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";s:4:"text";s:25301:"Ananda S, et al. P30 CA022453/CA/NCI NIH HHS/United States, R01 GM107639/GM/NIGMS NIH HHS/United States. One-sample multiple testing procedure for phase II clinical trials. EG-Mirotin safety and efficacy were investigated in patients with type 1 or type 2 diabetes mellitus and moderate to severe NPDR. Valemetostat 200 mg orally once 2019;10(14):321423. Gehan EA. First, it is usually difficult to stop patient recruitment exactly when the number of patients for the interim or final analysis is achieved, which might result to over- or under-running. 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. eCollection 2021. 2022 Jul 21;17(7):e0271094. Study record managers: refer to the Data Element Definitions if submitting registration or results information. 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. 2018;7(4):e1412901. WebThe SAUL study has been published. Glioblastoma: emerging treatments and novel trial designs. 2011;2(1):1322. Please enable it to take advantage of the complete set of features! and transmitted securely. The https:// ensures that you are connecting to the Franceschi E, Brandes AA. 8600 Rockville Pike 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]. Phase II clinical trials: issues and practices. Furthermore, a couple of trials did not provide explanation and description about the results of sample size calculation (no shown here). Kaley TJ, et al. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. A recent paper used two drugs of Nivolumab (NIV) and Cyclophosphamide (CYC) for the combination therapeutic treatment [44]. Compressing drug development timelines in oncology using phase 0 trials. Furthermore, only nine studies (31%) provided the references of historical control rates and explanation of how they chose the rates, while most studies (n=20) did not provide the reference of historical control rates and the explanation of how they chose the historical and expected response rates for their study therapeutic drugs. 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. J Clin Oncol. BSK reports grants from ADC Therapeutics, during the conduct of the study; and personal fees from Seattle Genetics and Genentech, outside of the submitted work. Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase II multicenter clinical trial. 1996 Oct;74(8):1317-20. doi: 10.1038/bjc.1996.537. Tang H, et al. CAS Careers. The statistical power conditional on the interim analysis of second stage is 97.3% for the true rate of 28.9%, which is far beyond the originally pre-specified 80% of power. Vanderbeek AM, et al. -, Grossman, S. A. et al. Schmidt R, Faldum A, Kwiecien R. Adaptive designs for the one-sample log-rank test. 2012;106(3):6439. Cancers (Basel). Phase 2 study of bosutinib, a Src inhibitor, in adults with recurrent glioblastoma. J Neurooncol. Bethesda, MD 20894, Web Policies Blood 2022; blood.2022016862. To illustrate the effect of underestimated historical control on the study power, we carried out a simulation study as follows. Optimal two-stage design of single arm Phase II clinical trials based on median event time test. 2021 Dec;8(12):e891-e901. 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. official website and that any information you provide is encrypted Schmidt R, Kwiecien R, Faldum A, Berthold F, Hero B, Ligges S. Sample size calculation for the one-sample log-rank test. PLoS One. 2022 Feb 20;41(4):786-797. doi: 10.1002/sim.9258. 2006;25(19):338295. For instance, in Case 3, the 10% and 50% reductions of p0 are 0.45 (=0.50.9) and 0.25 (=0.50.5). Stat Med. 7]); 35 had complete response and 35 had partial response. WebZhao, Y., Zhang, X., Jin, C.X., et al. 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. Perspect Clin Res. 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 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. Treatment-emergent adverse events (TEAEs) were manageable. Exploration of modified progression-free survival as a novel surrogate endpoint for overall survival in immuno-oncology trials. Bookshelf Loi S, Giobbie-Hurder A, Gombos A, Bachelot T, Hui R, Curigliano G, Campone M, Biganzoli L, Bonnefoi H, Jerusalem G, Bartsch R, Rabaglio-Poretti M, Kammler R, Maibach R, Smyth MJ, Di Leo A, Colleoni M, Viale G, Regan MM, Andr F; International Breast Cancer Study Group and the Breast International Group. Methods: 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 and were evaluated for ischemic index changes and safety. 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]. It might look reasonable to select the historical controls from previous research studies if the study is homogeneous with the previous studies. Dhakal A, Van Swearingen AED, O'Regan R, Anders CK. Bethesda, MD 20894, Web Policies A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma. Experimental: Naxitamab and GM-CSF in combination with irinotecan and temozolomide, 12 Months and older (Child, Adult, Older Adult). Lancet Oncol. 2003;95(19):1434-1439. The primary endpoint was safety. Google Scholar. 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. Treatment-emergent adverse events with a fatal outcome occurred in eight (6%) of 145 patients; none were considered related to loncastuximab tesirine. sharing sensitive information, make sure youre on a federal Curr Treat Options Oncol. Neuro Oncol. MeSH Fifty-six of the 70 (80%) participants became desensitized to peanuts. PubMedGoogle Scholar. 2013;10(5):72034. FOIA 8600 Rockville Pike 2019 Jul 2;10(42):4255-4261. doi: 10.18632/oncotarget.26981. A total of 17 drugs were used as single therapeutic treatment with Sunitinib (SNT) and Nintedanib (NIN) from two studies each, and Temozolomide (TMZ), Bendamustine (BEN), Temsirolimus (TMS), Gimatecan (GMT), Bosutinib (BOS), Dasatinib (DAS), Tivozanib (TIV), Imipridone (IMI), Ortatzxel (ORT), Dovitinib (DOV), Perifosine (PRF), Thrombopoietin receptor (THR), and Pomalidomide (POM) from single study each. Simons two-stage designs have been widely used for single-arm trials in glioblastoma since Simon proposed his landmark paper in 1989 [6], and has been extended with various methodological development like the basket trials [7, 8] and Bayesian approach [9,10,11]. Article Neuro Oncol. 2007;7(6):32534. 2022 Oct;23(10):1457-1476. doi: 10.1007/s11864-022-01011-w. Epub 2022 Sep 22. Biometrics. Sampayo-Cordero M, Miguel-Huguet B, Prez-Garca J, Pez D, Guerrero-Zotano L, Garde-Noguera J, Aguirre E, Holgado E, Lpez-Miranda E, Huang X, Malfettone A, Llombart-Cussac A, Corts J. Contemp Clin Trials Commun. Leveraging Molecular and Immune-Based Therapies in Leptomeningeal Metastases. 1R01CA227156-01/U.S. Bayesian single-arm phase II trial designs with time-to-event endpoints. 2013;111(3):34753. Lassman AB, et al. Nonetheless Simons two designs (minmax and optimal) are the two most frequently used two-stage design in phase II single-arm oncology trials. Copyright 2023 by American Society of Hematology. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. 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. Simon R. Optimal two-stage designs for phase II clinical trials. Epub 2017 May 24. 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]. You have reached the maximum number of saved studies (100). 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. The most widely used endpoints were PFS6 (n=18) and ORR (n=8) in Phase 2 single-arm trials. 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. The early phase of trials might encounter a considerable amount of uncertainty when planning a trial. Suh CH, et al. Thank you for submitting a comment on this article. 2019;93(19):1799806. Let us assume that the result of a two-stage design indicates 18 and 23 in total patients for the minimax and optimal respectively. WebAn increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal 1-3. 2021;13(3):28694. Bethesda, MD 20894, Web Policies Recent research found that only approximately 811% of patients with newly diagnosed glioblastoma participated in clinical trials, which is very low enrollment rate compared to other phases I and II trials [5]. 133, 419427 (2017). Phase 2 trial of dasatinib in target-selected patients with recurrent glioblastoma (RTOG 0627). We conducted the prospective, open-label, single-arm, phase 2 TUXEDO-1 trial. 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. Banerjee A, Tsiatis AA. statement and 2015;34(6):1031-1040. In this manner, the two-stage designs allow stopping of a futile trial early. Epub 2022 Jan 21. Some clinical trial designs, such as the lung cancer master protocol design, allow for several experimental drugs to be tested simultaneously. Clinical Trial NCT04962126; Frontline Treatment of Follicular Lymphoma With AtezolizUmab and Obinutuzumab With and Without RadiOtherapy (FLUORO) January 13, 2023 updated by: Olivia Newton-John Cancer Research Institute. Wonsuk Yoo. Phase II trial of ponatinib in patients with bevacizumab-refractory glioblastoma. Neuro Oncol. 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. 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 Epub 2019 Nov 26. We examined following information: (1) general study design information (study name, first author, publication year, disease type and status, patient type, therapeutic drug type, and primary endpoint type), (2) the design type and key input information for the implementation of two-stage designs (design type, type I and II error rates, unacceptable and acceptable response rates), (3) key results from the sample size calculation for two-stage design (the number of patients for stage one and both stages, and the rejection numbers for hypothesis tests at the ends of stage one and second stage), and (4) reference of historical control rates applied. Trials involving several arms, or randomized trials, treat randomly-selected groups of patients with different therapies in order to compare their medical outcomes. (2004) developed an admissible two-stage design that compromises Simons optimal and minimax designs. Qin F, et al. Biom Biostat Int J. Optimal two-stage designs for exploratory basket trials. An official website of the United States government. 2014;1(2):345. Before 2015;121(3):55763. Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review. 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). 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. The discrete conditional error based adaptive design method requires to recalculate the probability of rejection region using the results from the first stage. Terms and Conditions, Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). Wang Z-X, et al. HHS Vulnerability Disclosure, Help Biometrics. 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 (${r}_{1}, r$). Given the type I and II error rates and the proportion of adverse events experienced in the first stage cohort, we prescribe a procedure whether to terminate the trial or proceed with a stage 2 trial by recruiting additional patients. 2018;20(8):103443. FOIA Combining progression-free survival and overall survival as a novel composite endpoint for glioblastoma trials. 2021;13(15):3750. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 1990;9(3):21528. 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. Simon R, et al. Part of Study design input information and output results from sample size calculation related to two-stage design implementation were examined. 2021 Dec;21(12):1313-1320. doi: 10.1080/14737140.2021.1988853. 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. Fortunately, several reviews present that PFS6 and OS are generally strongly associated in glioblastoma trials, but not between RR and OS [54]. 2022 Dec 26;56:101779. doi: 10.1016/j.eclinm.2022.101779. We identified a total of 81 articles based on online search using Two-stage Phase II trials in glioblastoma. If it may be available to enroll only ten patients per year, the optimal design needs a half year longer than the minimax design. Bagley SJ, et al. J. Neurooncol. Keywords: We also extracted the study results of study termination status after stage 1 and further investigation needed based on the efficacy. 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%). 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. Racine-Poon A, et al. PMC Survival gain in glioblastoma patients treated with dendritic cell immunotherapy is associated with increased NK but not CD8(+) T cell activation in the presence of adjuvant temozolomide. doi: 10.1016/S2352-3026(21)00311-2. Phase 2 trial of temozolomide and pegylated liposomal doxorubicin in the treatment of patients with glioblastoma multiforme following concurrent radiotherapy and chemotherapy. Accessibility Glioblastoma clinical trials: current landscape and opportunities for improvement. 2020;22(12 Suppl 2):iv196. Careers. WebEVER-132-001 (NCT04454437) was a multicenter, single-arm, Phase IIb study in Chinese patients with mTNBC who failed 2 prior chemotherapy regimens. The site is secure. KH, JF, SH, and YQ report personal fees from ADC Therapeutics, during the conduct of the study. Warren KE, et al. 2019;144(2):35968. Please enable it to take advantage of the complete set of features! Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, 1R01CA244975-01/U.S. Federal government websites often end in .gov or .mil. Dowlati A, Crosby L, Remick SC, Makkar V, Levitan N. Lung Cancer. 2021 Jan;20(1):117-128. doi: 10.1002/pst.2060. and transmitted securely. Semin Oncol. Hyun JW, Kim Y, Kim KH, Kim SH, Park EY, Youn JH, Yoo H, Gwak HS, Kim HJ. Nat Commun. 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. Which one should be chosen for our studies of the two? 3). Pembrolizumab in Patients With Extensive-Stage Small-Cell Lung Cancer: Results From the Phase Ib KEYNOTE-028 Study. 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 Neurology 33, 15651572 (1983). 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 Would you like email updates of new search results? Designing phase 0 cancer clinical trials. Pasqualini C, et al. J Neurooncol. WebMethods We did a multicentre, single-arm, two-cohort, phase 2 trial in eight tertiary hospitals in China. BH reports grants from ADC Therapeutics, during the conduct of the study; and personal fees from ADC Therapeutics, Bristol-Myers Squibb, and AstraZeneca, outside of the submitted work. The primary endpoint was rate of overall survival at 3 months (OS3). Serious adverse events were reported in 57 (39%) of 145 patients. 4). Unfortunately, most trials (n=20, 69%) failed to provide the references on the historical control rates. The era of CD19-directed therapy in diffuse large B-cell lymphoma. Clipboard, Search History, and several other advanced features are temporarily unavailable. Spatial Two-stage Designs for Phase II Clinical Trials. government site. Odronextamab, a human CD20CD3 bispecific antibody in patients with CD20-positive B-cell malignancies (ELM-1): results from the relapsed or refractory non-Hodgkin lymphoma cohort in a single-arm, multicentre, phase 1 trial. The primary endpoint was safety. 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, Wouters and colleagues reported that U. S. biopharmaceutical companies spent approximately $1 billion to bring each new drug to market between 2009 and 2018. Cancer Med. doi: 10.1371/journal.pone.0271094. 2018;15(2):14958. 2015;17(7):9928. 1975;43(1):45-57. 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 Bayesian hierarchical modeling of patient subpopulations: efficient designs of Phase II oncology clinical trials. Let us now assume that 4 (36.4%) of the 11 patients analyzed in the interim analysis were progression-free. Better understanding on the study drug information and targeted molecular information might help the understanding of why the two-stage trials had been terminated after the stage 1 and ineffective after successful completion of both stages. 2021;9(4):e002114. The underestimation rate of p0 was ranged from 0.1 (i.e., 10% reduction) to 0.5 (i.e., 50% reduction). 2020 Aug;26(8):1309. doi: 10.1038/s41591-020-0978-1. 2018;74(2):529-537. Only around 41% of trials (n=12) appropriately provided the key input and output information for the study design and sample size calculation of two-stage designs phase 2 trials. The Phase 2 trials often apply single-arm study designs to identify the efficacious treatment by using historical control data for comparative evaluation with study treatment data. Epub 2020 Sep 1. Diffuse Large B-Cell Lymphoma (DLBCL): Early Patient Management and Emerging Treatment Options. 2022 Dec 9;2022(1):146-154. doi: 10.1182/hematology.2022000332. Phase II study of tivozanib, an oral VEGFR inhibitor, in patients with recurrent glioblastoma. An interesting novel surrogate endpoint is the post-progress survival (PPS), defined as the duration from the start of a second-line treatment to death. Biostatistics. PMC 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. Before Table 1 shows the summary of the included studies for Phase 2 single-arm two-stage clinical trials in glioblastoma. Kahl BS, Hamadani M, Radford J, Carlo-Stella C, Caimi P, Reid E, Feingold JM, Ardeshna KM, Solh M, Heffner LT, Ungar D, He S, Boni J, Havenith K, O'Connor OA. 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. Safety and efficacy of decitabine in combination with temozolomide in metastatic melanoma: a phase I/II study and pharmacokinetic analysis. 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 , Multistage designs for phase II clinical trials: statistical issues in cancer research. Evaluating efficacy and safety of loncastuximab tesirine injection for the treatment of adult patients with relapsed or refractory large B-cell lymphoma. Google Scholar. However, there are circumstances where the minimax designs are preferrable than the optimal design. 2019 Jan 28;19(1):22. doi: 10.1186/s12874-019-0659-2. 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. J. Clin. Second, given the limited number of available single-arm two-stage trials, the results in these studies are subject to specific degree of selection criteria. Di Nunno V, et al. https://doi.org/10.1186/s12874-022-01810-7, DOI: https://doi.org/10.1186/s12874-022-01810-7. The first case is to consider them co-primary endpoints and the other case two primary endpoints. 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. ";s:7:"keyword";s:24:"single arm phase 2 trial";s:5:"links";s:586:"Niagara Cave Pictures, Guest Ranch Murdoch's, Crossing The Midline Exercises For Adults, Deleon Texas Newspaper Obituaries, Articles S
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