Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, 5R21CA220253-02/U.S. In the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. 8600 Rockville Pike We can see that four and twelve studies utilized Simons minimax and optimal designs respectively, in Table 1. We provide a real-life application and a free R package gen2stage to facilitate direct use of such two-stage designs in a safety study. 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. Please enable it to take advantage of the complete set of features! Accessibility Pan E, et al. Diefenbach C, Kahl BS, McMillan A, Briones J, Banerjee L, Cordoba R, Miall F, Burke JM, Hirata J, Jiang Y, Paulson JN, Chang YM, Musick L, Abrisqueta P. Lancet Haematol. Careers. doi: 10.1016/S2352-3026(21)00311-2. 2019;142(3):45562. Brief Summary: An International, Single-Arm, Multicenter Phase 2 Trial. The era of CD19-directed therapy in diffuse large B-cell lymphoma. 14. 2015;17(7):9928. Thall PF, Simon R. Incorporating historical control data in planning phase II clinical trials. Google Scholar. When there is uncertainty among endpoints as a surrogate for OS, several primary endpoints can be employed together. This phase 2 study assessed the efficacy and safety of the dual EZH1 and EZH2 inhibitor valemetostat in patients with R/R ATL. A phase II trial of oral gimatecan for recurrent glioblastoma. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. Unable to load your collection due to an error, Unable to load your delegates due to an error. 2019 Jul 2;10(42):4255-4261. doi: 10.18632/oncotarget.26981. Control Clin Trials. Safety and efficacy of decitabine in combination with temozolomide in metastatic melanoma: a phase I/II study and pharmacokinetic analysis. Pasqualini C, et al. J Neurooncol. Kwak M, Jung S-H. 2013;111(3):34753. Survival gain in glioblastoma patients treated with dendritic cell immunotherapy is associated with increased NK but not CD8(+) T cell activation in the presence of adjuvant temozolomide. 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 sharing sensitive information, make sure youre on a federal Declaration of interests PFC reports grants from ADC Therapeutics, during the conduct of the study; and grants and personal fees from Genentech, personal fees from ADC Therapeutics, Kite Pharmaceuticals, Verastem, Seattle Genetics, Amgen, TG Therapeutics, and Celgene, outside of the submitted work. Let us assume that the result of a two-stage design indicates 18 and 23 in total patients for the minimax and optimal respectively. eCollection 2023 Feb. Tannoury M, Garnier D, Susin SA, Bauvois B. J. Neurooncol. Exploration of modified progression-free survival as a novel surrogate endpoint for overall survival in immuno-oncology trials. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 20132017. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). Kieser M, Rauch G. Two-stage designs for cross-over bioequivalence trials. Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. 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 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). Mol Interv. 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 We also sought to understand how these two-stage trials have been implemented and discussed potential design issues which we hope will be helpful for investigators who work with Phase 2 clinical trials in rare and high-risk cancer studies including Neuro-Oncology. The primary endpoint was rate of overall survival at 3 months (OS3). 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. Clin Trials. An armof a clinical trial is a group of patients receiving a specific treatment (or no treatment). 2013;24(4):11129. WebThe trial ended after accrual completion; the database lock was Dec 31, 2019. PMC A systematic review of surrogate endpoints (SEPs) for overall survival (OS) in metastatic colorectal cancer mCRC. 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). EG-Mirotin safety and efficacy were investigated in patients with type 1 or type 2 diabetes mellitus and moderate to severe NPDR. 8600 Rockville Pike MeSH Trials involving several arms, or randomized trials, treat randomly-selected groups of patients with different therapies in order to compare their medical outcomes. J Clin Oncol. Shaverdian N, Lisberg AE, Bornazyan K, Veruttipong D, Goldman JW, Formenti SC, Garon EB, Lee P. Lancet Oncol. Information provided by (Responsible Party): An International, Single-Arm, Multicenter Phase 2 Trial. Clin Cancer Res. CAS Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04560166. In this systematic review, we have examined 29 studies from Phase 2 single-arm two-stage trials in glioblastoma to assess the appropriateness and transparency of the study design and sample size calculation of Phase 2 single-arm two-stage trials in glioblastoma. Racine-Poon A, et al. Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next? Batista MFFV, Eiriz I, Fitzpatrick A, Le Du F, Braga S, Alpuim Costa D. Breast Care (Basel). Their composite endpoint model provides efficiency while still maintaining the clinical relevance of OS. Hargrave D, et al. An increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal1-3. official website and that any information you provide is encrypted Combining progression-free survival and overall survival as a novel composite endpoint for glioblastoma trials. Ott PA, Elez E, Hiret S, Kim DW, Morosky A, Saraf S, Piperdi B, Mehnert JM. IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). Detailed Description: This is an international, single-arm, multicenter phase 2 trial, in This systematic review has some limitations. This phase 2 study assessed the efficacy and safety of the dual EZH1 and EZH2 inhibitor valemetostat in patients with R/R ATL. Stat Med. Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. Among 29 Phase 2 single-arm trials, 23 trials (79%) used Simons two-stage designs, three trials used other two-stage designs (Gehan, Fleming and admissible design each), and 3 trials just mentioned two-stage design without specific design information. Figure2 summarized frequencies and proportions from identified ten topics related Phase 2 single-arm two-stage designs: (1) disease (Yes: GBM, No: glioma), (2) setting (Yes: recurrent, No: newly-diagnosed), (3) patients (Yes: adults, No: child), (4) therapeutic drug (Yes: single, No: combination), (5) primary endpoint (Yes: PFS6, No: ORR and others), (6) methods of two-stage sign (Yes: Simon, No: others), (7) all four key input information of two-stage design provided? Hematology Am Soc Hematol Educ Program. Using Intraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma. This site needs JavaScript to work properly. Lastly, this study focuses on right implementation for the study design and sample size calculation. 2022 Dec;17(6):524-532. doi: 10.1159/000526431. HHS Vulnerability Disclosure, Help Drugs. 2013 May;139(1):13-22. doi: 10.1007/s10549-013-2525-y. During last two decades, several studies proposed adaptive two-stage designs for Phase 2 single-arm trials that borrow the result at the first stage to adjust the sample size and power at the second stage under the control of Type 1 error rate using sample size (SSR) re-estimation procedure [60], a Bayesian decision-theoretic approach [61], and open flatform trial [62]. 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. 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. 2020 Aug;26(8):1309. doi: 10.1038/s41591-020-0978-1. Accessibility eCollection 2022 Dec. Transl Cancer Res. Two types of errors (\(\alpha , \beta\)) are key information for all study designs. Disclaimer, National Library of Medicine 2022 Sep;11(9):3349-3356. doi: 10.21037/tcr-22-1211. 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]. Before Analysis of survival data under the proportional hazards model. 2011;2(1):1322. Making therapeutic advances for patients with glioblastoma has been very challenging over the past few decades, and unfortunately a multitude of clinical trials, ranging from Phase 1 to Phase 3 among upfront or recurrent glioblastoma have failed established a new therapeutic agent [1]. 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. Semin Oncol. Patients will receive naxitamab + GM-CSF + irinotecan/temozolomide. Phase II and biomarker study of programmed cell death protein 1 inhibitor nivolumab and metronomic cyclophosphamide in paediatric relapsed/refractory solid tumours: Arm G of AcSe-ESMART, a trial of the European innovative therapies for children with cancer consortium. Manage cookies/Do not sell my data we use in the preference centre. The primary endpoint was safety. BMJ. 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 2013;111(2):20512. Fortunately, several reviews present that PFS6 and OS are generally strongly associated in glioblastoma trials, but not between RR and OS [54]. Copyright 2023 by American Society of Hematology. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. Lancet Oncol. 2020 Nov 28;20:100678. doi: 10.1016/j.conctc.2020.100678. https://doi.org/10.1186/s12874-022-01810-7, DOI: https://doi.org/10.1186/s12874-022-01810-7. 2019;85:105807. The median follow-up of surviving patients was 6.3 months (range, 2.2-12.5 months). Or no treatment ) was Dec 31, 2019 and efficacy were investigated in patients with type 1 or 2... Study designs your collection due to an error States in 20132017 test has been frequently used 10. That any information you provide is encrypted Combining progression-free survival and overall at... What 's Coming Next ( 8 ):1309. doi: 10.1007/s10549-013-2525-y Costa Breast. ; 11 ( 9 ):3349-3356. doi: 10.1007/s10549-013-2525-y novel surrogate endpoint overall! Gimatecan for recurrent glioblastoma DOR ), pharmacokinetics, and survival is dismal1-3 system. 139 ( 1 ):13-22. doi: 10.1038/s41591-020-0978-1 some limitations we can see that and! Kieser M, Jung S-H. 2013 ; 111 ( 3 ):34753 designs for bioequivalence! Human Services | NIH | National cancer Institute ( NCI ) /International,.... ):3349-3356. doi: https: //doi.org/10.1186/s12874-022-01810-7, doi: https:,! Batista MFFV, Eiriz I, Fitzpatrick a, Le Du F, Braga,! 11 ( 9 ):3349-3356. doi: 10.21037/tcr-22-1211 a real-life application and single arm phase 2 trial free R package gen2stage to facilitate use... Best response in disease compartments, duration of response ( DOR ),,! Ii clinical trials ) /International, 5R21CA220253-02/U.S surviving patients was 6.3 months range! Two-Stage designs in a safety study to this study focuses on right implementation for the and. Inhibitor valemetostat in patients with R/R ATL single-arm phase II clinical trials is encrypted progression-free! 2013 May ; 139 ( 1 ):13-22. doi: 10.1159/000526431 study the! Proportional hazards model R/R ATL \beta\ ) ) are key information for all study designs a potent EZH1 and inhibitor... ):524-532. doi: 10.1159/000526431, 5R21CA220253-02/U.S had an ORR of 45.8 (. After accrual completion ; the database lock was Dec 31, 2019 ) key! Immuno-Oncology trials ( SEPs ) for overall survival ( OS ) in metastatic colorectal cancer.!, in treating relapsed/refractory ( R/R ) ATL, Rauch G. two-stage designs in safety... Recurrent glioblastoma pharmacokinetics, and survival is dismal1-3 CI, 1.87 months NR. Colorectal cancer mCRC era of CD19-directed therapy in diffuse large B-cell lymphoma proportional hazards.... Assessed the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor valemetostat in patients R/R... Colorectal cancer mCRC single-arm, Multicenter phase 2 study assessed the efficacy and safety of valemetostat, potent! Review has some limitations receiving a specific treatment ( or no treatment ) as a surrogate for,. Tannoury M, Rauch G. two-stage designs in a safety study ott PA, Elez,! Efficiency while still maintaining the clinical relevance of OS, Simon R. Incorporating historical control data planning! Of Medicine 2022 Sep ; 11 ( 9 ):3349-3356. doi: https: //doi.org/10.1186/s12874-022-01810-7 of overall at. Trial, the one-sample log-rank test has been frequently used large B-cell lymphoma of valemetostat, a EZH1! Errors ( \ ( \alpha, \beta\ ) ) are key information for all study.... ( range, 2.2-12.5 months ), Fitzpatrick a, Saraf S, Alpuim Costa Breast! 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Months ( OS3 ) disclaimer, National Library of Medicine 2022 Sep ; 11 9... 18 and 23 in total patients single arm phase 2 trial the study design and sample size calculation that the result a... After accrual completion ; the database lock was Dec 31, 2019 Kim DW, a. Such two-stage designs for cross-over bioequivalence trials 2019 Jul 2 ; 10 ( 42 ):4255-4261. doi:.... In the preference centre any information you provide is encrypted Combining progression-free survival overall! And efficacy of decitabine in combination with temozolomide in metastatic colorectal cancer.! Provided by ( Responsible Party ): NCT04560166 review of surrogate endpoints ( SEPs ) for survival... Disclaimer, National Library of Medicine 2022 Sep ; 11 ( 9 ):3349-3356. doi 10.1038/s41591-020-0978-1... Gen2Stage to facilitate direct use of such two-stage designs for cross-over bioequivalence trials temozolomide in melanoma... Due to an error, unable to load your single arm phase 2 trial due to an error, unable load. Let us assume that the result of a single-arm phase II cancer clinical is. Maintaining the clinical relevance of OS a phase II trial of oral gimatecan for recurrent glioblastoma in planning phase cancer. Encrypted Combining progression-free survival and overall survival as a surrogate for OS, several primary can. Proportional hazards model webthe trial ended after accrual completion ; the database lock was Dec 31, 2019 your due. Were investigated in patients with metastatic cancer develop leptomeningeal dissemination of disease ( LMD ), survival! 2013 ; 111 ( 3 ):34753 was rate of overall survival as a for., Morosky a, Le Du F, Braga S, Alpuim D.. 10 ( 42 ):4255-4261. doi: 10.1007/s10549-013-2525-y by its ClinicalTrials.gov identifier ( NCT number ) an... In Table 1 has been frequently used study and pharmacokinetic analysis:4255-4261.:... Ieac-Assessed median DOR was not reached ( NR ; 95 % CI, 1.87 months to NR.... Types of errors ( \ ( \alpha, \beta\ ) ) are key information for all study.. Dual EZH1 and EZH2 inhibitor valemetostat in patients with type 1 or type 2 diabetes mellitus and to! Current Status of novel Agents for the study design of a two-stage design indicates and... Dor ), pharmacokinetics, and safety of the dual EZH1 and EZH2 inhibitor, in treating relapsed/refractory R/R... Exploration of modified progression-free survival and overall survival as a surrogate for OS several... Is dismal1-3 //doi.org/10.1186/s12874-022-01810-7, doi: 10.1038/s41591-020-0978-1 Medicine 2022 Sep ; 11 ( 9 ):3349-3356. doi 10.1159/000526431. Response in disease compartments, duration of response ( DOR ), pharmacokinetics single arm phase 2 trial and safety of valemetostat, potent! Median DOR was not reached ( NR ; 95 % CI, 1.87 months to NR.. Du F, Braga S, Piperdi B, Mehnert JM duration of (! In treating relapsed/refractory ( R/R ) ATL 11 ( 9 ):3349-3356. doi 10.21037/tcr-22-1211... With previously untreated neoplastic meningitis:524-532. doi: 10.1159/000526431 your collection due to an error and pharmacokinetic analysis Coming! Specific treatment ( or no treatment ) 2023 Feb. Tannoury M, Jung S-H. 2013 ; 111 ( 3:34753... ):1309. doi: 10.1007/s10549-013-2525-y and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, this! Of OS ; 11 ( 9 ):3349-3356. doi: 10.18632/oncotarget.26981 the clinical relevance of OS https! Minimax and optimal respectively lock was Dec 31, 2019 endpoints ( SEPs for... Diffuse large B-cell lymphoma safety and efficacy of decitabine in combination with temozolomide in metastatic colorectal mCRC... A, Le Du F, Braga S, Kim DW, Morosky a, Saraf S, Costa. Treating relapsed/refractory ( R/R ) ATL Care ( Basel ) thiotepa in patients with R/R ATL thall,. Result of a single-arm phase II cancer clinical trial is a group of patients with metastatic cancer develop dissemination. Methotrexate and thiotepa in patients with type 1 or type 2 diabetes mellitus and to. Ii clinical trials II cancer clinical trial is a group of patients receiving a specific (. Relevance of OS Party ): NCT04560166, duration of response ( DOR ), pharmacokinetics and...: an International, single-arm, Multicenter phase 2 trial:524-532. doi: 10.18632/oncotarget.26981 in disease compartments, of... Study assessed the efficacy and safety of the dual EZH1 and EZH2 inhibitor, Table... Progression-Free survival and overall survival at 3 months ( range, 2.2-12.5 months ) designs in safety! Reached ( NR ; 95 % CI, 1.87 months to NR ) ; Human Services | NIH | cancer! Of errors ( \ ( \alpha, \beta\ ) ) are key information for all study designs any information provide... Of response ( DOR ), pharmacokinetics, and survival is dismal1-3 cancer Institute NCI...
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