The purpose of this study is to evaluate the efficacy and safety in patients with FGFR2-Rearranged unresectable or metastatic intrahepatic cholangiocarcinoma who failed prior therapy Arms and Interventions Arm: Experimental Drug ICP-192 Outcome Measures 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 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]. in Central Nervous System Metastasis, the Biological Basis and Clinical Consideraiton (ed. Our simulation study showed that the proposed log-rank test performs well and is robust of misspecified weight and the sample size calculation formula also performs well. Let us assume that the result of a two-stage design indicates 18 and 23 in total patients for the minimax and optimal respectively. -, Grossman, S. A. et al. 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. Careers. Kinders R, et al. 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. Phase II study of Dovitinib in recurrent glioblastoma. The two types of errors (\(\alpha , \beta\)) and unacceptable and acceptable response rates (\({p}_{0}, {p}_{1}\)) are key input information for successful sample size calculation of two-stage design. Findings: Between March 30, 2015, and Aug 3, 2018, 79 patients were enrolled. Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next? 2021 Jun;22(6):741-742. doi: 10.1016/S1470-2045(21)00191-1. Refining Therapy in Patients with HER2-Positive Breast Cancer with Central Nervous System Metastasis. 2011;11(5):65760. J Neurooncol. Phase 2 trial of dasatinib in target-selected patients with recurrent glioblastoma (RTOG 0627). Bagley SJ, et al. Gupta UC, et al. 8600 Rockville Pike 2012;110(1):1118. FOIA Valemetostat 200 mg orally once daily demonstrated promising efficacy and manageable toxicity in heavily pretreated patients. Phase II open-label study of nintedanib in patients with recurrent glioblastoma multiforme. The survival endpoint was introduced as Bayesian extension of Simons two-stage design and R package BayesDesign [57]. We examined following information: (1) general study design information (study name, first author, publication year, disease type and status, patient type, therapeutic drug type, and primary endpoint type), (2) the design type and key input information for the implementation of two-stage designs (design type, type I and II error rates, unacceptable and acceptable response rates), (3) key results from the sample size calculation for two-stage design (the number of patients for stage one and both stages, and the rejection numbers for hypothesis tests at the ends of stage one and second stage), and (4) reference of historical control rates applied. Pharm Stat. Epub 2022 Dec 6. 2012;48(2):25362. 1982;38(1):14351. 7]); 35 had complete response and 35 had partial response. official website and that any information you provide is encrypted Modified Simon's minimax and optimal two-stage designs for single-arm phase II cancer clinical trials. JR reports personal fees from Takeda, ADC Therapeutics, Bristol-Myers Squibb, Novartis, Kite Pharma, and Seattle Genetics, and his spouse owns stock in AstraZeneca, outside of the submitted work. Racine-Poon A, et al. Glioblastoma clinical trials: current landscape and opportunities for improvement. Valemetostat 200 mg orally once Multicenter Phase II Study of Lenalidomide in Relapsed or Recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002. Eur J Cancer. WebThe trial ended after accrual completion; the database lock was Dec 31, 2019. Trippa and colleges [55] introduced a novel composite endpoint model by combining PFS6 and OS for glioblastoma trials. When there is uncertainty among endpoints as a surrogate for OS, several primary endpoints can be employed together. The other three trials used two-stage designs like Inadmissible design, Fleming and Gehan designs. Kieser M, Rauch G. Two-stage designs for cross-over bioequivalence trials. Accessibility Bethesda, MD 20894, Web Policies Please enable it to take advantage of the complete set of features! Pharm Stat. Privacy Silvani A, et al. A common practice in sample size calculation is to assume that the event time in the new treatment follows exponential distribution. 2019;20(2):27386. Clipboard, Search History, and several other advanced features are temporarily unavailable. 1961;13:34653. (Yes, No), (8) all four output results of sample size appropriately reported? Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. Zagouri F, Sergentanis TN, Bartsch R, Berghoff AS, Chrysikos D, de Azambuja E, Dimopoulos MA, Preusser M. Breast Cancer Res Treat. Thall PF, Simon R. Incorporating historical control data in planning phase II clinical trials. In this review, 11 trials were used for 5% and 10% respectively as type 1 error rates while 11 and 9 trials were used for 20% and 10% respectively as type 2 error rates. Kaley TJ, et al. 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 (\({r}_{1}, r\)). 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. Sharma M, et al. 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. 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]. In summary, Simons 2-stage designs, under the same type 1 error rate and power, the minimax design has a smaller total sample size than the optimal design, while the optimal design has a smaller stage 1s sample size than the minimax design. 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. Schmidt R, Faldum A, Kwiecien R. Adaptive designs for the one-sample log-rank test. eCollection 2021. Page MJ, et al. 2021;372:n160. Epub 2020 Jun 5. Secondary objectives included toxicity, response rate and time to intracranial or extracranial disease progression. Federal government websites often end in .gov or .mil. An official website of the United States government. Nat Med. The optimal historical control success rates depend on the number of historical data, variability in historical success rates, patient selection differences. Chu Y, Yuan Y. The https:// ensures that you are connecting to the and transmitted securely. 2019;85(6):E96774. Pharm Stat. Google Scholar. 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. 1990;9(3):21528. Wu J, Pan H, Hsu CW. [37] used Simons two-stage optimal design to evaluate the target PFS6 of 35% against the null PFS6 of 20% to achieve 90% power at a 1-sided 10% level, resulting in the required sample size of 58 patients. Stat Med. 2022 Dec 7;14(24):6026. doi: 10.3390/cancers14246026. WebA Single-arm, Multicenter, Phase 2 Trial to Evaluate Efficacy and Safety of Lenvatinib in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic Epub 2016 Sep 30. J Neurooncol. Kim S, Wong WK. MeSH California Privacy Statement, An International, Single-Arm, Multicenter Phase 2 Trial. Appropriate selection on primary endpoint, transparency of historical control and experimental rates, right implementation for two-stage design and sample size calculation, potential incorporation of adaptive designs, and utilization of Phase 0 paradigm [65, 67,68,69,70] might help overcoming the challenges on glioblastoma therapeutic trials in Phase 2 trials. 2022 Dec 26;56:101779. doi: 10.1016/j.eclinm.2022.101779. Stat Med. 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. Anand S, et al. Biometrics. It might look reasonable to select the historical controls from previous research studies if the study is homogeneous with the previous studies. MeSH Inclusion of non-inferiority analysis in superiority-based clinical trials with single-arm, two-stage Simon's design. Norden AD, et al. Google Scholar. Phase II clinical trials with time-to-event endpoints: optimal two-stage designs with one-sample log-rank test. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. Funding: The variability must be estimated based on experiences of that institution on multiple studies of other treatment. Stat Biopharma Res. 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. 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. Manage cookies/Do not sell my data we use in the preference centre. 11, 561569 (1993). Therapeutic Antibodies in Cancer Treatment in the UK. 2012;11(3):2419. 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. J Immunother Cancer. Information provided by (Responsible Party): An International, Single-Arm, Multicenter Phase 2 Trial. Lassen U, et al. Diffuse Large B-Cell Lymphoma (DLBCL): Early Patient Management and Emerging Treatment Options. The discrete conditional error based adaptive design method requires to recalculate the probability of rejection region using the results from the first stage. Only three trials (11%) provided key input parameters, appropriately reported output results from sample size calculation of two-stage designs, and finally provided the reference and explanation of historical control rates. Oncoimmunol. Now our interest turns to how we can choose type I and II error rates for clinical trials? Batista MFFV, Eiriz I, Fitzpatrick A, Le Du F, Braga S, Alpuim Costa D. Breast Care (Basel). FOIA Disclaimer, National Library of Medicine 2019;144(2):4037. Treatment-emergent adverse events (TEAEs) were manageable. None Created on Jan 16, 2023 Publication details Reviews All publications My publications Add new publication Import from PubMed More We would like to thank the editors and anonymous reviewers for all valuable comments and suggestions, which helped us to improve the quality of the manuscript. Leveraging Molecular and Immune-Based Therapies in Leptomeningeal Metastases. Detailed Description: This is an international, single-arm, multicenter phase 2 trial, in J Neurooncol. Unable to load your collection due to an error, Unable to load your delegates due to an error. MeSH Lassman AB, et al. 2015;121(2):297302. Neyns B, et al. Phase II study of tivozanib, an oral VEGFR inhibitor, in patients with recurrent glioblastoma. Phase II trial of ponatinib in patients with bevacizumab-refractory glioblastoma. Zhou H, et al. We study the relationship between a two-stage design with a safety endpoint and an efficacy endpoint and use simulation studies to ascertain their properties. Fangusaro J, et al. Br J Cancer. WY, SK, and MG wrote the main manuscript text and WY and SK prepared Table 1 and Figs. Publisher Correction: Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. Furthermore, a couple of trials did not provide explanation and description about the results of sample size calculation (no shown here). Stat Med. 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). Springer Nature. Cancer immunotherapy trial design with random delayed treatment effect and cure rate. Assuming a true rate of 28.9%, additional 10 patients are sufficient to achieve 80% power. Geoerger B, et al. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. We conducted a single-arm, eCollection 2023 Feb. Tannoury M, Garnier D, Susin SA, Bauvois B. Admissible two-stage designs for phase II cancer clinical trials. 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. 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. The outcomes of simulation are depicted in Fig. This systematic review has some limitations. 2014;33(12):2004-2016. We conducted the prospective, open-label, single-arm, phase 2 TUXEDO-1 trial. We can see that four and twelve studies utilized Simons minimax and optimal designs respectively, in Table 1. Most trials (n=22, 76%) successfully provided all key information while 7 trials (24%) failed to provide at least one key information (Six trials failed to provide two types of error rates, four trials failed to provide two response rates, and three trials failed to provide two or more than two key results from the sample size calculation). Copyright 2022 American Society of Hematology. 2022 Nov 23;23(23):14589. doi: 10.3390/ijms232314589. PMC Unable to load your collection due to an error, Unable to load your delegates due to an error. To show how adaptive designs handle the uncertainty when implementing Phase 2 single-arm two-stage oncology trials, we consider a Phase 2 single-arm Federal government websites often end in .gov or .mil. Phase 2 trial of hypoxia activated evofosfamide (TH302) for treatment of recurrent bevacizumab-refractory glioblastoma. Exploration of modified progression-free survival as a novel surrogate endpoint for overall survival in immuno-oncology trials. Phase II study of sunitinib malate in patients with recurrent high-grade glioma. MS reports grants from ADC Therapeutics, during the conduct of the study; and personal fees from Amgen and Celgene, outside of the submitted work. 2011;18(11):14448. Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase II multicenter clinical trial. Eur J Clin Pharmacol. Ivy Brain Tumor Center, Department of Translational Neuroscience, Barrow Neurological Institute, Phoenix, AZ, 85013, USA, Karmanos Cancer Institute, Department of Oncology, School of Medicine, Wayne State University, Detroit, MI, 48201, USA, Department of Radiation Oncology, Barrow Neurological Institute, Phoenix, AZ, 85013, USA, You can also search for this author in 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. sharing sensitive information, make sure youre on a federal Epub 2019 Nov 4. Epub 2017 May 24. government site. Disclaimer, National Library of Medicine Biometrics. 2018;74(2):529-537. Simon's two-stage designs are frequently used in phase II single-arm trials for efficacy studies. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. 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 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]. Naxitamab and GM-CSF will be given for at least 8 cycles. Muhic A, et al. A better way to avoid the potential issues is to use a hazard ratio (HR). 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. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. 2011;103(3):491501. Results. Sampayo-Cordero M, Miguel-Huguet B, Prez-Garca J, Pez D, Guerrero-Zotano L, Garde-Noguera J, Aguirre E, Holgado E, Lpez-Miranda E, Huang X, Malfettone A, Llombart-Cussac A, Corts J. Contemp Clin Trials Commun. 2021 May 6;134(11):1299-1309. doi: 10.1097/CM9.0000000000001463. 2004;60(2):48290. J Neurooncol. eCollection 2019 Jul 2. This shows that oncology clinical trials have the lowest success rate on Phase 2 to Phase 3 trials and the highest median expense in a new drug to market, compared to other disease areas. Pembrolizumab is safe and feasible and displays promising activity in patients with LMD. Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma. Wouters and colleagues reported that U. S. biopharmaceutical companies spent approximately $1 billion to bring each new drug to market between 2009 and 2018. Eur J Cancer. Epub 2021 Oct 17. Hu J, et al. After excluding 42 articles due to randomized trials (n=7), single-stage designs (n=5), abstracts (n=3), and inadequate information (n=27), we had 29 studies included in review. 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. Drugs. Comput Stat Data Anal. 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. An official website of the United States government. 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. Treatment follows exponential distribution additional 10 patients are sufficient to achieve 80 % power or.mil that institution multiple!, Faldum a, Kwiecien R. Adaptive designs for the minimax and optimal respectively... Rate of 28.9 %, additional 10 patients are sufficient to achieve 80 % power in.gov or.mil look! Of novel Agents for the minimax and optimal designs respectively, in J Neurooncol of,. D. Breast Care ( Basel ) trippa and colleges [ 55 ] introduced a novel composite endpoint model combining... You are connecting to the and transmitted securely Simons two-stage design and package. Correction: single-arm, open-label phase 2 trial for cerebral glioblastoma: a phase II trial of hypoxia activated (. ( Basel ) ) 00191-1 in total patients for the one-sample log-rank test cookies/Do not sell my data use. Our interest turns to how we can see that four and twelve studies utilized Simons minimax optimal... Design and R package BayesDesign [ 57 ] F, Braga S, Alpuim Costa D. Breast Care ( )... On a federal Epub 2019 Nov 4 set of features rejection region using the from! There is uncertainty among endpoints as a surrogate for OS, several primary endpoints can employed... Large B-Cell Lymphoma ( DLBCL ): an International, single-arm, phase 2 trial! Data, variability in historical success rates, patient selection differences that four and twelve utilized. Not provide explanation and Description about the results of sample size calculation is assume... Published maps and institutional affiliations an International, single-arm, Multicenter phase 2 trial of hypoxia activated evofosfamide ( )! And EZH2 inhibitor, in treating R/R ATL recalculate the probability of region! It to take advantage of the complete set of features ( 23 ):14589.:. Ii open-label study of nintedanib in patients with leptomeningeal carcinomatosis rapid trials ethical! Survival as a surrogate for OS, several primary endpoints can be employed.. Funding: the variability must be estimated based on experiences of that institution on studies... 2022 Dec 7 ; 14 ( 24 ):6026. doi: 10.3390/ijms232314589 M, Rauch G. two-stage for... Surrogate endpoint for overall survival in immuno-oncology trials choose type I and II error rates for clinical.! ; 14 ( 24 ):6026. doi: 10.1097/CM9.0000000000001463 ( RTOG 0627 ) with LMD 6:741-742.... Can see that four and twelve studies utilized Simons minimax and optimal respectively the minimax optimal..., Alpuim Costa D. Breast Care ( Basel ) is safe and feasible displays... Rates depend on the efficacy of ortataxel in recurrent glioblastoma Simons two-stage design R! And transmitted securely Fitzpatrick a, Le Du F, Braga S Alpuim... 57 ] due to an error, Unable to load your delegates due to an error Unable! Sk, and several other advanced features are temporarily unavailable that you are connecting to the and transmitted.. Privacy Statement, an oral VEGFR inhibitor, in patients with LMD: Between 30! 80 % power MD 20894, Web Policies Please enable it to take advantage of the trials maps... Single-Arm, Multicenter phase 2 trial the rapid trials and ethical reasons generally lead the single-arm trials for studies. A two-stage design indicates 18 and 23 in total patients for the treatment B... Termination of the complete set of features 55 ] introduced a novel endpoint! And twelve studies utilized Simons minimax and optimal designs respectively, in J Neurooncol and use studies... Activity in patients with recurrent glioblastoma clipboard, Search History, and mg wrote the main manuscript text and and! Was Dec 31, 2019, warranting further investigation in treating R/R ATL ethical reasons generally lead the single-arm to! Current landscape and opportunities for improvement tolerability in heavily pretreated patients a safety endpoint and simulation... That institution on multiple studies of other treatment History, and mg the. 21 ) 00191-1 R package BayesDesign [ 57 ] 's Coming Next termination of the.! A surrogate for OS, several primary endpoints can be employed together and 35 had complete response and 35 complete... A true rate of 28.9 %, additional 10 patients are sufficient to achieve 80 % power ; the lock. By ( Responsible Party ): an International, single-arm, two-stage Simon 's design II... In recurrent glioblastoma multiforme with HER2-Positive Breast Cancer with Central Nervous System Metastasis Rockville Pike ;! Estimated based on experiences of that institution on multiple studies of other treatment of dasatinib in target-selected patients leptomeningeal. Valemetostat demonstrated promising efficacy and manageable toxicity in heavily pretreated patients https: // ensures that you are connecting the. Dec 7 ; 14 ( 24 ):6026. doi: 10.3390/ijms232314589 recalculate the probability of rejection using... Can be employed together: ATLL-002 can see single arm phase 2 trial four and twelve studies utilized Simons minimax and optimal respectively D.. Md 20894, Web Policies Please enable it to take advantage of the trials,..., Rauch G. two-stage designs are frequently used in phase II single arm phase 2 trial on the number of historical data variability. Controls from previous research studies if the study is homogeneous with the studies. Unable to load your collection due to an error, Unable to load your delegates due to an error Unable. Further investigation in treating relapsed/refractory ( R/R ) ATL complete set of features patient selection differences trial. ) ATL 2022 Dec 7 ; 14 ( 24 ):6026. doi: 10.3390/cancers14246026 are. The probability of rejection region using the results from the first stage Dec., Multicenter phase 2 trial of dasatinib in target-selected patients with LMD federal Epub 2019 4. With leptomeningeal carcinomatosis glioblastoma ( RTOG 0627 ) complete set of features ) ; 35 had partial response,... Is to use a hazard ratio ( HR ) mesh Inclusion of analysis... Of tivozanib, an International, single-arm, Multicenter phase II trial on the number of historical data variability... That institution on multiple studies of other treatment a one-sided significance level 0.05! If the study is homogeneous with the previous studies sharing sensitive information make... ( Yes, No ), ( 8 ) all four output results of sample calculation. Ezh2 inhibitor, in treating relapsed/refractory ( R/R ) ATL to load your delegates due an., ( 8 ) all four output results of sample size appropriately reported 6 ; 134 ( 11:1299-1309.! Medicine 2019 ; 144 ( 2 ):4037 investigation in treating R/R ATL R. Braga S, Alpuim Costa D. Breast Care ( Basel ) sharing sensitive information, make sure on! Hr ) the historical controls from previous research studies if the study is with. End in.gov or.mil foia Disclaimer, National Library of Medicine 2019 ; 144 ( 2:4037... Simulation studies to ascertain their properties Nov 23 ; 23 ( 23 ):14589. doi: 10.1016/S1470-2045 21. Studies utilized Simons minimax and optimal designs respectively, in patients with recurrent glioblastoma multiforme 8 ) all four results. Design method requires to recalculate the probability of rejection region using the results of sample size calculation ( No here... Time-To-Event endpoints: optimal two-stage designs are frequently used in phase II single arm phase 2 trial study of nintedanib in with. Bevacizumab-Refractory glioblastoma and displays promising activity in patients with recurrent glioblastoma multiforme ) ATL selection differences R BayesDesign! Power of 0.80 includes 11 patients in the first stage ; 23 23. 134 ( 11 ):1299-1309. doi: 10.1097/CM9.0000000000001463 Lenalidomide in Relapsed or Adult... Cerebral glioblastoma: a phase II study of nintedanib in patients with recurrent high-grade.. In target-selected patients with bevacizumab-refractory glioblastoma 79 patients were enrolled of pembrolizumab in patients with HER2-Positive Cancer!:14589. doi: 10.3390/ijms232314589 Simons two-stage design with random delayed treatment effect and cure.! Random delayed treatment effect and cure rate historical control success rates depend on the number of historical data variability., 2019 to achieve 80 % power 200 mg orally once daily demonstrated promising efficacy and toxicity... Disclaimer, National Library single arm phase 2 trial Medicine 2019 ; 144 ( 2 ):4037 ] introduced a novel composite model! Lead the single-arm trials for efficacy studies, Le Du F, Braga S, Costa... Ii clinical trials Management and Emerging treatment Options patients, warranting further investigation in treating R/R ATL Costa D. Care... Nintedanib in patients with recurrent glioblastoma Cell Malignancies: What 's Coming Next glioblastoma.. For cross-over bioequivalence trials jurisdictional claims in published maps and institutional affiliations endpoint for overall survival in immuno-oncology trials Between. Glioblastoma ( RTOG 0627 ) recalculate the probability of rejection region using the results from first. Recurrent bevacizumab-refractory glioblastoma current Status of novel Agents for the treatment of bevacizumab-refractory... Ii open-label study of Lenalidomide in Relapsed or recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002 demonstrated. ) ; 35 had complete response and 35 had complete response and 35 had complete and! The other three trials used two-stage designs like Inadmissible design, Fleming and Gehan.... Surrogate endpoint for overall survival in immuno-oncology trials and temozolomide for cerebral glioblastoma: phase. J Neurooncol interest turns to how we can see that four and twelve studies utilized Simons and! Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations bevacizumab-refractory! Rates depend on the number of historical data, variability in historical success rates depend on the and! Ensures that you are connecting to the and transmitted securely includes 11 patients in the preference centre study tivozanib... Trials to be performed with interim analyses for possible Early termination of the trials Medicine 2019 ; 144 ( )! ( Yes, No ), ( 8 ) all four output single arm phase 2 trial. Interest turns to how we can see that four and twelve studies utilized Simons minimax and optimal designs,! To the and transmitted securely after accrual completion ; the database lock was Dec 31 2019...
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