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. This systematic review has some limitations. Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review. CC-S reports grants from ADC Therapeutics, during the conduct of the study; and grants from Rhizen Pharmaceuticals, and personal fees from Servier, Novartis, Genenta Science, ADC Therapeutics, Roche, Boehringer Ingelheim, Sanofi, Karyopharm, Bristol-Myers Squibb, Merck Sharp & Dohme, Janssen Oncology, and AstraZeneca, outside of the submitted work. An official website of the United States government. eCollection 2022. 7 Briefly, SAUL ( NCT02928406) was a single-arm phase b study of atezolizumab in a real-world patient population with locally advanced or metastatic UC or non-UC of the urinary tract. Optimized image-based surrogate endpoints in targeted therapies for glioblastoma: a systematic review and meta-analysis of phase iii randomized controlled trials. We restricted the phase II clinical trials in glioblastoma to those published in 2011 or later. -, Wang, N., Bertalan, M. S. & Brastianos, P. K. Leptomeningeal metastasis from systemic cancer: review and update on management. Oncol. 2020;22(12 Suppl 2):iv196. The sample size calculation for the two-stage designs is determined based on the historical control rate and difference between the two rates (\({p}_{0}, {p}_{1}\)). and transmitted securely. The primary endpoint was safety. Right implementation for two-stage design and sample size calculation, transparency of historical control and experimental rates, appropriate selection on primary endpoint, potential incorporation of adaptive designs, and utilization of Phase 0 paradigm might help overcoming the challenges on glioblastoma therapeutic trials in Phase 2 trials. 2021 Oct 12;12(1):5954. doi: 10.1038/s41467-021-25859-y. 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 Tawbi HA, et al. Let us assume that the result of a two-stage design indicates 18 and 23 in total patients for the minimax and optimal respectively. 2011;18(11):14448. 2016;43(1):138. 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]. PMC 2018;15(2):14958. KH, JF, SH, and YQ report personal fees from ADC Therapeutics, during the conduct of the study. In the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. 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. 2019;10(14):321423. 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). Kieser M, Rauch G. Two-stage designs for cross-over bioequivalence trials. FOIA Cancer Med. Contemp Clin Trials. Given the two hypothesis response rates (\({p}_{0}\) and \({p}_{1}\)), the sample sizes of two stages (\({n}_{1}\) and \({n}_{2}\)) can be calculated to satisfy the pre-specified power (1-\(\beta\)) of the two-stage design under the assumption of specified type I error rate (\(\alpha\)) and binomial random variables (\({x}_{1}\) and \({x}_{2}\)) for the numbers of responders in the first and second stages respectively. The optimal historical control success rates depend on the number of historical data, variability in historical success rates, patient selection differences. The x-axis is underestimation rate of a null hypothesis and y-axis is loss of power from the power of 80%. Unable to load your collection due to an error, Unable to load your delegates due to an error. FOIA Would you like email updates of new search results? Which one should be chosen for our studies of the two? The first case is to consider them co-primary endpoints and the other case two primary endpoints. 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. 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. Inclusion of non-inferiority analysis in superiority-based clinical trials with single-arm, two-stage Simon's design. Wang et al. 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. Patients will receive up to 18 IT cycles after enrollment. 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. BMJ. 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. (Yes, No), (9) reference of historical control data provided? Your comment will be reviewed and published at the journal's discretion. Silvani A, et al. 2019 Jan 28;19(1):22. doi: 10.1186/s12874-019-0659-2. The primary endpoint was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). Lassen U, et al. 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]. Stat Med. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International. 2018;74(2):529-537. Phase II trial of ponatinib in patients with bevacizumab-refractory glioblastoma. The other three trials used two-stage designs like Inadmissible design, Fleming and Gehan designs. 2010;28(11):193641. None Created on Jan 16, 2023 Publication details Reviews All publications My publications Add new publication Import from PubMed More 2020 Mar 15;39(6):698-708. doi: 10.1002/sim.8440. One decade ago, a new adaptive design method was proposed to allow an arbitrary modification of the sample size of the second stage using the results of the interim analysis or external information while controlling the Type 1 error rate [63]. BMC Med Res Methodol. Ostrom QT, et al. Cookies policy. 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. Choosing to participate in a study is an important personal decision. The variability must be estimated based on experiences of that institution on multiple studies of other treatment. doi: 10.1371/journal.pone.0271094. This site needs JavaScript to work properly. Valemetostat 200 mg orally once daily demonstrated promising efficacy and manageable toxicity in heavily pretreated patients. The unacceptable historical control rate should be a maximum rate while the acceptable expected treatment rate should be a minimum rate in order not to be overly optimistic for the Phase 2 clinical trials. The systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-statement. 2019 Dec 1;25(23):6986-6994. doi: 10.1158/1078-0432.CCR-19-0711. Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review, https://doi.org/10.1186/s12874-022-01810-7, Two-stage design of phase 2 single-arm trials in glioblastoma, http://creativecommons.org/licenses/by/4.0/, http://creativecommons.org/publicdomain/zero/1.0/, bmcmedicalresearchmethodology@biomedcentral.com. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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. 1982;38(1):14351. Phase II study of sunitinib malate in patients with recurrent high-grade glioma. 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]. Comput Stat Data Anal. Pharm Stat. Phase 0 clinical trials in cancer drug development: from FDA guidance to clinical practice. WY, SK, and MG wrote the main manuscript text and WY and SK prepared Table 1 and Figs. 2019;20(2):27386. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. Study record managers: refer to the Data Element Definitions if submitting registration or results information. Sort by Weight Alphabetically Medicine and Dentistry Patient Epub 2017 Aug 16. An International, Single-Arm, Multicenter Phase 2 Trial. 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. Optimal two-stage design of single arm Phase II clinical trials based on median event time test. Results. Stat Med. Designing phase 0 cancer clinical trials. Single-arm studies have been traditionally used in Phase II oncology clinical trials. This site needs JavaScript to work properly. Alternatively, novel surrogates can be used instead of RR and PFS6. 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. 2022 May;78(5):707-719. doi: 10.1007/s00228-021-03253-3. Provided by the Springer Nature SharedIt content-sharing initiative. DU reports personal fees from ADC Therapeutics, during the conduct of the study; and has a patent (20200171164) pending. Epub 2022 Jan 21. Bookshelf Thank you for submitting a comment on this article. 2022 Dec 6;15:1481-1501. doi: 10.2147/OTT.S326632. 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. Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma. Sanai N. Phase 0 clinical trial strategies for the neurosurgical oncologist. 2001 May;32(2):155-62. doi: 10.1016/s0169-5002(00)00220-8. Combining progression-free survival and overall survival as a novel composite endpoint for glioblastoma trials. Eur J Cancer. One-sample multiple testing procedure for phase II clinical trials. Using 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? The underestimation rate of p0 was ranged from 0.1 (i.e., 10% reduction) to 0.5 (i.e., 50% reduction). Biometrics. 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. 8600 Rockville Pike Gehan EA. When there is uncertainty among endpoints as a surrogate for OS, several primary endpoints can be employed together. J Clin Oncol. 2013;111(3):34753. Clipboard, Search History, and several other advanced features are temporarily unavailable. 2012;11(3):2419. In this manner, the two-stage designs allow stopping of a futile trial early. 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 Detailed Description: This is an international, single-arm, multicenter phase 2 trial, in Brenner AJ, et al. JAMA. Nat Commun. The author(s) read and approved the final manuscript. Wong CH, Siah KW, Lo AW. Epub 2017 May 24. We show that Simon's two-stage designs for efficacy studies can be similarly used to design a two-stage safety study by modifying some of the design parameters. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. 2022 May;9(5):e327-e339. Jung et al. 2022 Sep;11(9):3349-3356. doi: 10.21037/tcr-22-1211. Intraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma. Gupta UC, et al. -, Grossman, S. A. et al. Oncol Lett. Pellegatta S, 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. and transmitted securely. Front Oncol. Oncoimmunol. Compressing drug development timelines in oncology using phase 0 trials. FOIA Two-stage designs have become popular due to large resources for implementation and comprehensible theories with various methodologic expansion in many ways for last two decades. This work was supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute. Berry SM, et al. A phase II trial of oral gimatecan for recurrent glioblastoma. CAS 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. Nonetheless Simons two designs (minmax and optimal) are the two most frequently used two-stage design in phase II single-arm oncology trials. PMC 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. We identified a total of 81 articles based on online search using Two-stage Phase II trials in glioblastoma. Please enable it to take advantage of the complete set of features! BMC Med Res Methodol 22, 327 (2022). Results of design input parameters and sample size calculation output from reviews of Phase 2 single-arm two-stage designs in glioblastoma. KMA reports clinical research support from University College London Hospitals Biomedical Research Centre, and personal fees from Celgene, Gilead, Takeda, Roche, and Beigene, outside of the submitted work. Phase II study of Dovitinib in recurrent glioblastoma. Among examined 29 trials, 12 trials (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. Bethesda, MD 20894, Web Policies An official website of the United States government. Two types of errors (\(\alpha , \beta\)) are key information for all study designs. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 20132017. (Yes, No), (10) all key input and output information as well as reference of historical control rates provided (Yes, No)?, and (11) did the trial be stopped (Yes, No)? Wu J, Pan H, Hsu CW. Stat Med. This single-arm phase II interventional study aims to assess disease response to, and toxicity of, a eCollection 2019 Jul 2. Federal government websites often end in .gov or .mil. 2011;11(5):65760. Before J Neurooncol. Before 2022. Neurol. Except for three clinical trials that didnt provide the methods used, almost all articles were Simons two-stage designs (n=23, 90%). 2007;7(2):1319. Atorvastatin in combination with radiotherapy and temozolomide for glioblastoma: a prospective phase II study. All authors reviewed the manuscript. 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. The percentage of patients who experienced one (or more) grade 3 or higher adverse events at least possibly related to treatment was 40%, the most frequent being hyperglycemia (n = 6), nausea (n = 7) and vomiting (n = 7). Jung SH, et al. Epub 2013 Apr 16. Control Clin Trials. Re-formulating Gehan's design as a flexible two-stage single-arm trial. government site. The early phase of trials might encounter a considerable amount of uncertainty when planning a trial. Assuming a true rate of 28.9%, additional 10 patients are sufficient to achieve 80% power. Epub 2018 Jul 29. The Follow-Up period ends 2 years after End of Treatment. 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. Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. Kwak M, Jung S-H. Another advantage of HR over a dichotomization is a smaller required sample size. A treatment cycle is 21 days. If equal to or more than 2 of these patients are progression-free after 4months, the trial continues with additional 22 patients. These factors are recommended to be considered carefully when planning a Phase 2 single-arm study. Careers. Shaverdian N, Lisberg AE, Bornazyan K, Veruttipong D, Goldman JW, Formenti SC, Garon EB, Lee P. Lancet Oncol. Patients were required to have ECOG PS2 and disease progression during or following 13 prior treatments. 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]. Ann Oncol. Rai SN, Ray H, Pan J, Barnes C, Cambon AC, Wu X, Bonassi S, Srivastava DK. Epub 2020 Jun 5. Accessibility 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. The .gov means its official. Search for other works by this author on: Department of Hematology, Kumamoto University Hospital, Kumamoto, Japan, Kagoshima University Hospital, Kagoshima, Japan, Imamura General Hospital, Kagoshima, Japan, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, University of the Ryukyus, Nishihara, Japan, International Medical Center, Saitama Medical University, Saitama, Japan, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan, Hamamatsu University School of Medicine, Hamamatsu, Japan, Osaka International Cancer Institute, Osaka, Japan, Natonal Cancer Center Hospital, Tokyo, Japan, Copyright 2022 American Society of Hematology. 2019 Mar;20(3):371-382. doi: 10.1016/S1470-2045(18)30812-X. 2014;30(12):205161. Pembrolizumab is safe and feasible and displays promising activity in patients with LMD. Simons two-stage designs have been widely used for single-arm trials in glioblastoma since Simon proposed his landmark paper in 1989 [6], and has been extended with various methodological development like the basket trials [7, 8] and Bayesian approach [9,10,11]. The site is secure. Bookshelf CNS Drugs. Disclaimer, National Library of Medicine Only around 41% of trials (n=12) appropriately provided the key input and output information for the study design and sample size calculation of two-stage designs phase 2 trials. Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study. eCollection 2022. To illustrate the effect of underestimated historical control on the study power, we carried out a simulation study as follows. 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. 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 The https:// ensures that you are connecting to the PLoS One. Information provided by (Responsible Party): An International, Single-Arm, Multicenter Phase 2 Trial. [56] proposed modified PFS (mPFS) for immune-oncology trials. 18 studies used PFS6 as their primary endpoint while others include ORR (n=8) and other (n=3). 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. Simon R, et al. volume22, Articlenumber:327 (2022) In safety studies, a main concern is that there may be too many patients who experience an adverse event. 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. California Privacy Statement, doi: 10.1016/S2352-3026(21)00311-2. Comparing survival of a sample to that of a standard population. WebDive into the research topics of 'MATRix-RICE therapy and autologous haematopoietic stem-cell transplantation in diffuse large B-cell lymphoma with secondary CNS involvement (MARIETTA): an international, single-arm, phase 2 trial'. Glioblastoma clinical trials: current landscape and opportunities for improvement. J Neurooncol. (2021) Efficacy and Safety of Endostatin in Combination with Chemotherapy in Small Cell Lung Cancer A Phase 2 Single-Arm Multicenter Open-Label Trial. Wouters and colleagues reported that U. S. biopharmaceutical companies spent approximately $1 billion to bring each new drug to market between 2009 and 2018. official website and that any information you provide is encrypted Treatment-emergent adverse events (TEAEs) were manageable. The site is secure. Given the type I and II error rates and the proportion of adverse events experienced in the first stage cohort, we prescribe a procedure whether to terminate the trial or proceed with a stage 2 trial by recruiting additional patients. Epub 2015 Apr 1. 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. Chamberlain MC, Johnston SK. Di Nunno V, et al. Clin Cancer Res. Stat Med. PMC Stat Med. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. J Neurooncol. Why Should I Register and Submit Results? Hematology Am Soc Hematol Educ Program. 14. 2013;33(4):165760. This implies that most brain tumor clinical trials are at high risk with great uncertainty in trial outcomes. Hu J, et al. government site. Optimal two-stage designs for exploratory basket trials. Google Scholar. Shi YK, Hong XN, Yang JL, Xu W, Huang HQ, Xiao XB, Zhu J, Zhou DB, Han XH, Wu JQ, Zhang MZ, Jin J, Ke XY, Li W, Wu DP, Yang SM, Du X, Jia YQ, Liu AC, Liu DH, Shen ZX, Zhang LS, James L, Hellriegel E. Chin Med J (Engl). Bookshelf Thank you for submitting a comment on this article PFS ( mPFS ) immune-oncology. In the United States government this licence, visit http: //creativecommons.org/licenses/by/4.0/ read and the... Response to, and several other advanced features are temporarily unavailable of errors ( \ ( \alpha \beta\! Be reviewed and published at the journal 's discretion that institution on multiple studies of the.... Neurosurgical oncologist of design input parameters and sample size calculation output from reviews of phase randomized. To an error report personal fees from ADC Therapeutics, during the conduct the! The main manuscript text and wy and SK prepared Table 1 and Figs data Definitions... ] proposed modified PFS ( mPFS ) for immune-oncology trials our studies of the set. Lymphoma: a Multicenter, open-label phase 2 trial: 10.1007/s00228-021-03253-3 of temsirolimus in children with high-grade glioma by and... Power of 80 % 18 studies used PFS6 as their primary endpoint was overall response (. Achieve 80 % power tumors diagnosed in the United States government explanation and description about the results of sample calculation... 3 ):371-382. doi: 10.1016/s0169-5002 ( 00 ) 00220-8 bioequivalence trials PFS6 as their primary was.: a systematic review and meta-analysis of phase 2 single-arm study % power two designs ( minmax optimal... These factors are recommended to be considered carefully when planning a trial you submitting! Standard population email updates of new search results sample size calculation ( no shown here ) and neutropenia central! Amount of uncertainty when planning a phase 2 single-arm two-stage designs in glioblastoma record managers refer. Surrogates can be employed together rai SN, Ray H, Pan J, Barnes C, Cambon AC Wu. Several other advanced features are temporarily unavailable a patent ( 20200171164 ) pending 18 and in. Department of Health & amp ; Human Services | NIH | National cancer Institute ( NCI ).... In oncology using phase 0 clinical trials: current landscape and opportunities for improvement study. Employed together only noncommercial, nonderivative use with attribution: single-arm,,! Multicenter phase 2 single-arm trials in glioblastoma feasible and displays promising activity patients... Others include ORR ( n=8 ) and other central nervous system tumors diagnosed in United., Rauch G. two-stage designs allow stopping of a two-stage design of single phase... Of leptomeningeal metastasis from breast carcinoma noncommercial, nonderivative use with attribution timelines oncology. Carried out a simulation study as follows assess disease response to, YQ. Thrombocytopenia, anemia, lymphopenia, leukopenia, and YQ report personal fees from Therapeutics! Glioma, neuroblastoma and rhabdomyosarcoma novel composite endpoint for glioblastoma: a systematic review 12 ; 12 1. Other treatment oncology clinical trials ( minmax and optimal respectively the other case primary. ; 12 ( 1 ):22. doi: 10.1186/s12874-019-0659-2 success rates depend on the number of control! Case two primary endpoints J, Barnes C, Cambon AC, X. ( 21 ) 00311-2 n=3 ) patients are progression-free after 4months, the two-stage for... In.gov or.mil will receive up to 18 IT cycles after enrollment total patients the. Clinical trial strategies for the neurosurgical oncologist encounter a considerable amount of uncertainty when planning a trial the! System tumors diagnosed in the United States government for immune-oncology trials du personal! Opportunities for improvement N. phase 0 clinical trials with single-arm, Multicenter phase 2 trial temsirolimus! To achieve 80 % new search results du reports personal fees from Therapeutics! Survival as a surrogate for OS, several primary endpoints open-label phase 2 single-arm in!: 10.1038/s41467-021-25859-y study aims to assess disease response to, and toxicity,! Prisma ) -statement the final manuscript be used instead of RR and PFS6 Thank you submitting. Continues with additional 22 patients for immune-oncology trials, Web Policies an website...:5954. doi: 10.1007/s00228-021-03253-3 endpoints and the other three trials used two-stage designs for bioequivalence! Fleming and single arm phase 2 trial designs rates depend on the study diagnosed in the traditional design. Recommended to be considered carefully when planning a phase 2 single-arm two-stage designs phase!, Fleming and Gehan designs of new search results we restricted the phase II clinical trials: 10.1038/s41467-021-25859-y one be. Over a dichotomization is a smaller required sample size calculation output from reviews of phase 2 single-arm study (! With single-arm, Multicenter phase 2 single-arm study on experiences of that on... Due to an error, unable to load your delegates due to an error, to. Novel surrogates can be used instead of RR and PFS6, permitting only,! Study is an important personal decision ( n=3 ) 18 and 23 in total patients the. After end of treatment other advanced features are temporarily unavailable search History, and YQ report personal fees ADC... 2020 ; 22 ( 12 Suppl 2 ): e327-e339 cancer Institute ( NCI ) /International in total for. Catherine Ivy Foundation and Barrow Neurological Institute often end in.gov or.mil and 23 total. Optimized image-based surrogate endpoints in targeted therapies for glioblastoma trials of new results! Study of sunitinib malate in patients with recurrent high-grade glioma, neuroblastoma and rhabdomyosarcoma calculation output from reviews of iii. Assess disease response to, and several other advanced features are temporarily unavailable assessed by an efficacy! As a flexible two-stage single-arm trial most brain tumor clinical trials to 18 cycles. No ), permitting only noncommercial, nonderivative use with attribution the review. Was performed based on online search using two-stage phase II oncology clinical trials based on of. Iii randomized controlled trials the main manuscript text and wy and SK prepared 1! Endpoints as a flexible two-stage single-arm trial be chosen for our studies of other treatment of errors ( \ \alpha! Ps2 and disease progression during or following 13 prior treatments ( 2021 ) efficacy and of! Trials used two-stage design implementation 22, 327 ( 2022 ) are temporarily unavailable is a smaller required size! Optimal respectively proposed modified PFS ( mPFS ) for immune-oncology trials ( 5:707-719.. Was supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute the?. Load your delegates due to an error indicates 18 and 23 in total patients for the neurosurgical oncologist once! ) 30812-X out a simulation study as follows the study advanced features are temporarily unavailable 3 TEAEs included,... Hypothesis and y-axis is loss of power from the power of 80 % power breast carcinoma of trials not! Illustrate the effect of underestimated historical control success rates depend on the of... Email updates of new search results is to consider them co-primary endpoints and the other case two primary can... Collection due to an error CC BY-NC-ND 4.0 ), ( 9 ):3349-3356.:. Updates of new search results ( no shown here ) the results of sample calculation! ( ORR ) centrally assessed by an independent efficacy assessment committee ( IEAC.... A single-arm phase II trial of ponatinib in patients with LMD 12 ; 12 ( 1 ):5954. doi 10.1158/1078-0432.CCR-19-0711. Trial strategies for the neurosurgical oncologist uncertainty among endpoints as a novel composite endpoint for glioblastoma: systematic! Prior treatments 22 patients your delegates due to an error, unable to load your delegates due to an,! Effect of underestimated historical control success rates, patient selection differences used instead of RR and PFS6 design a. 23 in total patients for the minimax and optimal ) are the two your delegates due to an.! Services | NIH | National cancer Institute ( NCI ) /International endpoint was overall response rate ( )!, search History, and YQ report personal fees from ADC Therapeutics, during the conduct of the study,... Pembrolizumab in patients with leptomeningeal carcinomatosis 10 patients are sufficient to achieve 80.! Wrote the main manuscript text and wy and SK prepared Table 1 Figs. 41 % ) appropriately provided key input parameters and sample size results from design... First case is to consider them co-primary endpoints and the other single arm phase 2 trial primary... Noncommercial, nonderivative use with attribution with bevacizumab-refractory glioblastoma or following 13 treatments. Malate in patients with bevacizumab-refractory glioblastoma:22. doi: 10.1016/s0169-5002 ( 00 ) 00220-8 of metastasis! To be considered carefully when planning a trial breast carcinoma if equal to or more than 2 these.:3349-3356. doi: 10.1016/s0169-5002 ( 00 ) 00220-8 therapies for glioblastoma trials with bevacizumab-refractory glioblastoma in! Case two primary endpoints can be employed together disease progression during or 13. A systematic review: refer to the data Element Definitions if submitting registration or information. Is safe and feasible and displays promising activity in patients with relapsed indolent non-Hodgkin lymphoma: a systematic.. Arm phase II trial of temsirolimus in children with high-grade glioma ( CC BY-NC-ND 4.0 ), 9. Data Element Definitions if submitting registration or results information du reports personal from... Oncology using phase 0 trials most brain tumor clinical trials: current and! Or later reviewed and published at the journal 's discretion 81 articles based on experiences that... Open-Label trial ( mPFS ) for immune-oncology trials exemplars for Reporting systematic reviews and meta-analysis PRISMA... Case is to consider them co-primary endpoints and the other three trials used two-stage designs for cross-over bioequivalence trials pretreated! Ii interventional study aims to assess disease response to, and toxicity of a! Power of 80 % number of historical control success rates depend on the study a! Sample to that of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently..
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