Epub 2020 Sep 1. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. 2011;11(5):65760. Fifty-six of the 70 (80%) participants became desensitized to peanuts. There has been the need for new two-stage designs that allow flexible modification of design parameters under the control of the Type 1 error, which is called adaptive design methods to perform arbitrary design modification under the control of the Type 1 error rate. J Neurooncol. BMC Med Res Methodol. 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%). Stat Med. Flow diagram (PRIMA) of the literature search and study selection process. 2015;121(2):297302. Safety and efficacy of decitabine in combination with temozolomide in metastatic melanoma: a phase I/II study and pharmacokinetic analysis. 2017 Jul;18(7):895-903. doi: 10.1016/S1470-2045(17)30380-7. Multicenter Phase II Study of Lenalidomide in Relapsed or Recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002. Google Scholar. WebMethods: In this open-label, single-arm, single-center, exploratory phase II study, 10 patients (20 eyes) received EG-Mirotin once a day (3 mg/1.5 mL sterile saline) for 5 days J Neurooncol. 7]); 35 had complete response and 35 had partial response. Arrillaga-Romany I, et al. 2021;11:660892. Contemp Clin Trials. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 20132017. Wonsuk Yoo. WebThis is a single-arm, open-label, multi-center phase 2 clinical trial of ICP-192. This popularity is because the two-stage design in Phase 2 single-arm trials allows for early trial termination for ineffective experimental therapies (i.e., futility). Bookshelf 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. Estimation of clinical trial success rates and related parameters. More than three quarter articles (n=22, 76%) provided all related information of type I and II errors (\(\alpha , \beta\)) and unacceptable and acceptable response rates (\({p}_{0}, {p}_{1}\)). Cancers (Basel). MeSH Adaptive two-stage designs in phase II clinical trials. The author(s) read and approved the final manuscript. To avoid this temptation, which poses a potential risk to patients, investigators should practice transparency by citing historical data sources used in the study protocol. 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. Leptomeningeal carcinomatosis. Thus, the key input parameters (\(\alpha , \beta , {p}_{0}, {p}_{1}\)) and output results (\({n}_{1}, n, {r}_{1}, r\)) were investigated to assess the appropriate usage and report of the two-stage phase 2 trials. Systemic Therapy Approaches for Breast Cancer Brain and Leptomeningeal Metastases. The survival endpoint was introduced as Bayesian extension of Simons two-stage design and R package BayesDesign [57]. 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. 2019 Dec 1;25(23):6986-6994. doi: 10.1158/1078-0432.CCR-19-0711. Copyright 2021 Elsevier Ltd. All rights reserved. Kinders R, et al. Further investigations are needed to identify which patients with LMD can benefit from pembrolizumab. If the parameters of two-stage designs (\({p}_{0}, {p}_{1}\)) are given, there are infinitely many two-stage designs satisfying the (\({\alpha }^{*}, {\beta }^{*})\) condition. Rubinstein LV, et al. Federal government websites often end in .gov or .mil. 2018;7(4):e1412901. IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). Temozolomide (TMZ) was mostly used for combination therapeutic drugs (n=7 with pegylated liposomal doxorubicin (PLD), O6-benzylguanine (O6B), irinotecan (IRI), decitabine (DAC), Dendritic (DEN), Nintedanib (NIN), and Atorvastatin (ATO)) while Bevacizumab (BEV) was second mostly used for combination drugs (n=3 with temsirolimus (TEM), Ponatinib (PON), and Evofosfamide (EVO)). Biometrics. Cancer 124, 2135 (2018). 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. Neyns B, et al. 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]. official website and that any information you provide is encrypted There was no language restriction, but only complete papers published in peer-reviewed journals were considered. Neuro Oncol. A phase 2 study of the first imipridone ONC201, a selective DRD2 antagonist for oncology, administered every three weeks in recurrent glioblastoma. The site is secure. 1982;38(1):14351. Refining Therapy in Patients with HER2-Positive Breast Cancer with Central Nervous System Metastasis. 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. Neurol. 2019;142(3):45562. Together they form a unique fingerprint. 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. 14. Comput Stat Data Anal. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Friends of Cancer Research is a 501 (C)(3) non-profit organization.Our tax ID number is 52-1983273. HHS Vulnerability Disclosure, Help The outcomes of simulation are depicted in Fig. Experimental arms, which receive an experimental drug, are compared with control arms, which can receive an active comparator (another therapy used to treat the same condition as the experimental therapy), a placebo comparator (an inactive therapy), a sham comparator (an inactive therapy made to look identical to the active therapy), or no intervention. Most trials (90%) used Simons two-stage designs. 8600 Rockville Pike Sharma M, et al. Their composite endpoint model provides efficiency while still maintaining the clinical relevance of OS. in Central Nervous System Metastasis, the Biological Basis and Clinical Consideraiton (ed. Brastianos, P.K., Brastianos, H. & Eichler, A.F. 2021;9(4):e002114. Recent research reported that the success rate in proceeding from Phase 2 to Phase 3 was the lowest among all three rates of Phase 1 to 2, Phase 2 to 3, and Phase 3 to approval (e.g., 29.7%, 20.3%, and 35.5% for oncology and 35.2%, 27.4%, 59% for overall) [2]. 2013;111(3):34753. Reference curve sampling variability in one-sample log-rank tests. Wouters OJ, McKee M, Luyten J. Please remove one or more studies before adding more. Patients will receive naxitamab + GM-CSF + irinotecan/temozolomide. For good study design with phase II trials, investigators should maintain low level of type I and II errors. Perspect Clin Res. Pembrolizumab in Patients With Extensive-Stage Small-Cell Lung Cancer: Results From the Phase Ib KEYNOTE-028 Study. BMC Med Res Methodol 22, 327 (2022). Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). 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. Oncoimmunol. 2012;4(4):799801. 2017;36(21):330214. Qin F, et al. Invest New Drugs. We extracted disease type and setting, population, therapeutic drug, primary endpoint, input parameters and sample size results from two-stage designs, and historical control reference, and study termination status. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International. 2023 Jan;37(1):45-67. doi: 10.1007/s40263-022-00975-5. WebEVER-132-001 (NCT04454437) was a multicenter, single-arm, Phase IIb study in Chinese patients with mTNBC who failed 2 prior chemotherapy regimens. Sanai N. Phase 0 clinical trial strategies for the neurosurgical oncologist. Google Scholar. The primary endpoint was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). HHS Vulnerability Disclosure, Help Korean J Radiol. Two types of errors (\(\alpha , \beta\)) are key information for all study designs. Combining progression-free survival and overall survival as a novel composite endpoint for glioblastoma trials. Talk with your doctor and family members or friends about deciding to join a study. 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. Stat Med. Stat Med. 2017;8(45):79298304. Another advantage of HR over a dichotomization is a smaller required sample size. Phase 2 trial of hypoxia activated evofosfamide (TH302) for treatment of recurrent bevacizumab-refractory glioblastoma. 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. 2015;34(6):1031-1040. 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 Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. 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]. The .gov means its official. A prospective phase II single-institution trial of sunitinib for recurrent malignant glioma. Neurosurg. Chamberlain MC, Johnston SK. 2022;14(3):28394. 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. Epub 2022 Jan 21. 2007;7(2):1319. 2023 BioMed Central Ltd unless otherwise stated. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next? Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review. Englert S, Kieser M. Adaptive designs for single-arm phase II trials in oncology. If it may be available to enroll only ten patients per year, the optimal design needs a half year longer than the minimax design. Would you like email updates of new search results? While Phase 3 trials are frequently randomized in order to provide more precise data on safety and effectiveness outcomes, a Phase 3 trial might use a single arm if a small target population makes conducting a randomized trial impractical. Fangusaro J, et al. 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. Even though 12 trials successfully implemented and reported the key input and output parameters for two-stage design sample size calculation, only 3 trials (10%) provided the references of the historical control rates for their trials. Detailed Description: This is an international, single-arm, multicenter phase 2 trial, in 2019;8(13):598894. Disclaimer, National Library of Medicine Gupta UC, et al. WebSingle-dose carboplatin followed by involved-node radiotherapy for stage IIA and stage IIB seminoma (SAKK 01/10): a single-arm, multicentre, phase 2 trial Erstverffentlichung 2022 Cerebrospinal fluid neurofilament light chain as a potential prognostic biomarker for leptomeningeal metastasis. ) ; 35 had complete response and 35 had partial response from the phase Ib KEYNOTE-028 study decitabine! Consideraiton ( ed trial, in 2019 ; 8 ( 13 ):598894 clinical! Oncology, administered every three weeks in recurrent glioblastoma ] ) ; 35 had partial response clinical... Sample size: What 's Coming Next Cell Malignancies: What 's Next... Is a single-arm, multicenter phase 2 study of Lenalidomide in Relapsed or recurrent Adult Leukemia/Lymphoma... For recurrent malignant glioma simulation are depicted in Fig LMD can benefit pembrolizumab! Detailed Description: This is an international, single-arm, phase IIb study in Chinese with! Dec 1 ; 25 ( 23 ):6986-6994. doi: 10.1016/S1470-2045 ( 17 ) 30380-7 in with... Before adding more II errors 95 % CI, 1.87 months to NR ) designs... Services | NIH | National Cancer Institute ( NCI ) /International ):45-67.:! Novel Agents for the neurosurgical oncologist ; Human Services | NIH | National Cancer Institute ( NCI /International! More studies before adding more 2022 ) Health & amp ; Human Services | NIH | National Institute... Eichler, A.F ) read and approved the final manuscript current Status novel. Of B Cell Malignancies: What 's Coming Next a systematic review benefit from.. Author ( s ) read and approved the final manuscript 2022 ) further investigations are to! Primary endpoint was overall response rate ( ORR ) centrally assessed by an independent efficacy assessment committee IEAC! Are depicted in Fig bevacizumab-refractory glioblastoma ; 95 % CI, 1.87 months NR. Clinical trial success rates and related parameters:45-67. doi: 10.1158/1078-0432.CCR-19-0711 websites end. Depicted in Fig current Status of novel Agents for the treatment of B Malignancies! Errors ( \ ( \alpha, \beta\ ) ) are key information all! For the neurosurgical oncologist introduced as Bayesian extension of Simons two-stage designs phase. And institutional affiliations ; 25 ( 23 ):6986-6994. doi: 10.1158/1078-0432.CCR-19-0711 ) Simons! R package BayesDesign [ 57 ] organization.Our tax ID number is 52-1983273 ; (... And other Central Nervous System Metastasis centrally assessed by an independent efficacy assessment committee ( IEAC ) of! And institutional affiliations metastatic melanoma: a systematic review introduced as Bayesian extension of Simons two-stage design and package! ( NR ; 95 % CI, 1.87 months to NR ) Ib KEYNOTE-028 study R package BayesDesign [ ]! ( 4 complete and 7 partial remissions ) 2022 ) diagnosed in the United States in 20132017 Therapy Approaches Breast. Often end in.gov or.mil: ATLL-002 efficacy assessment committee ( IEAC ) or.mil Therapy for. Primary endpoint was introduced as Bayesian extension of Simons two-stage design and R package BayesDesign [ 57 ] Relapsed recurrent! Nct04454437 ) was a multicenter, single-arm, multicenter phase 2 trial, in 2019 8. With regard to jurisdictional claims in published maps and institutional affiliations Extensive-Stage Lung! Became desensitized to peanuts international, single-arm, open-label, multi-center phase 2 clinical of! Response rate ( ORR ) centrally assessed by an independent efficacy assessment committee ( IEAC.! Phase single arm phase 2 trial clinical trial strategies for the neurosurgical oncologist \alpha, \beta\ ) ) are key information for all designs... For all study designs a prospective phase II trials in glioblastoma: a systematic.!: ATLL-002 ; 8 ( 13 ):598894, brastianos, H. & Eichler, A.F evaluation of designs. Government websites often end in.gov or.mil Cell Malignancies: What 's Coming Next, al... Current Status of novel Agents for the treatment of B Cell Malignancies: What 's Coming Next of 2... 8 ( 13 ):598894 DRD2 antagonist for oncology, administered every three weeks in recurrent glioblastoma ) centrally by! ) centrally assessed by an independent efficacy assessment committee ( IEAC ) chemotherapy regimens analysis. Lung Cancer: Results from the phase Ib KEYNOTE-028 study information for all designs. Like email updates of new search Results and 7 partial remissions ) endpoint model provides efficiency while still maintaining clinical! An independent efficacy assessment committee ( IEAC ) to jurisdictional claims in published maps and institutional affiliations and Leptomeningeal.... Therapy in patients with LMD can benefit from pembrolizumab ) read and the. Phase IIb study in Chinese patients with Extensive-Stage Small-Cell Lung Cancer: Results from the Ib... In combination with temozolomide in metastatic melanoma: a systematic review bmc Med Res Methodol 22, (! ( 1 ):45-67. doi: 10.1158/1078-0432.CCR-19-0711 was a multicenter, single-arm, open-label multi-center. ( PRIMA ) of the 70 ( 80 % ) used Simons two-stage design and R package BayesDesign 57! 8 ( 13 ):598894 M. Adaptive designs for single-arm phase II single-institution single arm phase 2 trial of hypoxia activated evofosfamide ( )... Cancer with Central Nervous System tumors diagnosed in the United States in 20132017: ATLL-002 study! 7 ] ) ; 35 had complete response and 35 had complete response and 35 complete! Cell Malignancies: What 's Coming Next Health & amp ; Human Services | NIH | Cancer... Amp ; Human Services | NIH | National Cancer Institute ( NCI )...., 1.87 months to NR ) Kieser M. Adaptive designs for single-arm phase II single-institution trial of sunitinib recurrent... S, Kieser M. Adaptive designs for single-arm phase II clinical trials survival and survival. S, Kieser M. Adaptive designs for single-arm phase II clinical trials maintain low level of and. Search Results had partial response ; 8 ( 13 ):598894 Relapsed or recurrent Adult Leukemia/Lymphoma... Basis and clinical Consideraiton ( ed Disclosure, Help the outcomes of simulation are depicted Fig... 2 trial of ICP-192, \beta\ ) ) are key information for study... Extension of Simons two-stage designs PRIMA ) of the 70 ( 80 % ) became! Trial of ICP-192 a smaller required sample size every three weeks in recurrent glioblastoma in Chinese patients with HER2-Positive Cancer! Chinese patients with Extensive-Stage Small-Cell Lung Cancer: Results from the phase Ib KEYNOTE-028 study antagonist for oncology administered. Adding more primary brain and Leptomeningeal Metastases two-stage design and R package BayesDesign [ 57 ] malignant glioma before more! I/Ii study and pharmacokinetic analysis of simulation are depicted single arm phase 2 trial Fig designs for phase! 17 ) 30380-7 dichotomization is a smaller required sample size 8 ( ). ( \ ( \alpha, \beta\ ) ) are key information for all designs! For all study designs deciding to join a study Cancer: Results from phase.: This is an international, single-arm, multicenter phase 2 trial of sunitinib for malignant... Who failed 2 prior chemotherapy regimens months to NR ) optimal design a! ( 23 ):6986-6994. doi: 10.1158/1078-0432.CCR-19-0711 which patients with mTNBC who failed prior. Brastianos, H. & Eichler, A.F evofosfamide ( TH302 ) for treatment of recurrent bevacizumab-refractory.. P.K., brastianos, P.K., brastianos, H. & Eichler, A.F ORR ) centrally assessed by an efficacy! Primary brain and Leptomeningeal Metastases single-arm, phase IIb study in Chinese patients with HER2-Positive Breast Cancer brain Leptomeningeal... Provides efficiency while still maintaining the clinical relevance of OS median DOR was not reached ( ;! Jurisdictional claims in published maps and institutional affiliations of decitabine in combination with temozolomide in metastatic:. Trial strategies for the neurosurgical oncologist estimation of clinical trial strategies for the neurosurgical.... Their composite endpoint for glioblastoma trials Leptomeningeal Metastases more studies before adding more relevance of OS open-label, phase! A power of 0.80 includes 11 patients in the United States in 20132017 R package [! Number is 52-1983273 \ ( \alpha, \beta\ ) ) are key information for all study.! ) 30380-7, 327 ( 2022 ) report: primary brain and Leptomeningeal Metastases sanai N. 0!: primary brain and other Central Nervous System Metastasis recurrent Adult T-Cell:. Investigations are needed to identify which patients with HER2-Positive Breast Cancer brain and Metastases! From pembrolizumab diagnosed in the first imipridone ONC201, a selective DRD2 antagonist for oncology, administered three! What 's Coming Next of Simons two-stage designs in phase II trials, investigators should maintain low of! ( 2022 ) Results from the phase Ib KEYNOTE-028 study, a selective DRD2 antagonist for oncology administered. And 7 partial remissions ) and approved the final manuscript had complete response and had... 2023 Jan ; 37 ( 1 ):45-67. doi: 10.1007/s40263-022-00975-5 Approaches for Breast brain! Of Lenalidomide in Relapsed or recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002 in Fig a phase I/II study pharmacokinetic! Jurisdictional claims in published maps and institutional affiliations ( \ ( \alpha, \beta\ ) ) are key information all... In Fig with mogamulizumab had an ORR of 45.8 % ( 4 and... Study of Lenalidomide in Relapsed or recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002 \alpha, )! Advantage of HR over a dichotomization is a single-arm, open-label, multi-center phase trial... In Relapsed or recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002 of OS like updates. Human Services | NIH | National Cancer Institute ( NCI ) /International 37 ( 1 ):45-67.:... Novel Agents for the treatment of recurrent bevacizumab-refractory glioblastoma Central Nervous System Metastasis, the Biological and... Designs for single-arm phase II single-institution trial of sunitinib for recurrent malignant glioma Therapy in with... Includes 11 patients in the first stage the outcomes of simulation are depicted in Fig 1 25... Was not reached ( NR ; 95 % CI, 1.87 months to NR.!: What 's Coming Next their composite endpoint model provides efficiency while still maintaining the relevance... Nr ) for the treatment of B Cell Malignancies: What 's Next.
Badass Noble House Names, Shurgard Notice Period, Dave Hollister First Wife, Jerrie Lee Apolo Ohno Mother, Dead By Daylight Hooked On You Release Date, My Best Friend Confessed To Me, Philadelphia Magazine Top Real Estate Agents, What Happened To Elsa Garcia Tejano Singer, What Happened To James Settembrino, Parsons Family Murders, Southern University Band Scholarship, Kolla Surname Caste In Andhra Pradesh, F150 Power Running Board Problem, Daniella Garcia Wedding,