single arm phase 2 trial

Eur J Cancer. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. 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. For the trial, 70 children aged 618 years old with peanut allergies received 12-hour boiled peanuts for 12 weeks, 2-hour boiled peanuts for 20 weeks, and roasted peanuts for 20 weeks, to a target maintenance dose of 12 roasted peanuts daily. 2011;2(1):1322. J Neurooncol. The sample size calculation for the two-stage designs is determined based on the historical control rate and difference between the two rates (\({p}_{0}, {p}_{1}\)). Cancer 124, 2135 (2018). Cancer immunotherapy trial design with long-term survivors. Simons two-stage designs include optimal and minimax design [6], while other two-stage designs include Fleming, Gehan, admissible two-stage design [15,16,17]. Oncotarget. 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. 2003;95(19):1434-1439. 2017;36(21):330214. 2013;24(4):11129. 2019;142(3):45562. WebPhase II Two-Stage Single-Arm Clinical Trials for Testing Toxicity Levels Simon's two-stage designs are frequently used in phase II single-arm trials for efficacy studies. This work was supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute. 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. 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. Epub 2021 May 11. Compressing drug development timelines in oncology using phase 0 trials. A total of four scenarios were examined according to null (p0) and alternative (p1) response rates such as Case 1: p0=0.1 and p1=0.3, Case 2: p0=0.3 and p1=0.5, Case 3: p0=0.5 and p1=0.7, and Case 4: p0=0.7 and p1=0.9. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. This site needs JavaScript to work properly. Nat Rev Cancer. J Clin Oncol. The purpose of this study is to evaluate the efficacy and safety in patients with FGFR2-Rearranged unresectable or metastatic intrahepatic cholangiocarcinoma who failed prior therapy Arms and Interventions Arm: Experimental Drug ICP-192 Outcome Measures Simon R, et al. Unable to load your collection due to an error, Unable to load your delegates due to an error. Epub 2019 Nov 26. The early phase of trials might encounter a considerable amount of uncertainty when planning a trial. 2001 May;32(2):155-62. doi: 10.1016/s0169-5002(00)00220-8. Dowlati A, Crosby L, Remick SC, Makkar V, Levitan N. Lung Cancer. FOIA Furthermore, a couple of trials did not provide explanation and description about the results of sample size calculation (no shown here). In this case, there are two ways to incorporate two endpoints into the trial design. An official website of the United States government. Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b-2 trial. 2015;17(8):110613. J Neurooncol. Epub 2022 Apr 1. and transmitted securely. Glioblastoma: emerging treatments and novel trial designs. Tawbi HA, et al. Optimal, minimax and admissible two-stage design for phase II oncology clinical trials. 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 J. Clin. Bethesda, MD 20894, Web Policies 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. 2014;30(12):205161. Therapeutic Antibodies in Cancer Treatment in the UK. For good study design with phase II trials, investigators should maintain low level of type I and II errors. Phase II study of Dovitinib in recurrent glioblastoma. Keywords: Wang Z-X, et al. 2020 Nov 28;20:100678. doi: 10.1016/j.conctc.2020.100678. 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. Eastern Cooperative Oncology Group. Among 23 Simons two-stage designs, 12 trials used Simons optimal designs, 4 trials used Simons minimax designs, and 7 trials just mentions Simons two-stage designs without specific design types of the two, Optimal and Minimax. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. A total of 29 articles were included into the review of Phase 2 two-stage trials in glioblastoma. Thank you for submitting a comment on this article. 8600 Rockville Pike The proportion of patients obtaining a centrally assessed complete response (CR) or partial response (PR) according to the International Neuroblastoma Response Criteria (INRC), The proportion of patients obtaining a centrally assessed CR or PR according to the INRC, The time from first centrally assessed overall response (OR) (CR or PR according to the INRC) to PD or death, the proportion of patients obtaining a centrally assessed CR according to the INRC, the time from initiation of IMP treatment until death or start of new anti-cancer treatment (prohibited as per protocol), the time from enrollment until progressive disease or death, whichever comes first, The proportion of patients alive and with no PD, Drug: Naxitamab and GM-CSF in combination with irinotecan and temozolomide. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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. Accessibility FOIA We also sought to understand how these two-stage trials have been implemented, and discussion of potential design issues which we hope will be helpful for investigators work with Phase 2 clinical trials in rare and high-risk cancer studies including Neuro-Oncology. Muhic A, et al. The .gov means its official. Lassman AB, et al. eCollection 2019 Jul 2. Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. 2007;7(6):32534. Most frequently used population was adult patients with recurrent glioblastoma. Clipboard, Search History, and several other advanced features are temporarily unavailable. Rubinstein LV, et al. WebIn the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next? 2021 May 6;134(11):1299-1309. doi: 10.1097/CM9.0000000000001463. Semin Oncol. Contemp Clin Trials. The https:// ensures that you are connecting to the HHS Vulnerability Disclosure, Help J Neurooncol. In this phase 2 study, we demonstrated that treatment with single-agent PD-1 inhibitor was safe and associated with a 3-month OS of 60% in a heavily pre-treated 2022 Dec 7;14(24):6026. doi: 10.3390/cancers14246026. Silvani A, et al. 2022 Dec 26;56:101779. doi: 10.1016/j.eclinm.2022.101779. Phase II study of tivozanib, an oral VEGFR inhibitor, in patients with recurrent glioblastoma. Transparency comes from providing information on historical control rates borrowed from the literature as well as expected response rates from the experimental agent. 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. 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. 1961;13:34653. Example of Adaptive Design to handle the uncertainty for Phase 2 two-stage design. We restricted the phase II clinical trials in glioblastoma to those published in 2011 or later. Disclaimer, National Library of Medicine We conducted a single-arm, phase 2 study of pembrolizumab in patients with solid tumor malignancies and LMD (NCT02886585). 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 2017;131(3):60310. Patients were required to have ECOG PS2 and disease progression during or following 13 prior treatments. Glioblastoma clinical trials: current landscape and opportunities for improvement. An increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal1-3. The author(s) read and approved the final manuscript. Bethesda, MD 20894, Web Policies 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. 2006;25(19):338295. Epub 2017 Aug 16. Design issues of randomized phase II trials and a proposal for phase II screening trials. 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. Only three trials (11%) provided key input parameters, appropriately reported output results from sample size calculation of two-stage designs, and finally provided the reference and explanation of historical control rates. 2021;39(1):22631. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). The discrete conditional error based adaptive design method requires to recalculate the probability of rejection region using the results from the first stage. Estimation of clinical trial success rates and related parameters. Please enable it to take advantage of the complete set of features! 1996 Oct;74(8):1317-20. doi: 10.1038/bjc.1996.537. Trippa and colleges [55] introduced a novel composite endpoint model by combining PFS6 and OS for glioblastoma trials. The era of CD19-directed therapy in diffuse large B-cell lymphoma. Admissible two-stage designs for phase II cancer clinical trials. Careers. The clinical trials landscape for glioblastoma: is it adequate to develop new treatments? Secondary objectives included toxicity, response rate and time to intracranial or extracranial disease progression. J Clin Oncol. Epub 2020 Sep 1. The determinatio of the number of patients required in a preliminary and a follow-up trial of a new chemotherapeutic agent. As expected, the more the null hypothesis (p0) is underestimated, the greater is the loss of power. HHS Vulnerability Disclosure, Help A comprehensive study on identification of good surrogate endpoints for overall survival and determination of robust historical control rates will be performed to generate a recommended guideline for clinical researchers. 2022 Feb 20;41(4):786-797. doi: 10.1002/sim.9258. Taylor JW, et al. Stat Med. Part of Analysis of survival data under the proportional hazards model. The outcomes of simulation are depicted in Fig. 1989;10(1):110. 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]. 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. Int Stat Rev/Revue Int de Stat. 2022 May;169:107420. doi: 10.1016/j.csda.2021.107420. Publisher Correction: Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. We enrolled patients aged 18 years with HER2-positive breast cancer and newly An armof a clinical trial is a group of patients receiving a specific treatment (or no treatment). 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. 2021;11:660892. 2012;4(4):799801. Intrathecal administration of trastuzumab for the treatment of meningeal carcinomatosis in HER2-positive metastatic breast cancer: a systematic review and pooled analysis. Kalpathy-Cramer J, et al. and transmitted securely. 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. 2022 Jul 21;17(7):e0271094. Epub 2019 Nov 4. Copyright 2023 by American Society of Hematology. Cancers (Basel). Due to economical and ethical reasons, the two-stage designs have been widely used for Phase 2 single-arm trials in oncology because the designs allow us to stop the trial early if the proposed treatment is likely to be ineffective. 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. Wonsuk Yoo. Treatment-emergent adverse events (TEAEs) were manageable. 2004;23(4):5619. Biometrics. 2018;7(4):e1412901. sharing sensitive information, make sure youre on a federal -. Clipboard, Search History, and several other advanced features are temporarily unavailable.
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