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Before This implies that most brain tumor clinical trials are at high risk with great uncertainty in trial outcomes. WebThis multicenter phase 2 trial (NCT04102150; https://clinicaltrials.gov/ct2/show/NCT04102150; DS3201-A-J201) enrolled patients with J Neurooncol. Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase II multicenter clinical trial. The .gov means its official. The https:// ensures that you are connecting to the 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. Their composite endpoint model provides efficiency while still maintaining the clinical relevance of OS. PMC WY, SK, and MG wrote the main manuscript text and WY and SK prepared Table 1 and Figs. The discrete conditional error based adaptive design method requires to recalculate the probability of rejection region using the results from the first stage. 11, 561569 (1993). FOIA A phase 2 study of the first imipridone ONC201, a selective DRD2 antagonist for oncology, administered every three weeks in recurrent glioblastoma. 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. Epub 2020 Jun 5. Neuro Oncol. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). Stat Med. Anticancer Res. First, if expected sample size of minimax design is close to that of optimal design, the minimax design might be a good option over the optimal design. 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. California Privacy Statement, J Cancer. 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. Methods TOCIVID-19 is an academic multicenter, single-arm, open-label, phase 2 study. Lastly, this study focuses on right implementation for the study design and sample size calculation. Two types of errors (\(\alpha , \beta\)) are key information for all study designs. J Neurooncol. 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. Epub 2021 May 11. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, 5R21CA220253-02/U.S. Le Rhun E, Devos P, Houillier C, Cartalat S, Chinot O, Di Stefano AL, Lepage C, Reyns N, Dubois F, Weller M. Romiplostim for temozolomide-induced thrombocytopenia in glioblastoma: The PLATUM trial. The most widely used endpoints were PFS6 (n=18) and ORR (n=8) in Phase 2 single-arm trials. 2023 BioMed Central Ltd unless otherwise stated. in Central Nervous System Metastasis, the Biological Basis and Clinical Consideraiton (ed. An Open-Label, Single-Arm, Phase 2 Trial of Valemetostat in Relapsed or Refractory Adult T-Cell Leukemia/Lymphoma - ScienceDirect Available online 27 A prospective phase II single-institution trial of sunitinib for recurrent malignant glioma. In the classical approach, further 22 patients should be recruited for the second stage although only 3 (13.6%) further patients without progression after 4months are required to demonstrate efficacy. The .gov means its official. 2011;105(3):52330. 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]. A Phase 2 single-arm study using two-stage design [42], where a new treatment option of hypoxia activated evofosfamide (TH302) for patient with recurrent bevacizumab-refractory glioblastoma was investigated. Furthermore, a couple of trials did not provide explanation and description about the results of sample size calculation (no shown here). 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 Careers. If it may be available to enroll only ten patients per year, the optimal design needs a half year longer than the minimax design. By doing so, the chance to capture the effectiveness of a treatment can be increased. Jung et al. Valemetostat 200 mg orally once daily demonstrated promising efficacy and manageable toxicity in heavily pretreated patients. Zhou H, et al. 2019 Dec 1;25(23):6986-6994. doi: 10.1158/1078-0432.CCR-19-0711. Simon R, et al. sharing sensitive information, make sure youre on a federal Due to the insufficient study participants, incurability status with heterogeneity nature, and ethical reasons, the single-arm trials in glioblastoma and CNS cancers are generally performed with the two-stage designs to allow early stopping for futility. Taylor JW, et al. Phase II clinical trials: issues and practices. Cancers (Basel). WebAn increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal 1-3. A systematic review of surrogate endpoints (SEPs) for overall survival (OS) in metastatic colorectal cancer mCRC. Eur J Cancer. Neurosurg. Bookshelf 2022 Nov 23;23(23):14589. doi: 10.3390/ijms232314589. Int Stat Rev/Revue Int de Stat. Childs Nerv Syst. Eastern Cooperative Oncology Group. Stat Med. GBM: glioblastoma, PFS6: progression-free survival at 6months, Key info: key input parameters for two-stage design, Right SS: did two-stage sample size calculation be appropriately implanted? MS reports grants from ADC Therapeutics, during the conduct of the study; and personal fees from Amgen and Celgene, outside of the submitted work. 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]. BSK reports grants from ADC Therapeutics, during the conduct of the study; and personal fees from Seattle Genetics and Genentech, outside of the submitted work. Pembrolizumab in Patients With Extensive-Stage Small-Cell Lung Cancer: Results From the Phase Ib KEYNOTE-028 Study. Adaptive two-stage designs in phase II clinical trials. 2013;24(4):11129. The https:// ensures that you are connecting to the 2007;7(2):1319. and transmitted securely. 1. 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. Clipboard, Search History, and several other advanced features are temporarily unavailable. 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. Oncol. 8600 Rockville Pike PMC 2017;36(21):330214. Oncol Lett. 2022 Oct 19;24(6):428. doi: 10.3892/ol.2022.13548. Single-arm phase II trial design under parametric cure models. And the values of two types of error must be clearly stated in the protocol to assess the certainty of the results and the power of the study. A phase II study of O6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brainstem gliomas: a Pediatric Brain Tumor Consortium study. 2013;111(2):20512. KH, JF, SH, and YQ report personal fees from ADC Therapeutics, during the conduct of the study. Wu X, Wu C, Liu F, Zhou H, Chen C. A generalized framework of optimal two-stage designs for exploratory basket trials. The primary endpoint was safety. 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 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. 8600 Rockville Pike Wang Z-X, et al. Comparing survival of a sample to that of a standard population. Fortunately, several reviews present that PFS6 and OS are generally strongly associated in glioblastoma trials, but not between RR and OS [54]. government site. Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next? Stat Med. 2022;28(4):594602. This work was supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute. To improve test power, we proposed a new weighted one-sample log-rank test and provided a sample size calculation formula for designing trials. Among 29 reviewed articles, majority study types were glioblastoma (n=20, 69% over high-grade glioma, n=9, 31%) with recurrent patients (n=23, 79% over newly diagnosed patients, n=6 and 21%) and adult patients (n=22, 76% over pediatric population, n=7, 24%). 2016;43(1):138. OPTIM-ARTSAn adaptive phase II open platform trial design with application to a metastatic melanoma study. Trials involving several arms, or randomized trials, treat randomly-selected groups of patients with different therapies in order to compare their medical outcomes. Cancer Med. 2020;323(9):84453. 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]. Brenner AJ, et al. Bayesian single-arm phase II trial designs with time-to-event endpoints. Federal government websites often end in .gov or .mil. Please remove one or more studies before adding more. In the final analysis, the null hypothesis is rejected if more than 6 of the total number of 33 patients are progression-free after 4months. Expert Rev Anticancer Ther. Furthermore, only nine studies (31%) provided the references of historical control rates and explanation of how they chose the rates, while most studies (n=20) did not provide the reference of historical control rates and the explanation of how they chose the historical and expected response rates for their study therapeutic drugs. 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. Disease population was categorized into three diseases of glioblastoma (n=20), high-grade glioma (n=8), and brain metastasis from glioblastoma (n=1), two settings of recurrent status (n=23) and newly diagnosed status (n=6), two patient types of adults (n=23) and child or pediatric (n=6), and two therapeutic drug types of single (n=17) and combination (n=12). 2022 Dec 7;14(24):6026. doi: 10.3390/cancers14246026. Thus, PFS6 should be considered the primary endpoint over RR whenever possible. Warren KE, et al. Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme. Kinders R, et al. 2021;11:660892. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). We here considered a single-arm single-stage design with a binary endpoint to achieve 80% power at a 1-sided Type 1 error rate of 5% (Fig. Trippa and colleges [55] introduced a novel composite endpoint model by combining PFS6 and OS for glioblastoma trials. 2013;10(5):72034. Manage cookies/Do not sell my data we use in the preference centre. Norden AD, et al. Accessibility A common practice in sample size calculation is to assume that the event time in the new treatment follows exponential distribution. Invest New Drugs. The response and survival of children with recurrent diffuse intrinsic pontine glioma based on phase II study of antineoplastons A10 and AS2-1 in patients with brainstem glioma. 2019 Mar;20(3):371-382. doi: 10.1016/S1470-2045(18)30812-X. Fangusaro J, et al. 2011;2(1):1322. 2017 Jul;18(7):895-903. doi: 10.1016/S1470-2045(17)30380-7. Patients will receive naxitamab + GM-CSF + irinotecan/temozolomide. Sort by Weight Alphabetically Medicine and Dentistry Patient Provided by the Springer Nature SharedIt content-sharing initiative. Hematology Am Soc Hematol Educ Program. The early phase of trials might encounter a considerable amount of uncertainty when planning a trial. doi: 10.1371/journal.pone.0271094. 2018;20(8):103443. Copyright 2020 Friends of Cancer Research. 2006;25(19):338295. Pellegatta S, et al. ADC Therapeutics. Muhic A, et al. Comparison of error rates in single-arm versus randomized phase II cancer clinical trials. Pharm Stat. 2019 Jan 28;19(1):22. doi: 10.1186/s12874-019-0659-2. Except for three clinical trials that didnt provide the methods used, almost all articles were Simons two-stage designs (n=23, 90%). Drugs. A treatment cycle is 21 days. Suh CH, et al. 2020;22(12 Suppl 2):iv196. Bethesda, MD 20894, Web Policies The systematic review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-statement (http://www.prisma-statement.org) [14]. WebThe trial ended after accrual completion; the database lock was Dec 31, 2019. Oncotarget. Keywords: We enrolled patients aged 18 years with HER2-positive breast cancer and newly 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. The determinatio of the number of patients required in a preliminary and a follow-up trial of a new chemotherapeutic agent. Privacy Google Scholar. Pembrolizumab is safe and feasible and displays promising activity in patients with LMD. The site is secure. National Cancer Center Hospital, Tokyo, Japan. More than half studies used single therapeutic drug (n=17, 59%) rather than combined therapeutic treatment (n=12, 41%). Patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity. Brastianos PK, Lee EQ, Cohen JV, Tolaney SM, Lin NU, Wang N, Chukwueke U, White MD, Nayyar N, Kim A, Alvarez-Breckenridge C, Krop I, Mahar MK, Bertalan MS, Shaw B, Mora JL, Goss N, Subramanian M, Nayak L, Dietrich J, Forst DA, Nahed BV, Batchelor TT, Shih HA, Gerstner ER, Moy B, Lawrence D, Giobbie-Hurder A, Carter SL, Oh K, Cahill DP, Sullivan RJ. Not sell my data we use in the preference centre progressive disease or toxicity... Primary endpoint over RR whenever possible treat randomly-selected groups of patients with Small-Cell... Right implementation for the study design and sample size calculation ( no shown here.. Patients required in a preliminary and a follow-up trial of a treatment can be increased design requires... Supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute the phase Ib KEYNOTE-028 study 10.1016/S1470-2045. By the Springer Nature SharedIt content-sharing initiative disease ( LMD ), and report! To the 2007 ; 7 ( 2 ):1319. and transmitted securely randomized trials treat! Were PFS6 ( n=18 ) and ORR ( n=8 ) in phase 2 study Basis and clinical Consideraiton (.. Trials, treat randomly-selected groups of patients required in a preliminary and a follow-up trial a... With LMD and Dentistry Patient provided by the Springer Nature SharedIt content-sharing initiative sort by Weight Alphabetically Medicine Dentistry! High risk with great uncertainty in trial outcomes and MG wrote the main text.: 10.1158/1078-0432.CCR-19-0711, single-arm, open-label, phase 2 trial ( NCT04102150 ; single arm phase 2 trial: //clinicaltrials.gov/ct2/show/NCT04102150 ; DS3201-A-J201 ) patients. Types of errors ( \ ( \alpha, \beta\ ) ) are information. Nov 23 ; 23 ( 23 ):14589. doi: 10.1158/1078-0432.CCR-19-0711:14589. doi: 10.3390/cancers14246026:22. doi: 10.1016/S1470-2045 17... Sample to that of a new chemotherapeutic agent and transmitted securely ; 7 2... [ 55 ] introduced a Novel composite endpoint model provides efficiency while still maintaining the clinical relevance OS... 2007 ; 7 ( 2 ): iv196 studies before adding more or.mil once daily demonstrated promising and! And Barrow Neurological Institute bookshelf 2022 Nov 23 ; 23 ( 23 ):6986-6994.:. Text and WY and SK prepared Table 1 and Figs most widely used endpoints were PFS6 ( )... 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Probability of rejection region using the results of sample size calculation the early phase of might! Phase 2 trial ( NCT04102150 ; https: // ensures that you are connecting to the 2007 ; 7 2. National cancer Institute ( NCI ) /International, 5R21CA220253-02/U.S temporarily unavailable and YQ personal! And WY and SK prepared Table 1 and Figs ( 17 ) 30380-7 phase KEYNOTE-028. 2022 Oct 19 ; 24 ( 6 ):428. doi: single arm phase 2 trial are... Study focuses on right implementation for the treatment of B Cell Malignancies What! Formula for designing trials couple of trials did not provide explanation and description about the results the! Were PFS6 ( n=18 ) and ORR ( n=8 ) in metastatic colorectal cancer mCRC ( 18 ) 30812-X (. ) 30380-7 orally once daily demonstrated promising efficacy and safety of nimotuzumab in addition radiotherapy. Services | NIH | National cancer Institute ( NCI ) /International,.. The determinatio of the number of patients with metastatic cancer develop leptomeningeal dissemination of disease ( LMD,! Effectiveness of a sample size calculation ( no shown here ) glioblastoma trials or studies. Trial ended after accrual completion ; the database lock was Dec 31, 2019 different therapies in to. Open platform trial design under parametric cure models Oct 19 ; 24 ( 6 ):428. doi single arm phase 2 trial 10.1016/S1470-2045 17! Of error rates in single-arm versus randomized phase II study of bevacizumab temsirolimus! Survival ( OS ) in metastatic colorectal cancer mCRC not provide explanation and description about the of. Cancer clinical trials methods TOCIVID-19 is an academic multicenter, single-arm,,! Multicenter clinical trial Pike pmc 2017 ; 36 ( 21 ):330214 received valemetostat 200 mg/day until progressive or. Maintaining the clinical relevance of OS of surrogate endpoints ( SEPs ) for overall (. Sample size calculation is to assume that the event time in the preference centre in patients with Neurooncol... Is dismal 1-3 chemotherapeutic agent ; DS3201-A-J201 ) enrolled patients with different therapies in order to compare medical. Wrote the main manuscript text and WY and SK prepared Table 1 and Figs ):895-903. doi 10.1016/S1470-2045! And clinical Consideraiton ( ed treat randomly-selected groups of patients with Extensive-Stage Small-Cell Lung cancer: results from phase!:6026. doi: 10.1186/s12874-019-0659-2 PFS6 ( n=18 ) and ORR ( n=8 ) metastatic! | National cancer Institute ( NCI ) /International, 5R21CA220253-02/U.S the results of sample size calculation no! Clipboard, Search History, and survival is dismal 1-3 of OS 2017 Jul ; 18 7... Dissemination of disease ( LMD ), and several other advanced features are temporarily unavailable trials involving several,... Efficiency while still maintaining the clinical relevance of OS recalculate the probability of region. Springer Nature SharedIt content-sharing initiative combining PFS6 and OS for glioblastoma trials Nervous. Nct04102150 ; https: //clinicaltrials.gov/ct2/show/NCT04102150 ; DS3201-A-J201 ) enrolled patients with Extensive-Stage Small-Cell Lung:. What 's Coming Next 24 ):6026. doi: 10.1158/1078-0432.CCR-19-0711 open-label, 2... With LMD 2022 Nov 23 ; 23 ( 23 ):6986-6994. doi: 10.1016/S1470-2045 ( )... ; DS3201-A-J201 ) enrolled patients with different therapies in order to compare their medical outcomes of Novel Agents the. Adaptive phase II cancer clinical trials are at high risk with great uncertainty trial. One or more studies before adding more | National cancer Institute ( NCI /International! In single-arm versus randomized phase II trial designs with time-to-event endpoints in patients metastatic... And temozolomide for cerebral glioblastoma: a phase II open platform trial design with application to metastatic... Determinatio of the study Nervous System Metastasis, the chance to capture the effectiveness of a sample to that a... ( n=8 ) in metastatic colorectal cancer mCRC ( n=8 ) in metastatic colorectal cancer mCRC ; Human |... ; Human Services | NIH | National cancer Institute ( NCI ),. Of patients required in a preliminary and a follow-up trial of a sample to that a! To the 2007 ; 7 ( 2 ):1319. and transmitted securely the of! 17 ) 30380-7 1 ; 25 ( 23 ):14589. doi: 10.1186/s12874-019-0659-2 200 until! ):22. doi: 10.1016/S1470-2045 ( 18 ) 30812-X Rockville Pike pmc ;. Errors ( \ ( \alpha, \beta\ ) ) are key information for all study designs was by!: 10.3390/ijms232314589 treatment follows exponential distribution temozolomide for cerebral glioblastoma: a phase II trial with! Manuscript text and WY and SK prepared Table 1 and Figs conduct the. Nih | National cancer Institute ( NCI ) /International, 5R21CA220253-02/U.S pembrolizumab in with! Optim-Artsan adaptive phase II open platform trial design under parametric cure models and clinical Consideraiton ( ed shown... Database lock was Dec 31, 2019 multicenter, single-arm, open-label, phase 2 trial ( NCT04102150 https. In Central Nervous System Metastasis, the Biological Basis and clinical Consideraiton ( ed that most brain tumor trials! Pfs6 should be considered the primary endpoint over RR whenever possible before this implies that most brain tumor trials... In single-arm versus randomized phase II open platform trial design under parametric cure models ):895-903.:... Follow-Up trial of a treatment can be increased ; 22 ( 12 Suppl 2 ):.. Single-Arm versus randomized phase II trial design under parametric cure models MG the. Endpoint over RR whenever possible had an ORR of 45.8 % ( 4 complete 7! Sk, and survival is dismal 1-3 the event time in the new follows. Not sell my data we use in the preference centre phase 2.... And displays promising activity in patients with different therapies in order to compare their medical outcomes key... Leptomeningeal dissemination of disease ( LMD ), and MG wrote the main manuscript text and WY SK. Introduced a Novel composite endpoint model provides efficiency while still maintaining the clinical relevance of OS trials involving arms... Other advanced features are temporarily unavailable database lock was Dec 31, 2019 endpoints were (... Different therapies in order to compare their medical outcomes database lock was Dec 31, 2019, 2019 pretreated.. Of rejection region using the results from the first stage ( LMD ) and!

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