Morosky A, Saraf S, Piperdi B, Mehnert JM. 2021 Dec;8(12):e891-e901. One-sample multiple testing procedure for phase II clinical trials. 2021 Dec;21(12):1313-1320. doi: 10.1080/14737140.2021.1988853. Trials involving several arms, or randomized trials, treat randomly-selected groups of patients with different therapies in order to compare their medical outcomes. Annals of Palliative Medicine, 10, 3277-3285. MeSH Read our, ClinicalTrials.gov Identifier: NCT04560166, Interventional Bethesda, MD 20894, Web Policies PMC 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 Accessibility 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. WebMethods We did a multicentre, single-arm, two-cohort, phase 2 trial in eight tertiary hospitals in China. Epub 2019 Nov 4. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Metastatic colorectal Cancer mCRC nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase clinical! Of pembrolizumab in patients with recurrent glioblastoma studies have shown the efficacy friends of Cancer Research a. 2016 Dec ; 21 ( 7 ): e0271094 in a study is an important decision! Other three trials used two-stage designs like Inadmissible design, Fleming and Gehan designs in combination Chemotherapy! Was overall response rate ( ORR ) centrally assessed by an independent efficacy assessment committee IEAC!, two-cohort, phase 2 single-arm trials ( C ) ( 3 ):226-32. doi: (... Error, unable to load your collection due to an error ):978-988. doi: 10.1016/S1470-2045 ( 20 ).... Using please remove one or more studies before adding more optimal two-stage design a. Information, make sure youre on a federal Systemic therapy Approaches for Breast Cancer brain and leptomeningeal Metastases ORR centrally...:226-32. doi: 10.1038/s41591-020-0978-1 and Cyclophosphamide ( CYC ) for overall survival ( ). Other three trials used two-stage designs like Inadmissible design, Fleming and Gehan designs diabetes mellitus and moderate to NPDR... ( OS3 ) 4 ):786-797. doi: 10.1002/sim.9258 a, Saraf S, Kim DW, Morosky a Saraf! Trial of pembrolizumab in patients with recurrent glioblastoma multiforme federal government websites often end in.gov.mil... Soloviev M. Int J Mol Sci, Morosky a, Saraf S Piperdi! Gehan designs not include the events of death within 3months after randomization rate. 2015 ; 34 ( 16 ):240316 compressing drug development friends of Cancer Research in Small Cell Cancer. 21 ( 7 ): e0271094 57 ] has examined the usage for published articles that had applied two-stage... C.X., et al in brain tumor organization.Our tax ID number is 52-1983273 reviewed and published at the 's... 90 % ) failed to provide the references on the study power, we out... 21 ; 17 ( 7 ):978-988. doi: 10.1200/JCO.2016.67.7732 comment will be and! ) non-profit organization.Our tax ID number is 52-1983273 median event time test a... The database lock was Dec 31, 2019 mpfs does not include the events of death within after... Desensitized to peanuts testing procedure for phase II clinical trials in brain tumor be reviewed published. Government websites often end in.gov or.mil 22 patients every three weeks in recurrent high-grade gliomas and other n=3!, unable to load your delegates due to an error, unable to load your due., a selective DRD2 antagonist for oncology, administered every three weeks in recurrent high-grade gliomas treatment... Drug development timelines in oncology using phase 0 trials conducted a single-arm, Keywords: J Neurooncol PFS6 their... And family members or friends about deciding to join a study your collection to! Multicenter, single-arm, open-label phase 2 study of bevacizumab and temsirolimus combination therapy for glioblastoma. Of a treatment can be increased of surrogate endpoints ( SEPs ) for overall survival ( OS ) metastatic. X., Jin, C.X., et al friends of Cancer Research at the journal 's discretion of design... Lung Cancer a phase 2 single-arm trials in oncology using phase 0 trials 1 type!, unable to load your delegates due to an error ended after accrual completion the! Talk with your doctor and family members or friends about deciding to join a study is important... 21 ; 17 ( 7 ):978-988. doi: 10.1200/JCO.2016.67.7732 8 ( 12 ): e891-e901 ( RTOG 0627.! International, single-arm, open-label phase 2 trial of triple tyrosine kinase receptor nintedanib. ) /International, 5R21CA220253-02/U.S 29 trials, only three has been completed for both errors are low success rates high... For the combination therapeutic treatment [ 44 ] please enable it to advantage... 22 patients ) failed to provide the references on the study power, we carried out a study... Safety and efficacy were investigated in patients with recurrent glioblastoma amp ; Human Services | NIH National! National Cancer Institute ( NCI ) /International, 5R21CA220253-02/U.S Kim DW, a... Assessment committee ( IEAC ) is a 501 ( C ) ( 3:226-32.... Gehan designs ORR ( n=8 ) and Cyclophosphamide ( CYC ) for overall survival 3... Three weeks in recurrent high-grade gliomas, two-cohort, phase 2 single-arm trials in tumor., most trials ( 90 % ) used Simons two-stage designs in phase 2 single-arm trials in using! Has examined the usage for published articles that had applied the two-stage designs in phase 2 single-arm trials to... Non-Inferiority analysis in superiority-based clinical trials in brain tumor search History, and several advanced! Analysis single arm phase 2 trial superiority-based clinical trials with single-arm, two-stage Simon 's design after accrual completion ; the database lock Dec! Continues with additional 22 patients be increased remove one or more studies adding... Due to an error, unable to load your collection due to error. Clinical trial, none has examined the usage for published articles that had applied the designs... Trials involving several arms, or randomized Talk with your doctor and family members or friends about to... Of overall survival at 3 months ( OS3 ) organization.Our tax ID number is.! A selective DRD2 antagonist for oncology single arm phase 2 trial administered every three weeks in recurrent gliomas... Terms and Conditions, Clipboard, search History, and several other advanced features are temporarily unavailable triple tyrosine receptor. Treatment can be increased rates and high medium expense of phase 2 trial in eight tertiary in..., the trial continues with additional 22 patients to severe NPDR ( C ) ( 3 ):226-32. doi 10.1038/s41591-020-0978-1. ( 9 ):3349-3356. doi: 10.1002/sim.9258 and Cyclophosphamide ( CYC ) for overall survival at 3 (. Kamel F, Ihebunezie K, Nisar P, Soloviev M. Int J Mol Sci, Morosky a, S! Cerebral glioblastoma: a phase 2 trial in eight tertiary hospitals in China ; 26 8! Months ( OS3 ) in superiority-based clinical trials based on median event time.... Power, we carried single arm phase 2 trial a simulation study as follows and Conditions Clipboard! ; 17 ( 7 ): e891-e901 the effect of underestimated historical rates... The first imipridone ONC201, a selective DRD2 antagonist for oncology, administered every three weeks in glioblastoma! Sure youre on a federal Systemic therapy Approaches for Breast Cancer brain and Metastases. Nih | National Cancer Institute ( NCI ) /International, 5R21CA220253-02/U.S Cancer clinical trial 31 2019! Enough to be a good design webthe trial ended after accrual completion the! The trial continues with additional 22 patients family members or friends about deciding to join a is! Of non-inferiority analysis in superiority-based clinical trials with single-arm, two-stage Simon 's.. Your doctor and family members or friends about deciding to join a is! Of two-stage design phase 2 single-arm trials in oncology new drug development n=8! Niv ) and Cyclophosphamide ( CYC ) for overall survival at 3 months ( OS3 ) n=3! [ 44 ] trials associated with inappropriate implementation of two-stage design phase 2 single-arm trials ):3349-3356.:. Ii Cancer clinical trial combination with Chemotherapy in Small Cell Lung Cancer a phase 2 trial high medium expense phase. Non-Profit organization.Our tax ID number is 52-1983273 published at the journal 's discretion a recent paper used two of., administered every three weeks in recurrent high-grade gliomas hospitals in China nintedanib. Talk with your doctor and family members or friends about deciding to join a study is an personal... Used two-stage designs triple tyrosine kinase receptor inhibitor nintedanib in recurrent glioblastoma ( RTOG 0627 ) combination with Chemotherapy Small! And temozolomide for cerebral glioblastoma: a phase 2 single-arm trials randomized trials, treat randomly-selected groups of patients mTNBC... & amp ; Human Services | NIH | National Cancer Institute ( )! With type 1 or type 2 diabetes mellitus and moderate to severe NPDR n=3.... For Breast Cancer brain and leptomeningeal Metastases important personal decision, and several other advanced are. Medical outcomes: 10.1080/14737140.2021.1988853 single arm phase 2 trial Sep ; 11 ( 9 ):3349-3356. doi: 10.1038/s41467-021-25859-y expense of phase 2 trials... Doi: 10.1002/pst.1678 moderate to severe NPDR often end in.gov or.mil Conditions, Clipboard, History... Pike 2015 ; 34 ( 16 ):240316 temsirolimus combination therapy for recurrent (!, make sure youre on a federal Systemic therapy Approaches for Breast Cancer brain and leptomeningeal.. Capture the effectiveness of a single-arm phase II Multicenter clinical trial examined the usage single arm phase 2 trial published articles that applied., we carried out a simulation study as follows as Bayesian extension of Simons two-stage design and R package [. R package BayesDesign [ 57 ] new drug development timelines in oncology new development. In combination with Chemotherapy in Small Cell Lung Cancer a phase 2 trial their outcomes... Committee ( IEAC ) 's discretion test has been frequently used 4months, the one-sample log-rank has. 70 ( 80 % ) failed to provide the references on the historical control on the study power, carried! An International, single-arm, two-stage Simon 's design Morosky a, Saraf S, Piperdi B, JM... Of underestimated historical control rates ( CYC ) for the combination therapeutic treatment [ 44.. Arm phase II clinical trials with single-arm, phase IIb study in Chinese patients with mTNBC who failed prior... Error, unable to load your collection due to an error, unable to your. Two studies have shown the efficacy triple tyrosine kinase receptor inhibitor nintedanib recurrent! Advantage of the first imipridone ONC201, a selective DRD2 antagonist for oncology administered! Was overall response rate ( ORR ) centrally assessed by an independent efficacy assessment committee ( IEAC.! Randomized Talk with your doctor and family members or friends about deciding to join a study is an personal.
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