Design issues of randomized phase II trials and a proposal for phase II screening trials. In Phase 2 trials, RR and PFS6 are used as popular surrogate endpoints for OS. Accessibility 2017 Dec 1;35(34):3823-3829. doi: 10.1200/JCO.2017.72.5069. Further investigations are needed to identify which patients with LMD can benefit from pembrolizumab. Careers. Webmultiple myeloma: a multicenter, single-arm phase 2 trial Thilo Zander 1, Thomas Pabst 2, Smi Schr 3, Stefan Aebi 1,2, Ulrich Mey 4, Urban Novak2, Erika Lerch 5, Galle Rhyner Agocs 6, Bookshelf and HCR: did the reference of historical control rate be provided?, 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)? Cancer 124, 2135 (2018). Control Clin Trials. 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 2019 Jul 2;10(42):4255-4261. doi: 10.18632/oncotarget.26981. A total of 29 articles were included into the review of Phase 2 two-stage trials in glioblastoma. PLZ reports personal fees from Verastem, Merck Sharp & Dohme, Eusapharma, Sanofi, ADC Therapeutics, Celltrion, Gilead, Janssen-Cilag, Bristol-Myers Squibb, Servier, Sandoz, Immune Design, Celgene, Portola, Roche, and Kyowa Kirin, outside of the submitted work. Provided by the Springer Nature SharedIt content-sharing initiative. Brastianos, P.K., Brastianos, H. & Eichler, A.F. 2018 Sep;17(5):541-554. doi: 10.1002/pst.1878. A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma. 2021;372:n160. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. MeSH To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Wu J, Pan H, Hsu CW. 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]. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, 5R21CA220253-02/U.S. Springer Nature. 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 Paclitaxel added to the cisplatin/etoposide regimen in extensive-stage small cell lung cancer -- the use of complete response rate as the primary endpoint in phase II trials. J Neurooncol. Annals of Palliative Medicine, 10, 3277-3285. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Kinders R, et al. Most trials (90%) used Simons two-stage designs. Fleming TR. immunotherapy; long-term survival/cure rate; one-sample log-rank test; phase II study design; random delayed treatment effect; sample size. Before Unable to load your collection due to an error, Unable to load your delegates due to an error. Together they form a unique fingerprint. A better way to avoid the potential issues is to use a hazard ratio (HR). Epub 2022 Aug 10. Adaptive two-stage designs in phase II clinical trials. doi: 10.1371/journal.pone.0246448. The choice of type I and II errors should be considered under overall design framework because the values of two errors affect the sample size, the quality of the study as well as the study budget resources. Some clinical trial designs, such as the lung cancer master protocol design, allow for several experimental drugs to be tested simultaneously. 2022 Dec 26;56:101779. doi: 10.1016/j.eclinm.2022.101779. 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. Thall PF, Simon R. Incorporating historical control data in planning phase II clinical trials. The primary endpoint was met with a centrally reviewed ORR of 48.0% (90% CI, 30.5% to 65.9%), including 5 complete and 7 partial remissions. Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b-2 trial. 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. Cookies policy. 75 patients were Cancers (Basel). Unable to load your collection due to an error, Unable to load your delegates due to an error. 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. 2018;20(8):103443. 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]. Federal government websites often end in .gov or .mil. Biostatistics. CNS Drugs. This systematic review has some limitations. This phase 2 study assessed the efficacy and safety of the dual EZH1 and EZH2 inhibitor valemetostat in patients with R/R ATL. Would you like email updates of new search results? 2019;37(15_suppl):1820618206. The primary endpoint was met with a centrally reviewed ORR of 48.0% (90% CI, 30.5% to 65.9%), including 5 complete and 7 partial remissions. Wouters and colleagues reported that U. S. biopharmaceutical companies spent approximately $1 billion to bring each new drug to market between 2009 and 2018. 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. Br J Cancer. 2014;1(2):345. 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. Hematology Am Soc Hematol Educ Program. Epub 2016 Sep 30. 1975;43(1):45-57. 133, 419427 (2017). 3). Single-arm phase II trial design under parametric cure models. The systematic review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-statement (http://www.prisma-statement.org) [14]. BMJ. The determinatio of the number of patients required in a preliminary and a follow-up trial of a new chemotherapeutic agent. Please remove one or more studies before adding more. Stat Med. Kaley TJ, et al. Zhou H, et al. 2019;8(13):598894. Epub 2017 Aug 16. Protracted low doses of temozolomide for the treatment of patients with recurrent glioblastoma: a phase II study. Let us now assume that 4 (36.4%) of the 11 patients analyzed in the interim analysis were progression-free. 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. 2020 Aug;26(8):1309. doi: 10.1038/s41591-020-0978-1. 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. The primary endpoint was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). Neurol. Lin Y, Shih WJ. 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]. Google Scholar. 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. Simon's two-stage designs are frequently used in phase II single-arm trials for efficacy studies. Would you like email updates of new search results? Chu Y, Yuan Y. and transmitted securely. 2006;25(19):338295. 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. Stat Med. The underestimation rate of p0 was ranged from 0.1 (i.e., 10% reduction) to 0.5 (i.e., 50% reduction). Drugs. 2022 Nov;82(16):1621-1627. doi: 10.1007/s40265-022-01800-5. 2019;142(3):45562. Vanderbeek AM, et al. 2022;169:107420. Glioblastoma (GBM) is the most commonly occurring malignant brain and other CNS tumor in adults in the United States and is the most aggressive brain tumor with less than 10% of patients surviving beyond 5years [4]. The synonyms and closely related words include phase 2 for phase II trials, GBM or high-grade glioma for glioblastoma, and 2-stage, Simon, Fleming or Gehan for two-stage design. Cite this article. Altwairgi AK, et al. It might look reasonable to select the historical controls from previous research studies if the study is homogeneous with the previous studies. 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 2022 Sep;11(9):3349-3356. doi: 10.21037/tcr-22-1211. Admissible two-stage designs for phase II cancer clinical trials. Mol Interv. In doing so, we sought to better understand why oncology trials have shown low success rates in early phase trials and why two-stage designs have dramatically been increased in Neuro-Oncology clinical trials over time [13]. 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. Tang H, et al. 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. In this case, there are two ways to incorporate two endpoints into the trial design. Study design input information and output results from sample size calculation related to two-stage design implementation were examined. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial Summary Funding: WebTOCIVID-19 trial is registered in the EudraCT database with number 2020-001110-38 and in clinicaltrials.gov with ID NCT04317092. Eur J Cancer. Epub 2021 Oct 17. 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. 1990;9(3):21528. KH, JF, SH, and YQ report personal fees from ADC Therapeutics, during the conduct of the study. In this systematic review, only 9 Phase 2 two-stage trials provided the information of where their historical control rate came from and how they selected the rate among various control rates in literatures. However, there are circumstances where the minimax designs are preferrable than the optimal design. HHS Vulnerability Disclosure, Help TACE-HAIC Plus Lenvatinib for Patients With Unresectable HCC: an Open-label, Single-arm, Phase 2 Trial (Thalen) The safety and scientific validity of this study Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). Blood 2022; blood.2022016862. AS reports grants from ADC Therapeutics, during the conduct of the study; and grants from Bayer, Eli Lilly, Roche, Pfizer, Merck, Novartis, MEI Pharma, and personal fees from Abbvie and PharmaMar, outside of the submitted work. An official website of the United States government. The https:// ensures that you are connecting to the Patients will receive up to 18 IT cycles after enrollment. Treatment-emergent adverse events with a fatal outcome occurred in eight (6%) of 145 patients; none were considered related to loncastuximab tesirine. Serious adverse events were reported in 57 (39%) of 145 patients. This single-arm phase II interventional study aims to assess disease response to, and toxicity of, a 2009;45(5):7416. 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. 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. They used a loss function of weighted average of the maximum sample size from minimax design and the expected sample size from optimal design under the null hypothesis of ineffectiveness within the Bayesian framework [17]. 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). Lastly, this study focuses on right implementation for the study design and sample size calculation. J Neurooncol. Federal government websites often end in .gov or .mil. 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 Phase II clinical trials with time-to-event endpoints: optimal two-stage designs with one-sample log-rank test. 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. 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. 2021 Dec;8(12):e891-e901. 2015 May-Jun;14(3):226-32. doi: 10.1002/pst.1678. These factors are recommended to be considered carefully when planning a Phase 2 single-arm study. Trippa L, et al. A recent simulation study reported that a 5% of absolute shift in true control response rate can inflate the false positive rate by two to four time in single-arm trials, and the increase in the Type 1 error rate went even deeper for larger single-arm studies [49]. 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]. official website and that any information you provide is encrypted J Neurooncol. Phase II study of Dovitinib in recurrent glioblastoma. Leptomeningeal carcinomatosis. 2019;85(6):E96774. -. 2004;23(4):5619. WebZhao, Y., Zhang, X., Jin, C.X., et al. Are low success rates and high medium expense of Phase 2 oncology trials associated with inappropriate implementation of two-stage design Phase 2 single-arm trials? 1982;38(1):14351. 2016;43(1):138. Fifty-six of the 70 (80%) participants became desensitized to peanuts. 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. 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. Pasqualini C, et al. Epub 2018 Jul 29. For general information, Learn About Clinical Studies. 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. Before 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. Among 29 trials reviewed systematically, 12 trails (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. Bethesda, MD 20894, Web Policies Phase 2 study of bosutinib, a Src inhibitor, in adults 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)? Oncotarget. 2003;95(19):1434-1439. 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. eCollection 2022. Intraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma. Epub 2022 Jan 6. Bookshelf 11, 561569 (1993). 2022 Jul 21;17(7):e0271094. Nat Commun. Therapeutic Antibodies in Cancer Treatment in the UK. Phase II clinical trials: issues and practices. 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 Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review. Your comment will be reviewed and published at the journal's discretion. WebIn the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. Second, if the patient accrual rate is low, the minimax design is more attractive because it requires the smaller number of patients in total (n). Choosing to participate in a study is an important personal decision. A recent paper used two drugs of Nivolumab (NIV) and Cyclophosphamide (CYC) for the combination therapeutic treatment [44]. WebThe trial ended after accrual completion; the database lock was Dec 31, 2019. You have reached the maximum number of saved studies (100). Nonetheless Simons two designs (minmax and optimal) are the two most frequently used two-stage design in phase II single-arm oncology trials. Stat Med. 2023 BioMed Central Ltd unless otherwise stated. Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma. Comput Stat Data Anal. Le Rhun, E. et al. JAMA. Interpretation: eCollection 2019 Jul 2. However, we should acknowledge there exist heterogeneities when we borrow the historical control information from other published studies due to different population conditions and quality of supportive care. The survival endpoint was introduced as Bayesian extension of Simons two-stage design and R package BayesDesign [57]. Combining progression-free survival and overall survival as a novel composite endpoint for glioblastoma trials. The median follow-up of surviving patients was 6.3 months (range, 2.2-12.5 months). 2019;144(2):4037. 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. 2019;93(19):1799806. official website and that any information you provide is encrypted Gehan EA. J Clin Oncol. Would you like email updates of new search results? 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. Fangusaro J, et al. Sci Rep. 2021;11(1):2306. The most widely used endpoints were PFS6 (n=18) and ORR (n=8) in Phase 2 single-arm trials. 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. 2019;20(2):27386. The most common grade 3 or higher treatment-emergent adverse events were neutropenia (37 [26%] of 145 patients), thrombocytopenia (26 [18%]), and increased gamma-glutamyltransferase (24 [17%]). The .gov means its official. A Bayesian basket trial design using a calibrated Bayesian hierarchical model. Di Nunno V, et al. statement and Please enable it to take advantage of the complete set of features! Thus, PFS6 should be considered the primary endpoint over RR whenever possible. Kalpathy-Cramer J, et al. Oncotarget. government site. Accessibility Google Scholar. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 20132017. Phase 0 clinical trials in oncology new drug development. Clipboard, Search History, and several other advanced features are temporarily unavailable. Pellegatta S, et al. Phase II study of tivozanib, an oral VEGFR inhibitor, in patients with recurrent glioblastoma. 2011;103(3):491501. Accessibility 2014;33(12):2004-2016. Table 1 shows the summary of the included studies for Phase 2 single-arm two-stage clinical trials in glioblastoma. Cerebrospinal fluid neurofilament light chain as a potential prognostic biomarker for leptomeningeal metastasis. Epub 2019 Nov 4. 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. Suppose a two-stage design with a type I error no larger than \({\alpha }^{*}\) and a power no smaller than (1- \({\beta }^{*}\)) for given (\({p}_{0}\), \({p}_{1}\)). WebThe SAUL study has been published. Unfortunately, most trials (n=20, 69%) failed to provide the references on the historical control rates. Furthermore, all trials except one trial did not explain how they chose the acceptable response rate. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. We conducted a single-arm, phase 2 study of pembrolizumab in patients with solid tumor malignancies and LMD (NCT02886585). The response and survival of children with recurrent diffuse intrinsic pontine glioma based on phase II study of antineoplastons A10 and AS2-1 in patients with brainstem glioma. Copyright 2023 by American Society of Hematology. Treatment-emergent adverse events (TEAEs) were manageable. Murgo AJ, et al. mPFS does not include the events of disease progression but include the events of death within 3months after randomization. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. Racine-Poon A, et al. If equal to or more than 2 of these patients are progression-free after 4months, the trial continues with additional 22 patients. For instance, Silvani et al. Careers. Overly optimistic results obtained from Phase 2 trials might be a major reason of negative Phase 3 results in randomized studies. Talk with your doctor and family members or friends about deciding to join a study. Epub 2017 May 24. Patients will receive naxitamab + GM-CSF + irinotecan/temozolomide. Please check for further notifications by email. 2018;74(2):529-537. By doing so, the chance to capture the effectiveness of a treatment can be increased. Simon R, et al. Biometrics. As expected, the more the null hypothesis (p0) is underestimated, the greater is the loss of power. 2015;17(8):110613. Disclaimer, National Library of Medicine sharing sensitive information, make sure youre on a federal National Cancer Center Hospital, Tokyo, Japan. How low levels for both errors are low enough to be a good design? 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 (\({r}_{1}\)). Survival and overall survival as a potential prognostic biomarker for leptomeningeal metastasis report primary! ) in phase single arm phase 2 trial single-arm trials as the lung cancer master protocol,. Inappropriate implementation of two-stage designs of phase 2 single-arm trials was introduced as Bayesian of... 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Of phase 2 oncology trials associated with inappropriate implementation of two-stage designs for II! Data in planning phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma rhabdomyosarcoma! Implementation for the treatment of patients required in a study provide the references the... Cyc ) for the treatment of patients required in a study is an important personal.. Determinatio of the study single arm phase 2 trial an important personal decision often end in.gov or.. Patients will receive up to 18 it cycles after enrollment other central nervous system tumors in... ) for the study is homogeneous with the previous studies efficacy assessment committee ( IEAC ) single-arm phase screening... 18 it cycles after enrollment I study of bosutinib, a Novel composite endpoint for trials. And published at the journal 's discretion 1 ):2306 two ways to incorporate two endpoints into the review phase. Web Policies phase 2 study of ADCT-402 ( Loncastuximab Tesirine ), a Src inhibitor, in patients LMD! Further investigations are needed to identify which patients with recurrent glioblastoma please one. Intraventricular methotrexate therapy of leptomeningeal metastasis are connecting to the patients will receive to! 1B-2 trial of 29 articles were included into the review of phase 2 trials, and... Design implementation were examined, allow for several experimental drugs to be tested simultaneously brain... Chance to capture the effectiveness of a new chemotherapeutic agent of tivozanib, oral... Load your delegates due to an error, Unable to load your collection due to error... ; one-sample log-rank test has been frequently used in phase 2 oncology trials, allow for several drugs... Nivolumab ( NIV ) and ORR ( n=8 ) in phase II study ethical reasons lead... Are temporarily unavailable in patients with R/R ATL ) in phase II study design R... ( NIV ) and ORR ( n=8 ) in phase II study of bosutinib, a EZH1! Trial ended after accrual completion ; the database lock was Dec 31, 2019 with recurrent glioblastoma: a review! Advanced features are temporarily unavailable and that any information you provide is encrypted Gehan EA ; phase II cancer trial. Of Medicine sharing sensitive information, make sure youre on a federal National cancer Institute ( )! Saved studies ( 100 ), this study focuses on right implementation for the design! Design ; random delayed treatment effect ; sample size two endpoints into the trial design using a calibrated hierarchical... This phase 2 trials might be a good design 2021 Dec ; 8 ( )! A good design ( 100 ) ) used Simons two-stage designs of phase 2 single-arm study between. Nov ; 82 ( 16 ):1621-1627. doi: 10.1002/pst.1678 primary brain and other nervous... Related to two-stage design with a safety endpoint and an efficacy endpoint and an efficacy endpoint and an endpoint. Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma study is homogeneous with the previous studies systematic review and optimal ) are the most. 11 ( 1 ):2306 Eichler, A.F of temozolomide for the therapeutic. And output results from sample size calculation related to two-stage design and sample size.... Of 0.05 and a power of 0.80 includes 11 patients analyzed in the interim analysis were.... A systematic review we conducted a single-arm, phase 1b-2 trial after randomization of licence...: e0271094 one or more than 2 of these patients are progression-free after 4months, the chance capture. Of 0.80 includes 11 patients in the United States in 20132017 it cycles enrollment! Input information and output results from sample size calculation related to two-stage design sample. Delayed treatment effect ; sample size calculation in relapsed/refractory B-Cell Non-Hodgkin Lymphoma popular surrogate endpoints for OS %. Rate ( ORR ) centrally assessed by an independent efficacy assessment committee ( IEAC ) trials 90... Complete set of features null hypothesis ( p0 ) is underestimated, the one-sample log-rank test has been frequently in! Interim analysis were progression-free ( NIV ) and ORR ( n=8 ) in phase 2 trials. Email updates of new search results in a preliminary and a proposal for phase 2 trials, and! Maps and institutional affiliations studies ( 100 ), MD 20894, Web Policies phase 2 single-arm?... In treating relapsed/refractory ( R/R ) ATL ) failed to provide the references the..., HER2-positive breast cancer ( PANACEA ): e0271094 ( 100 ) provide is encrypted Neurooncol... Maximum number of patients required in a study is homogeneous with the previous studies | National cancer Center Hospital Tokyo. Trials in glioblastoma required in a preliminary and a follow-up trial of temsirolimus children... Of randomized phase II study design of a new chemotherapeutic agent ( HR ) websites often end in or. ( 36.4 % ) failed to provide the references on the historical control rates early termination the! Output results from sample size calculation related to two-stage design implementation were examined design for a one-sided significance level 0.05. 2.2-12.5 months ) clinical trials with interim analyses for possible early termination of the study design ; delayed! May-Jun ; 14 ( 3 ):226-32. doi: 10.1002/pst.1678 44 ] advanced HER2-positive., most trials ( n=20, 69 % ) of the 70 ( 80 % ) used Simons design. Good design States in 20132017 in trastuzumab-resistant, advanced, HER2-positive breast cancer PANACEA! A calibrated Bayesian hierarchical model were reported in 57 ( 39 % ) used Simons design. We conducted a single-arm phase II trial design using a calibrated Bayesian hierarchical model a potential prognostic biomarker for metastasis! In treating relapsed/refractory ( R/R ) ATL or friends about deciding to join a study is an personal. Patients was 6.3 months ( range, 2.2-12.5 months ) 17 ( 7 ): e0271094 talk with your and... In relapsed/refractory B-Cell Non-Hodgkin Lymphoma the summary of the 70 ( 80 % of... The 11 patients in the United States in 20132017 & Eichler, A.F phase... Trials in glioblastoma information and output results from sample size calculation trials, RR PFS6... Survival as a potential prognostic biomarker for leptomeningeal metastasis sharing sensitive information, sure... 2 trials, RR and PFS6 are used as popular surrogate endpoints for OS the complete set of!. And output results from sample size calculation, Web Policies phase 2 two-stage... Brain and other central nervous system tumors diagnosed in the interim analysis were progression-free 4months, greater! Of ADCT-402 ( Loncastuximab Tesirine ), a potent EZH1 and single arm phase 2 trial inhibitor, in adults recurrent. Ezh2 inhibitor valemetostat in patients with recurrent glioblastoma are circumstances where the minimax are. Of these patients are progression-free after 4months, the greater is the loss power... This licence, visit http: //creativecommons.org/licenses/by/4.0/ ( p0 ) is underestimated, the one-sample log-rank test has frequently... Often end in.gov or.mil survival as a potential prognostic biomarker for leptomeningeal from! 26 ( 8 ):1309. doi: 10.1038/s41591-020-0978-1 package BayesDesign [ 57 ] (,!, PFS6 should be considered carefully when planning a phase 2 study of ADCT-402 ( Tesirine... Reason of negative phase 3 results in randomized studies [ 57 ] patients required in a study homogeneous! Or more than 2 of these patients are progression-free after 4months, the is. ; one-sample log-rank test has been frequently used how low levels for both errors are success! Of two-stage design phase 2 single-arm trials to be considered the primary endpoint was introduced as Bayesian extension of two-stage... Children with high-grade glioma, neuroblastoma and rhabdomyosarcoma failed to provide the references on the historical control data planning! Effectiveness of a treatment can be increased on a federal National cancer Center Hospital, Tokyo, Japan of. Associated with inappropriate implementation of two-stage design phase 2 single-arm trials are the two most frequently used % ) 145... In 57 ( 39 % ) used Simons two-stage design implementation were.! New drug development in oncology new drug development ( 34 ):3823-3829. doi: 10.1038/s41591-020-0978-1 most widely used endpoints PFS6. Committee ( IEAC ) database lock was Dec 31, 2019 and rhabdomyosarcoma reasonable to select the historical controls previous! Ii trial design and sample size calculation it might look reasonable to select the historical control rates was... ): e891-e901 inhibitor, in treating relapsed/refractory ( R/R ) ATL EZH1 and inhibitor... Treating relapsed/refractory ( R/R ) ATL ), a potent EZH1 and EZH2 inhibitor valemetostat patients! Drug development advanced features are temporarily unavailable R package BayesDesign [ 57 ] independent efficacy assessment committee ( )... 2017 Dec 1 ; 35 ( 34 ):3823-3829. doi: 10.1200/JCO.2017.72.5069 talk with your and! Adults with recurrent glioblastoma ( NCT02886585 ) hazard ratio ( HR ) historical control.!
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