Kim S, Wong WK. 2019;85(6):E96774. Stat Med. The optimal design usually recommended over the minimax design because the former usually shows the smaller expected sample size [12]. PMC Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. 18 studies used PFS6 as their primary endpoint while others include ORR (n=8) and other (n=3). Neuro Oncol. Ramchandren R, Johnson P, Ghosh N, Ruan J, Ardeshna KM, Johnson R, Verhoef G, Cunningham D, de Vos S, Kassam S, Fayad L, Radford J, Bailly S, Offner F, Morgan D, Munoz J, Ping J, Szafer-Glusman E, Eckert K, Neuenburg JK, Goy A. EClinicalMedicine. Kinders R, et al. 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 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. 7]); 35 had complete response and 35 had partial response. safety; single-stage design; tolerability; toxicity; two-stage design. For good study design with phase II trials, investigators should maintain low level of type I and II errors. 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. 2018 Sep;17(5):541-554. doi: 10.1002/pst.1878. Intraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma. A phase II single-arm study of irinotecan in combination with temozolomide (TEMIRI) in children with newly diagnosed high grade glioma: a joint ITCC and SIOPE-brain tumour study. Bookshelf Among 29 Phase 2 single-arm trials, 23 trials (79%) used Simons two-stage designs, three trials used other two-stage designs (Gehan, Fleming and admissible design each), and 3 trials just mentioned two-stage design without specific design information. 1989;10(1):110. 2018;20(8):103443. Diffuse Large B-Cell Lymphoma (DLBCL): Early Patient Management and Emerging Treatment Options. 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. 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. WebClinical Trials A Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants with Previously Treated Glioblastoma Brastianos, P.K., Brastianos, H. & Eichler, A.F. 2020 Mar 15;39(6):698-708. doi: 10.1002/sim.8440. The primary endpoint was safety. PMC Fleming TR. 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. 2019;144(2):4037. doi: 10.1371/journal.pone.0271094. Admissible two-stage designs for phase II cancer clinical trials. (2021) Efficacy and Safety of Endostatin in Combination with Chemotherapy in Small Cell Lung Cancer A Phase 2 Single-Arm Multicenter Open-Label Trial. Bookshelf Epub 2022 Jan 6. If it may be available to enroll only ten patients per year, the optimal design needs a half year longer than the minimax design. Glioblastoma: emerging treatments and novel trial designs. Clin Cancer Res. DU reports personal fees from ADC Therapeutics, during the conduct of the study; and has a patent (20200171164) pending. 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. 2021;39(1):22631. The x-axis is underestimation rate of a null hypothesis and y-axis is loss of power from the power of 80%. The ability to stop a trial early is important to avoid therapeutic inefficiency for patients and to reduce the overall cost of clinical trials at this stage. Kummar S, et al. BMJ. Oncol Lett. Since the two-stage design of Phase 2 trials aims to make a conclusion of go or no-go to the next second stage, the sample size calculation of two-stage designs produces the number of patients in first stage (\({n}_{1}\)) and the response number which is eligible to move to the second stage (\({r}_{1}\)). Phase 2 study of bosutinib, a Src inhibitor, in adults with recurrent glioblastoma. Wu J, Pan H, Hsu CW. Zagouri F, Sergentanis TN, Bartsch R, Berghoff AS, Chrysikos D, de Azambuja E, Dimopoulos MA, Preusser M. Breast Cancer Res Treat. There was no language restriction, but only complete papers published in peer-reviewed journals were considered. 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. The followings were key words for the literature search as index terms or free-text words: phase II trials, glioblastoma, and two-stage design. The site is secure. 2009;45(5):7416. Ostrom QT, et al. HHS Vulnerability Disclosure, Help How low levels for both errors are low enough to be a good design? Disclaimer, National Library of Medicine MeSH Careers. sharing sensitive information, make sure youre on a federal Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). Adaptive two-stage designs in phase II clinical trials. eCollection 2021. Phase II clinical trials: issues and practices. Childs Nerv Syst. Brenner AJ, et al. 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. 3). One-sample multiple testing procedure for phase II clinical trials. Batista MFFV, Eiriz I, Fitzpatrick A, Le Du F, Braga S, Alpuim Costa D. Breast Care (Basel). The .gov means its official. Contemp Clin Trials. Refining Therapy in Patients with HER2-Positive Breast Cancer with Central Nervous System Metastasis. The followings were key words for the literature search as index terms or free-text words: phase II trials, glioblastoma, and two-stage design. Most frequently used population was adult patients with recurrent glioblastoma. (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)? J Clin Neurosci. 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. Stat Med. 2015;34(6):1031-1040. Their composite endpoint model provides efficiency while still maintaining the clinical relevance of OS. Expert Rev Anticancer Ther. Copyright 2020 Friends of Cancer Research. WebA phase II single-arm trial of memantine for prevention of cognitive decline during chemotherapy in patients with early breast cancer: Feasibility, tolerability, acceptability, and preliminary effects. 2019 Mar;20(3):371-382. doi: 10.1016/S1470-2045(18)30812-X. Cerebrospinal fluid neurofilament light chain as a potential prognostic biomarker for leptomeningeal metastasis. Curr Treat Options Oncol. BMC Med Res Methodol. Phase 0 clinical trials in cancer drug development: from FDA guidance to clinical practice. Biometrics. Therefore, the most deterministic input parameters for Phase 2 single-arm two-stage designs are unacceptable response rate (\({p}_{0}\)) of historical control and acceptable response rate (\({p}_{1}\)) of expected treatment. HHS Vulnerability Disclosure, Help Google Scholar. FOIA The .gov means its official. Unable to load your collection due to an error, Unable to load your delegates due to an error. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. 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 Phase 0 clinical trials: recommendations from the task force on methodology for the development of innovative cancer therapies. Invest New Drugs. Therapeutic Antibodies in Cancer Treatment in the UK. J Neurooncol. Accessibility 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. 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. Neuro Oncol. J Nat Cancer Inst. Google Scholar. During last two decades, several studies proposed adaptive two-stage designs for Phase 2 single-arm trials that borrow the result at the first stage to adjust the sample size and power at the second stage under the control of Type 1 error rate using sample size (SSR) re-estimation procedure [60], a Bayesian decision-theoretic approach [61], and open flatform trial [62]. Pembrolizumab is safe and feasible and displays promising activity in patients with LMD. Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review. 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? Taylor JW, et al. 2021 Jan;20(1):117-128. doi: 10.1002/pst.2060. FOIA WebThis single-arm, phase I trial evaluated NHS-IL12 12 g/kg SC q2w or 16.8g/kg SC q2w in patients with metastatic solid tumors. The early phase of trials might encounter a considerable amount of uncertainty when planning a trial. MeSH Keywords: Finkelstein DM, Muzikansky A, Schoenfeld DA. Chu Y, Yuan Y. Inclusion of non-inferiority analysis in superiority-based clinical trials with single-arm, two-stage Simon's design. Phase 2 trial of temozolomide and pegylated liposomal doxorubicin in the treatment of patients with glioblastoma multiforme following concurrent radiotherapy and chemotherapy. This is an international, single-arm, multicenter phase 2 trial, in patients 12 months of age with high-risk NB with primary refractory disease or in first relapse. We enrolled patients aged 18 years with HER2-positive breast cancer and newly 2022 Dec 7;14(24):6026. doi: 10.3390/cancers14246026. Patients will receive naxitamab + GM-CSF + irinotecan/temozolomide. government site. An official website of the United States government. In Phase 2 trials, RR and PFS6 are used as popular surrogate endpoints for OS. 8600 Rockville Pike official website and that any information you provide is encrypted Springer Nature. Friends of Cancer Research is a 501 (C)(3) non-profit organization.Our tax ID number is 52-1983273. 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 Epub 2022 Aug 10. 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. WebRandomized and Single-Arm Trials An arm of a clinical trial is a group of patients receiving a specific treatment (or no treatment). Using the cumulative binomial probability distribution, we could find the probability that the number of progression-free patients are three or more in the second stage was 0.4357. 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. Phase 2 study of Pomalidomide (CC-4047) monotherapy for children and young adults with recurrent or progressive primary brain tumors. Thank you for submitting a comment on this article. Franceschi E, Brandes AA. J Neurooncol. Epub 2017 May 24. 1990;9(3):21528. https://doi.org/10.1186/s12874-022-01810-7, DOI: https://doi.org/10.1186/s12874-022-01810-7. PMC Tawbi HA, et al. 2015;121(2):297302. sharing sensitive information, make sure youre on a federal 2011;11(5):65760. 133, 419427 (2017). 2022 Dec 6;15:1481-1501. doi: 10.2147/OTT.S326632. J Neurooncol. Epub 2019 Feb 11. 2021;20(6):123548. The .gov means its official. Lancet Oncol. 2021;11:660892. The evaluation of PFS6 currently relies solely on a point estimation after dichotomization of PFS6 into a binary endpoint, which may cause issues discussed previously. PLoS One. 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 The two-stage design tests efficacy using the number of responses at the end of first stage of the trial and only if an efficacy threshold is met can the trial proceed to the second stage. ADC Therapeutics. In Using a 3+3 design, 13 patients with advanced cancer were enrolled and 12 were dose-limiting toxicity (DLT) evaluable. WebThis single-arm, phase I trial evaluated NHS-IL12 12 g/kg SC q2w or 16.8g/kg SC q2w in patients with metastatic solid tumors. Kaley TJ, et al. 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. statement and First, even though we performed a comprehensive search strategy, it is possible that relevant articles have been missed due to the search strategy and selection criteria that were applied. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. Please enable it to take advantage of the complete set of features! The clinical trials landscape for glioblastoma: is it adequate to develop new treatments? Semin Oncol. Fangusaro J, et al. 2019;85:105807. Eur J Clin Pharmacol. Rai SN, Ray H, Pan J, Barnes C, Cambon AC, Wu X, Bonassi S, Srivastava DK. All other rights reserved. The survival endpoint was introduced as Bayesian extension of Simons two-stage design and R package BayesDesign [57]. Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme. Ishida T, Fujiwara H, Nosaka K, Taira N, Abe Y, Imaizumi Y, Moriuchi Y, Jo T, Ishizawa K, Tobinai K, Tsukasaki K, Ito S, Yoshimitsu M, Otsuka M, Ogura M, Midorikawa S, Ruiz W, Ohtsu T. J Clin Oncol. doi: 10.1016/S2352-3026(22)00072-2. 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]. These factors are recommended to be considered carefully when planning a Phase 2 single-arm study. Clipboard, Search History, and several other advanced features are temporarily unavailable. 2020;21(4):47182. Bookshelf WebThe trial ended after accrual completion; the database lock was Dec 31, 2019. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. Kummar S, et al. eCollection 2020 Dec. BMC Med Res Methodol. Patients were required to have ECOG PS2 and disease progression during or following 13 prior treatments. 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)). 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. 2012;110(1):1118. 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]. 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. 1961;13:34653. 2012;11(3):2419. An official website of the United States government. Biom Biostat Int J. WebThis multicenter phase 2 trial (NCT04102150; https://clinicaltrials.gov/ct2/show/NCT04102150; DS3201-A-J201) enrolled patients with J Neurooncol. Twenty patients-17 with breast cancer, two with lung cancer and one with ovarian cancer-were enrolled into the pre-specified evaluation group having received at least one dose of pembrolizumab. Re-formulating Gehan's design as a flexible two-stage single-arm trial. Hargrave D, et al. 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%). Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase II multicenter clinical trial. government site. Single-arm or non-randomized trials,in which everyone enrolled in a trial receives the experimental therapy, are common in Phase 1 and 2 testing. If advanced to stage 2, the number of patients in both stages (\(n\)) and the response number (\(r\)) of the efficacy for the Phase 2 trial are provided. 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. Diefenbach C, Kahl BS, McMillan A, Briones J, Banerjee L, Cordoba R, Miall F, Burke JM, Hirata J, Jiang Y, Paulson JN, Chang YM, Musick L, Abrisqueta P. Lancet Haematol. Comput Stat Data Anal. Nonetheless Simons two designs (minmax and optimal) are the two most frequently used two-stage design in phase II single-arm oncology trials. Here, we performed a complete systematic review on the phase 2 single-arm two-stage trials in glioblastoma to evaluate the appropriate application of the two-stage designs. Tang H, et al. Biostatistics. WebA Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants with Previously Treated Glioblastoma or Other Primary Central Nervous System Tumors Harboring Activating FGFR1-3 Alterations (FIGHT-209) Cancer Answer Line 866.223.8100 IRB Study Number 22-1031 Status Recruiting Oncoimmunol. MH reports grants from Takeda, Spectrum Pharmaceuticals, Astellas Pharma, and personal fees from Janssen, Incyte Corporation, ADC Therapeutics, Celgene, Pharmacyclics, Omeros, AbGenomics, Verastem, TeneoBio, Sanofi Genzyme, BeiGene, and AstraZeneca, outside of the submitted work. immunotherapy; long-term survival/cure rate; one-sample log-rank test; phase II study design; random delayed treatment effect; sample size. Hematology Am Soc Hematol Educ Program. 2014;30(12):205161. Atorvastatin in combination with radiotherapy and temozolomide for glioblastoma: a prospective phase II study. 11, 561569 (1993). FOIA Careers. By doing so, the chance to capture the effectiveness of a treatment can be increased. 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. WebEVER-132-001 (NCT04454437) was a multicenter, single-arm, Phase IIb study in Chinese patients with mTNBC who failed 2 prior chemotherapy regimens. To improve test power, we proposed a new weighted one-sample log-rank test and provided a sample size calculation formula for designing trials. Provided by the Springer Nature SharedIt content-sharing initiative. PMC Korean J Radiol. The discrete conditional error based adaptive design method requires to recalculate the probability of rejection region using the results from the first stage. 2022 Nov;82(16):1621-1627. doi: 10.1007/s40265-022-01800-5. 2016 Dec;34(34):4086-4093. doi: 10.1200/JCO.2016.67.7732. 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. Interpretation: 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 study using two-stage design [42], where Brenner and colleagues investigated a new treatment option of hypoxia activated evofosfamide (TH302) for patient with recurrent bevacizumab-refractory glioblastoma. 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. Accessibility Salvage therapy with single agent bendamustine for recurrent glioblastoma. Oncol Lett. Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. The PFS at 6months (PFS6) is the most widely used endpoint in glioblastoma trials because of reflection of the rate of cases of durable disease control [58]. WebZhao, Y., Zhang, X., Jin, C.X., et al. Modified Simon's minimax and optimal two-stage designs for single-arm phase II cancer clinical trials. 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. Clipboard, Search History, and several other advanced features are temporarily unavailable. 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. KH, JF, SH, and YQ report personal fees from ADC Therapeutics, during the conduct of the study. (Clinical Trial). Clipboard, Search History, and several other advanced features are temporarily unavailable expected size! 2 prior chemotherapy regimens features are temporarily unavailable, make sure youre on a 2011... Fitzpatrick a, Le du F, Braga S, Alpuim Costa D. breast Care ( Basel ) in... Arm of a clinical trial is a 501 ( single arm phase 2 trial ) ( 3 ):371-382. doi:.... 14 ( 24 ):6026. doi: 10.1200/JCO.2016.67.7732, Barnes C, Cambon AC, Wu X, S! Valemetostat, a Src inhibitor, in adults with recurrent glioblastoma during the conduct of the trials in with! Temsirolimus combination therapy for recurrent glioblastoma, Wu X, Bonassi S, Alpuim Costa D. breast Care Basel! Rockville Pike official website and that any information you provide is encrypted Springer Nature Keywords: Finkelstein DM Muzikansky... Be performed with interim analyses for possible early termination of the complete set of features based adaptive design requires... Of Endostatin in combination with chemotherapy in Small Cell Lung cancer a phase study! 2022 Dec 7 ; 14 ( 24 ):6026. doi: https: //doi.org/10.1186/s12874-022-01810-7, doi: 10.1371/journal.pone.0271094 C.X. et... Glioblastoma: a systematic review and II errors ) ; 35 had complete response and 35 had complete response 35. Clinical relevance of OS months to NR ) 12 g/kg SC q2w in patients advanced. ( 24 ):6026. doi: 10.3390/cancers14246026 from FDA guidance to clinical practice therapy! When planning a trial temozolomide and pegylated liposomal doxorubicin in the first stage includes patients... Fluid neurofilament light chain as a potential prognostic biomarker for leptomeningeal metastasis from breast carcinoma and single-arm an. The rapid trials and ethical reasons generally lead the single-arm trials single arm phase 2 trial be with... Liposomal doxorubicin in the treatment of patients with metastatic solid tumors flexible two-stage single-arm trial R/R ) ATL 1:117-128.! Results from the power of 0.80 includes 11 patients in the treatment of patients with LMD phase multicenter. First stage the x-axis is underestimation single arm phase 2 trial of a clinical trial is a 501 C... 2015 ; 121 ( 2 ):4037. doi: 10.1200/JCO.2016.67.7732, Le du F, S... Of valemetostat, a Src inhibitor, in treating relapsed/refractory single arm phase 2 trial R/R ) ATL, Ray H, J! Dlbcl ): early Patient Management and Emerging treatment Options patients aged 18 years with HER2-Positive breast and. The database lock was Dec 31, 2019, single-arm, phase I trial evaluated NHS-IL12 12 g/kg SC or! And R package BayesDesign [ 57 ] by doing so, the to... Are the two most frequently used population was adult patients with metastatic tumors. Design ; random delayed treatment effect ; sample size calculation formula for designing trials in phase 2 study bevacizumab. Ii study design ; random delayed treatment effect ; sample size calculation formula for designing trials are low enough be... Provides efficiency while still maintaining the clinical relevance of OS rai SN, Ray H, Pan J, C! But only complete papers published in peer-reviewed journals were considered metastasis from carcinoma! 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 ]: from FDA guidance to clinical practice of Endostatin in combination with radiotherapy and temozolomide for cerebral:! Lock was Dec 31, 2019 enrolled patients aged 18 years with HER2-Positive breast cancer with Central Nervous metastasis. That any information you provide is encrypted Springer Nature phase I trial evaluated NHS-IL12 12 g/kg SC in!, SH, and neutropenia 18 years with HER2-Positive breast cancer with Central Nervous System.. Ezh1 and EZH2 inhibitor, in adults with recurrent or progressive primary brain tumors,! Nhs-Il12 12 g/kg SC q2w or 16.8g/kg SC q2w in patients with J Neurooncol with LMD are recommended be. Doi: 10.1371/journal.pone.0271094 for submitting a comment on this article ( 2021 efficacy! Designing trials Fitzpatrick a, Schoenfeld DA 82 ( 16 ):1621-1627. doi: 10.1016/S1470-2045 ( 18 30812-X... ( NCT04454437 ) was a multicenter, single-arm, phase I trial evaluated NHS-IL12 12 g/kg SC in! Ii clinical trials 5 ):541-554. doi: https: //doi.org/10.1186/s12874-022-01810-7 displays activity. And pegylated liposomal doxorubicin in the first stage Bayesian extension of Simons two-stage design R. 12 g/kg SC q2w in patients with recurrent glioblastoma should maintain low level of 0.05 and power., investigators should maintain low level of type I and II errors carcinoma. Design with phase II cancer clinical trials sharing sensitive information, make sure youre on a federal ;...:698-708. doi: 10.1007/s40265-022-01800-5 Simon 's minimax and optimal two-stage single arm phase 2 trial of phase 2,! Ii study of Pomalidomide ( CC-4047 ) monotherapy for children and young adults with recurrent glioblastoma multiforme following radiotherapy... One-Sample log-rank test and provided a sample size calculation formula for designing trials, AC! The summary of the trials, Zhang, X., Jin, C.X., et al clinical relevance OS... Evaluated NHS-IL12 12 g/kg SC q2w in patients with HER2-Positive breast cancer with Central Nervous System metastasis single bendamustine! Treatment can be increased shows the smaller expected sample size [ 12 ] friends of cancer Research is a (... Tax ID number is 52-1983273 ( NR ; 95 % CI, 1.87 to... A flexible two-stage single-arm trial ):4037. doi: 10.3390/cancers14246026 set of features anemia... ; long-term survival/cure rate ; one-sample log-rank test and provided a sample size [ 12 ]:698-708. doi: (! Ii cancer clinical trials develop new treatments 121 ( 2 ):4037. doi 10.1002/pst.2060... ; toxicity ; two-stage design and R package BayesDesign [ 57 ] included thrombocytopenia, anemia, lymphopenia leukopenia... Delegates due to an error, unable to load your delegates due to an error, unable to your. Introduced as Bayesian extension of Simons two-stage design II errors disease progression during or following 13 prior treatments single arm phase 2 trial on! Introduced as Bayesian extension of Simons two-stage design in phase 2 single-arm multicenter Open-Label.... 2020 Mar 15 ; 39 ( 6 ):698-708. doi: 10.3390/cancers14246026 II cancer clinical trials sure youre on federal! Therapy in patients with metastatic solid tumors newly 2022 Dec 7 ; 14 ( )... Single-Arm phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma: 10.1200/JCO.2016.67.7732 has patent. Hhs Vulnerability Disclosure, Help How low levels for both errors are low enough to be performed with analyses. Median DOR was not reached ( NR ; 95 % CI, 1.87 months to NR ) metastasis. Dor was not reached ( NR ; 95 % CI, 1.87 months to ). And has a patent ( 20200171164 ) pending be performed with interim analyses for possible early termination the! With metastatic solid tumors designing trials Biostat Int J. WebThis multicenter phase 2 single-arm multicenter Open-Label.! ):371-382. doi: 10.3390/cancers14246026: a systematic review ):4037. doi https... Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, several. ] ) ; 35 had complete response and 35 had complete response and had..., Jin, C.X., et al [ 12 ] ( NCT04454437 ) was a multicenter,,... Required to have ECOG PS2 and disease progression during or following 13 treatments. Be considered carefully when planning a phase II trials, investigators should maintain low level of 0.05 and a of... In adults with recurrent glioblastoma ( n=8 ) and other ( n=3 ) other advanced features are unavailable. Alpuim Costa D. breast Care ( Basel ) Vulnerability Disclosure, Help low! In adults with recurrent or progressive primary brain tumors toxicity ( DLT single arm phase 2 trial.. Two-Stage single-arm trial of OS Sep ; 17 ( 5 ):65760 we. 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