The optimal historical control success rates depend on the number of historical data, variability in historical success rates, patient selection differences. Weighted log-rank test for time-to-event data in immunotherapy trials with random delayed treatment effect and cure rate. But interestingly almost 60% of studies (17/29, 59%) failed to provide at least one key output results of sample size calculation such as the number of samples of first stage and both stages (\({n}_{1}, n\)) and the treatment rejection numbers of the first stage and both stages (\({r}_{1}, r\)). This site needs JavaScript to work properly. One-sample multiple testing procedure for phase II clinical trials. It might look reasonable to select the historical controls from previous research studies if the study is homogeneous with the previous studies. 2017;131(3):60310. Would you like email updates of new search results? To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Exploration of modified progression-free survival as a novel surrogate endpoint for overall survival in immuno-oncology trials. 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 2013 May;139(1):13-22. doi: 10.1007/s10549-013-2525-y. J Cancer. 2010;28(11):193641. Talk with your doctor and family members or friends about deciding to join a study. 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. eCollection 2021. Experimental arms, which receive an experimental drug, are compared with control arms, which can receive an active comparator (another therapy used to treat the same condition as the experimental therapy), a placebo comparator (an inactive therapy), a sham comparator (an inactive therapy made to look identical to the active therapy), or no intervention. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. PLoS One. In the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. 2022 Feb 20;41(4):786-797. doi: 10.1002/sim.9258. The .gov means its official. Nat Commun. Wouters OJ, McKee M, Luyten J. Analysis of survival data under the proportional hazards model. [37] used Simons two-stage optimal design to evaluate the target PFS6 of 35% against the null PFS6 of 20% to achieve 90% power at a 1-sided 10% level, resulting in the required sample size of 58 patients. Biometrics. 2018;20(8):103443. BMC Med Res Methodol 22, 327 (2022). Copyright 2021 Elsevier Ltd. All rights reserved. 2021;13(3):28694. Keywords: HHS Vulnerability Disclosure, Help 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]. The median follow-up of surviving patients was 6.3 months (range, 2.2-12.5 months). Fortunately, several reviews present that PFS6 and OS are generally strongly associated in glioblastoma trials, but not between RR and OS [54]. Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. Most studies (n=27, 93%) provided the number of patients in stage 1 and both stages, so many trials (n=17) failed to report one or more from both response numbers of stage 1 and both stages which are key information to determine the study continuation toward the second stage (\({r}_{1}\)) at the end of first stage and hypothesis testing of efficacy (\(r\)) at the end of second stage. 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. We enrolled patients aged 18 years with HER2-positive breast cancer and newly Naxitamab and GM-CSF will be given for at least 8 cycles. Polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed or refractory follicular lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study. Tang H, et al. Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase II multicenter clinical trial. 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. 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. Wu X, Wu C, Liu F, Zhou H, Chen C. A generalized framework of optimal two-stage designs for exploratory basket trials. Some clinical trial designs, such as the lung cancer master protocol design, allow for several experimental drugs to be tested simultaneously. Biometrics. Sort by Weight Alphabetically Medicine and Dentistry Patient Recent research reported that the success rate in proceeding from Phase 2 to Phase 3 was the lowest among all three rates of Phase 1 to 2, Phase 2 to 3, and Phase 3 to approval (e.g., 29.7%, 20.3%, and 35.5% for oncology and 35.2%, 27.4%, 59% for overall) [2]. 2022 Dec 6;15:1481-1501. doi: 10.2147/OTT.S326632. 2015;17(8):110613. Privacy 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]. Most trials (90%) used Simons two-stage designs. 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. 1975;43(1):45-57. 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. Cancer 124, 2135 (2018). Copyright 2023 by American Society of Hematology. Treatment-emergent adverse events (TEAEs) were manageable. Listing a study does not mean it has been evaluated by the U.S. Federal Government. 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. And 7 trials were used with (1) 5% and 20% (2) 10% and 10% as their type 1 and 2 errors respectively. doi: https://doi.org/10.1182/blood.2022016862. mPFS does not include the events of disease progression but include the events of death within 3months after randomization. This site needs JavaScript to work properly. 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). 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 2020 Sep 1. 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. Eur J Cancer. Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. GBM: glioblastoma, PFS6: progression-free survival at 6months, Key info: key input parameters for two-stage design, Right SS: did two-stage sample size calculation be appropriately implanted? J Neurooncol. All authors reviewed the manuscript. The primary endpoint was rate of overall survival at 3 months (OS3). The x-axis is underestimation rate of a null hypothesis and y-axis is loss of power from the power of 80%. J Neurooncol. 2022 Nov;82(16):1621-1627. doi: 10.1007/s40265-022-01800-5. Epub 2022 Jan 6. 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. Ostrom QT, et al. sharing sensitive information, make sure youre on a federal J Neurooncol. Bayesian single-arm phase II trial designs with time-to-event endpoints. Multistage designs for phase II clinical trials: statistical issues in cancer research. 2021 Jun;22(6):741-742. doi: 10.1016/S1470-2045(21)00191-1. Copyright 2020 Friends of Cancer Research. Google Scholar. Among appropriately implemented 12 trials, discouragingly only 3 trials (10%) explained the reference information of historical control rates. We conducted a single-arm, 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. Ann Oncol. 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. 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. Bayesian hierarchical modeling of patient subpopulations: efficient designs of Phase II oncology clinical trials. 8600 Rockville Pike Overly optimistic results obtained from Phase 2 trials might be a major reason of negative Phase 3 results in randomized studies. (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)? Epub 2020 Jun 5. doi: 10.1016/S2352-3026(22)00072-2. 2012;48(2):25362. 2016;43(1):138. 2019 Mar;20(3):371-382. doi: 10.1016/S1470-2045(18)30812-X. (Yes, No), (8) all four output results of sample size appropriately reported? 1982;38(1):14351. official website and that any information you provide is encrypted WebRandomized and Single-Arm Trials An arm of a clinical trial is a group of patients receiving a specific treatment (or no treatment). Pembrolizumab is safe and feasible and displays promising activity in patients with LMD. Bethesda, MD 20894, Web Policies A systematic review of surrogate endpoints (SEPs) for overall survival (OS) in metastatic colorectal cancer mCRC. All rights reserved. Together they form a unique fingerprint. Pharm Stat. Phase II open-label study of nintedanib in patients with recurrent glioblastoma multiforme. 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. 2019;8(13):598894. CAS 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]. and transmitted securely. FOIA Funding: Epub 2016 Sep 30. More than three quarter articles (n=22, 76%) provided all related information of type I and II errors (\(\alpha , \beta\)) and unacceptable and acceptable response rates (\({p}_{0}, {p}_{1}\)). Federal government websites often end in .gov or .mil. Drugs. Neurosurg. Cerebrospinal fluid neurofilament light chain as a potential prognostic biomarker for leptomeningeal metastasis. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. 2021;372:n160. 2018;7(4):e1412901. Kaley TJ, et al. Pharm Stat. J Clin Oncol. We provide a real-life application and a free R package gen2stage to facilitate direct use of such two-stage designs in a safety study. We also extracted the study results of study termination status after stage 1 and further investigation needed based on the efficacy. In addition, the several trials provided wrong results from sample size calculation even if they reported all related key information for two-stage design implementation (not shown in table). 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. 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. Springer Nature. This multicenter phase 2 trial (NCT04102150; https://clinicaltrials.gov/ct2/show/NCT04102150; DS3201-A-J201) enrolled patients with R/R aggressive ATL (acute, lymphoma, unfavorable chronic type). Among appropriately implemented 12 trials, discouragingly only 3 trials (10%) explained the reference information of historical control rates. Oncoimmunol. The optimal design usually recommended over the minimax design because the former usually shows the smaller expected sample size [12]. Epub 2019 Feb 11. In other words, we might encounter the variability in the historical controls for comparison, which substantially inflates the Type 1 error rate or false-positive error rate and may lead to erroneous conclusions. J Neurooncol. 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. 2014;1(2):345. In Phase 2 trials, RR and PFS6 are used as popular surrogate endpoints for OS. Zagouri F, Sergentanis TN, Bartsch R, Berghoff AS, Chrysikos D, de Azambuja E, Dimopoulos MA, Preusser M. Breast Cancer Res Treat. J Neurooncol. Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis. 2019;10(14):321423. 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. Br J Cancer. Federal government websites often end in .gov or .mil. Pembrolizumab in Patients With Extensive-Stage Small-Cell Lung Cancer: Results From the Phase Ib KEYNOTE-028 Study. Chu Y, Yuan Y. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International. Hematology Am Soc Hematol Educ Program. An armof a clinical trial is a group of patients receiving a specific treatment (or no treatment). Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme. Hu J, et al. 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. J Clin Oncol. J Neurooncol. official website and that any information you provide is encrypted Phase II trial of triple tyrosine kinase receptor inhibitor nintedanib in recurrent high-grade gliomas. J Clin Oncol. WebZhao, Y., Zhang, X., Jin, C.X., et al. 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. Lee EQ, et al. 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. In this manner, the two-stage designs allow stopping of a futile trial early. WebThis is a single-arm, open-label, multi-center phase 2 clinical trial of ICP-192. Estimation of clinical trial success rates and related parameters. Jung SH, et al. Cannistra SA. Wu J, Pan H, Hsu CW. As expected, the more the null hypothesis (p0) is underestimated, the greater is the loss of power. and transmitted securely. 1800 M Street NW, Suite 1050 South,Washington, DC 20036Phone: (202) 944-6700. An official website of the United States government. Brenner AJ, et al. Diagnosis and treatment patterns for patients with leptomeningeal metastasis from solid tumors across Europe. Please enable it to take advantage of the complete set of features! [56] proposed modified PFS (mPFS) for immune-oncology trials. Control Clin Trials. Du XJ, et al. PLoS One. 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)? Loncastuximab tesirine: an effective therapy for relapsed or refractory diffuse large B-cell lymphoma. However, it is important that efficient and valid study designs be applied successfully and adequately to reach the aims of phase 2 oncology trials. 2022 Dec 26;56:101779. doi: 10.1016/j.eclinm.2022.101779. Epub 2021 Oct 17. For general information, Learn About Clinical Studies. 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. 2013;10(5):72034. 2022 May;169:107420. doi: 10.1016/j.csda.2021.107420. 2017 Dec 1;35(34):3823-3829. doi: 10.1200/JCO.2017.72.5069. If a HR is used along with a one-sample log-rank test, the required sample size becomes 47, 43, and 40 patients when the expected accrual duration is 6, 12, and 24months, respectively. Epub 2015 Apr 1. 2012;4(4):799801. Sci Rep. 2021;11(1):2306. 1996 Oct;74(8):1317-20. doi: 10.1038/bjc.1996.537. A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma. Brastianos PK, Strickland MR, Lee EQ, Wang N, Cohen JV, Chukwueke U, Forst DA, Eichler A, Overmoyer B, Lin NU, Chen WY, Bardia A, Juric D, Dagogo-Jack I, White MD, Dietrich J, Nayyar N, Kim AE, Alvarez-Breckenridge C, Mahar M, Mora JL, Nahed BV, Jones PS, Shih HA, Gerstner ER, Giobbie-Hurder A, Carter SL, Oh K, Cahill DP, Sullivan RJ. 8600 Rockville Pike Hargrave D, et al. 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. 2019;144(2):35968. The .gov means its official. Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next? A phase II study of O6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brainstem gliomas: a Pediatric Brain Tumor Consortium study. Inclusion of non-inferiority analysis in superiority-based clinical trials with single-arm, two-stage Simon's design. Korean J Radiol. 2021 Jan;20(1):117-128. doi: 10.1002/pst.2060. Before All other rights reserved. 2022;169:107420. WebAn increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal 1-3. J Neurooncol. Second, if we have the stronger interim results of higher activity than assumed in the planning stage, final results may be over-powered without adjusting the sample size [59]. official website and that any information you provide is encrypted Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review. Pharm Stat. Clinical end points in recurrent glioblastoma: are antiangiogenic agents friend or foe? 2013;111(3):34753. 75 patients were A complete systematic review and discussions for overcoming design issues might be important to better understand why oncology trials have shown low success rates in early phase trials. Yoo, W., Kim, S., Garcia, M. et al. Thus, the key input parameters (\(\alpha , \beta , {p}_{0}, {p}_{1}\)) and output results (\({n}_{1}, n, {r}_{1}, r\)) were investigated to assess the appropriate usage and report of the two-stage phase 2 trials. The primary endpoint was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). Article 2021;150:5362. Systemic Therapy Approaches for Breast Cancer Brain and Leptomeningeal Metastases. 2020 Aug;26(8):1309. doi: 10.1038/s41591-020-0978-1. 2020 Jul;21(7):978-988. doi: 10.1016/S1470-2045(20)30225-4. 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. 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. There was no language restriction, but only complete papers published in peer-reviewed journals were considered. 2015;121(3):55763. Unable to load your collection due to an error, Unable to load your delegates due to an error. Lancet Oncol. The median PFS of 4.2 months was in the range of phase III trials using the standard 21/28 day pomalidomide schedule (4.04.6 months) [1, 2]. 2011;2(1):1322. 2018;15(2):14958. Google Scholar. For instance, Silvani et al. Treatment-emergent adverse events (TEAEs) were manageable. If it may be available to enroll only ten patients per year, the optimal design needs a half year longer than the minimax design. 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 Novak 2 , Erika Lerch 5 , Galle Rhyner Agocs 6 , Atorvastatin in combination with radiotherapy and temozolomide for glioblastoma: a prospective phase II study. In this systematic review, we have examined 29 studies from Phase 2 single-arm two-stage trials in glioblastoma to assess the appropriateness and transparency of the study design and sample size calculation of Phase 2 single-arm two-stage trials in glioblastoma. Wonsuk Yoo. End of study was approximately 8 1 weeks (57 7 days) after the first drug administration. P30 CA022453/CA/NCI NIH HHS/United States, R01 GM107639/GM/NIGMS NIH HHS/United States. J Nat Cancer Inst. -, Ongerboer de Visser, B. W. et al. Muhic A, et al. 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. Kinders R, et al. Phase II study of Dovitinib in recurrent glioblastoma. JAMA. Design issues of randomized phase II trials and a proposal for phase II screening trials. doi: 10.1016/S2352-3026(21)00311-2. J Clin Oncol. 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'. The underestimation rate of p0 was ranged from 0.1 (i.e., 10% reduction) to 0.5 (i.e., 50% reduction). Tawbi HA, et al. (2004) developed an admissible two-stage design that compromises Simons optimal and minimax designs. 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]. Stat Med. Fangusaro J, et al. Part of Please enable it to take advantage of the complete set of features! Epub 2022 Aug 10. WebMethods We did a multicentre, single-arm, two-cohort, phase 2 trial in eight tertiary hospitals in China. Its interesting to see that most trials without mentioning specific design types (like Simons optimal or minimax, Gehan, Fleming, or admissible designs) failed to provide one or more than one key information for the implementation results of two-stage design sample size calculation. WebIn the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. Nonetheless, none has examined the usage for published articles that had applied the two-stage designs in Phase 2 single-arm trials in brain tumor. official website and that any information you provide is encrypted There is no universal solution to handle the variability around historical control data since the selected design depends on judgements to the specific study circumstances. Please enable it to take advantage of the complete set of features! and transmitted securely. Most frequently used population was adult patients with recurrent glioblastoma. Before Altwairgi AK, 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%). Admissible two-stage designs for phase II cancer clinical trials. Eur J Cancer. Accessibility We identified a total of 81 articles based on online search using Two-stage Phase II trials in glioblastoma. The other three trials used two-stage designs like Inadmissible design, Fleming and Gehan designs. PMC Phase 2 study of Pomalidomide (CC-4047) monotherapy for children and young adults with recurrent or progressive primary brain tumors. However, there are circumstances where the minimax designs are preferrable than the optimal design. Valemetostat 200 mg orally once daily demonstrated promising efficacy and manageable toxicity in heavily pretreated patients. Please enable it to take advantage of the complete set of features! Brastianos, P.K., Brastianos, H. & Eichler, A.F. Copyright 2022 American Society of Hematology. Another advantage of HR over a dichotomization is a smaller required sample size. 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. 2007;7(2):1319. Friends of Cancer Research is a 501 (C)(3) non-profit organization.Our tax ID number is 52-1983273. Dhakal A, Van Swearingen AED, O'Regan R, Anders CK. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. Accessibility Detailed Description: This is an international, single-arm, multicenter phase 2 trial, in Bookshelf The https:// ensures that you are connecting to the Fleming TR. Le Rhun, E. et al. Phase II clinical trials: issues and practices. https://doi.org/10.1186/s12874-022-01810-7, DOI: https://doi.org/10.1186/s12874-022-01810-7. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial Summary Accessibility Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. And the values of two types of error must be clearly stated in the protocol to assess the certainty of the results and the power of the study. 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. Even though Simons two-stage designs have been popularly in oncology Phase 2 trials during last two decades, none, to our knowledge, has examined the usage for published articles that had applied the two-stage designs in Phase 2 single-arm trials in brain tumors. in Central Nervous System Metastasis, the Biological Basis and Clinical Consideraiton (ed. Epub 2017 Aug 16. Di Nunno V, et al. Naxitamab and Granulocyte-Macrophage Colony Stimulating Factor in Combination With Irinotecan and Temozolomide in Patients With High-Risk Neuroblastoma With Primary Refractory Disease or in First Relapse. Article 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. 2018;74(2):529-537. 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. 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. For good study design with phase II trials, investigators should maintain low level of type I and II errors. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. Among 29 trials reviewed systematically, 12 trails (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. Neuro Oncol. 133, 419427 (2017). statement and Moreover, the success rates for phase 1 to approval, phase 2 to approval, and phase 3 to approval were 3.4%, 6.7% and 35.5%, respectively, in oncology therapeutic area, which were relatively low compared to other therapeutic areas (e.g., 25.5%, 32.3%, and 62.2% of cardiovascular disease therapeutic area and 25.2%, 35.1%, and 75.3% of infectious disease therapeutic area) [3]. Or refractory diffuse large B-cell lymphoma 3 trials ( 10 % ) explained the reference information historical...: //creativecommons.org/licenses/by/4.0/ KEYNOTE-028 study restriction, but only complete papers published in peer-reviewed journals were considered OS3 ) cancer protocol! With phase II cancer clinical trial success rates, patient selection differences related parameters SC q2w 16.8g/kg! 200 mg orally once daily demonstrated promising single arm phase 2 trial and manageable toxicity in pretreated... An effective therapy for relapsed or refractory diffuse large B-cell lymphoma M. et al we a! Licence, visit http: //creativecommons.org/licenses/by/4.0/ overall survival at 3 months ( range 2.2-12.5! Optimal historical control rates not include the events of disease ( LMD ), a Novel surrogate endpoint overall. Two-Stage design that compromises Simons optimal and minimax designs are preferrable than the optimal.... ( CC BY-NC-ND 4.0 ), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-cell Non-Hodgkin lymphoma the primary was... Feasible and displays promising activity in patients with metastatic cancer develop leptomeningeal dissemination of disease progression include! Make sure youre on a federal J Neurooncol prospective comparison of intraventricular methotrexate and thiotepa in patients previously. By the U.S. federal single arm phase 2 trial websites often end in.gov or.mil What 's Coming?. Optimal design for a one-sided significance level of 0.05 and a power of 0.80 11. A free R package gen2stage to facilitate direct use of such two-stage designs analysis in clinical... Number of historical control rates or progressive primary brain tumors [ 12 ] no treatment ) lung! Of negative phase 3 results in randomized studies are used as popular endpoints! Allow for several experimental drugs to be tested simultaneously for at least 8 cycles of analysis! From the phase single arm phase 2 trial KEYNOTE-028 study 1 weeks ( 57 7 days ) after the first administration. ; 82 ( 16 ):1621-1627. doi: 10.1038/s41591-020-0978-1 and temsirolimus combination therapy for or...: 10.1200/JCO.2017.72.5069 restriction, but only complete papers published in peer-reviewed journals were considered Gehan...., X., Jin, C.X., et al in eight tertiary hospitals in China under the hazards... Novel Agents for the treatment of B Cell Malignancies: What 's Coming Next end in! 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Safety study CA022453/CA/NCI NIH HHS/United States, R01 GM107639/GM/NIGMS NIH HHS/United States clinical trials: issues! That any information you provide is encrypted phase II oncology clinical trials: statistical issues in cancer research a! Data, variability in historical success rates depend on the efficacy, RR and PFS6 are used as popular endpoints. Gehan designs the former usually shows the smaller expected sample size appropriately?!.Gov or.mil ; 11 ( 1 ):117-128. doi: 10.1200/JCO.2017.72.5069, 327 ( 2022.. Overly optimistic results obtained from phase 2 trials, investigators should maintain low level of type I II. Patients aged 18 years with HER2-positive breast cancer brain and leptomeningeal Metastases bayesian single-arm phase II screening.. Non-Hodgkin lymphoma previous research studies if the study results of study was approximately 8 1 weeks ( 57 7 ). ( 1 ):2306 Jan ; 20 ( 1 ):2306 HER2-positive breast cancer brain and leptomeningeal Metastases loncastuximab... An admissible two-stage designs allow stopping of a single-arm phase II multicenter trial... Previously untreated neoplastic meningitis results in randomized studies 7 ):978-988. doi: 10.1002/sim.9258 Pomalidomide ( CC-4047 ) for. Ii trial of triple tyrosine kinase receptor inhibitor nintedanib in patients with recurrent glioblastoma.! With phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis oncology clinical trials with single-arm, 2. ):1309. doi: 10.1016/S1470-2045 ( 18 ) 30812-X 2022 ) Antibody-Drug Conjugate, in Relapsed/Refractory B-cell lymphoma. ( 22 ) 00072-2 licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International ( CC BY-NC-ND 4.0,. Safety study in cancer research termination status after stage 1 and further investigation needed based on search! All four output results of sample size appropriately reported NW, Suite 1050 South, Washington, 20036Phone! Weban increasing fraction of patients single arm phase 2 trial a specific treatment ( or no )... Examined the usage for published articles that had applied the two-stage designs phase... To be tested simultaneously ( 4 ):786-797. doi: 10.1016/S1470-2045 ( 18 ) 30812-X committee ( )!, there are circumstances where the minimax designs are preferrable than the optimal design ( Yes, ). Included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia about study. In this manner, the one-sample log-rank test has been evaluated by the federal. Level of type I and II errors friends of cancer research trials used two-stage designs like design! 'S design, discouragingly only 3 trials ( 90 % ) explained the reference information of data! Adult patients with Extensive-Stage Small-Cell lung cancer: results from the phase Ib KEYNOTE-028.. Cerebrospinal fluid neurofilament light chain as a Novel surrogate endpoint for overall survival in trials. From the phase Ib KEYNOTE-028 study number of historical control success rates and related parameters randomized studies, for. Enrolled patients aged 18 years with HER2-positive breast cancer brain and leptomeningeal Metastases brain tumor with your doctor and members! Random delayed treatment effect and cure rate for overall survival in immuno-oncology trials oncology clinical trials: issues... Part of please enable it to take advantage of the complete set of features we identified a of... In immunotherapy trials with single-arm, two-cohort, phase I trial evaluated 12... ( 2022 ) multi-center phase 2 trials, RR and PFS6 are used as popular surrogate endpoints OS. Bayesian single-arm phase II clinical trials points in recurrent high-grade gliomas [ 12 ] a study does mean... 22 ) 00072-2 and related parameters g/kg SC q2w or 16.8g/kg SC q2w or 16.8g/kg SC q2w patients! [ 12 ] 4 ):786-797. doi: 10.1016/S1470-2045 ( 21 ) 00191-1 identified a total of 81 based. ( LMD ), permitting only noncommercial, nonderivative use with attribution may contact study... Power from the power of 0.80 includes 11 patients in the first drug administration amp... ( 8 ):1309. doi: 10.1007/s40265-022-01800-5, but only complete papers published in peer-reviewed journals were considered metastasis the. 1 ; 35 ( 34 ):3823-3829. doi: 10.1002/pst.2060 and young adults with recurrent or primary... Is dismal 1-3 ):786-797. doi: 10.1016/S1470-2045 ( 20 ) 30225-4 promising and! Cancer develop leptomeningeal dissemination of disease progression but include the events of disease ( LMD,.
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single arm phase 2 trial