2013 May;139(1):13-22. doi: 10.1007/s10549-013-2525-y. Oncol Lett. Phase 2 study of Pomalidomide (CC-4047) monotherapy for children and young adults with recurrent or progressive primary brain tumors. Please enable it to take advantage of the complete set of features! Epub 2021 Nov 15. The author(s) read and approved the final manuscript. An official website of the United States government. Glioblastoma: emerging treatments and novel trial designs. Bayesian hierarchical modeling of patient subpopulations: efficient designs of Phase II oncology clinical trials. The outcomes of simulation are depicted in Fig. Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis. doi: 10.1371/journal.pone.0271094. Expert Rev Anticancer Ther. 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. FOIA Please enable it to take advantage of the complete set of features! Optimal two-stage designs for exploratory basket trials. DU reports personal fees from ADC Therapeutics, during the conduct of the study; and has a patent (20200171164) pending. 11, 561569 (1993). Here, we performed a complete systematic review on the phase 2 single-arm two-stage trials in glioblastoma to evaluate the appropriate application of the two-stage designs. sharing sensitive information, make sure youre on a federal Alternatively, novel surrogates can be used instead of RR and PFS6. Epub 2019 Feb 11. 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 And 7 trials were used with (1) 5% and 20% (2) 10% and 10% as their type 1 and 2 errors respectively. 2022;14(3):28394. Brastianos PK, Lee EQ, Cohen JV, Tolaney SM, Lin NU, Wang N, Chukwueke U, White MD, Nayyar N, Kim A, Alvarez-Breckenridge C, Krop I, Mahar MK, Bertalan MS, Shaw B, Mora JL, Goss N, Subramanian M, Nayak L, Dietrich J, Forst DA, Nahed BV, Batchelor TT, Shih HA, Gerstner ER, Moy B, Lawrence D, Giobbie-Hurder A, Carter SL, Oh K, Cahill DP, Sullivan RJ. In the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. 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. Experimental: Naxitamab and GM-CSF in combination with irinotecan and temozolomide, 12 Months and older (Child, Adult, Older Adult). In these cases, researchers must use endpoints like response ratethat can demonstrate clinical impact in the absence of direct comparison data. Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma. When the sample size is limited, one can use the Bayesian optimal design for phase II clinical trials, in which the power will be maximized given the fixed sample size and choice of type I error rate [51]. eCollection 2023 Feb. Tannoury M, Garnier D, Susin SA, Bauvois B. Bayesian single-arm phase II trial designs with time-to-event endpoints. Diagnosis and treatment patterns for patients with leptomeningeal metastasis from solid tumors across Europe. Santoni M, et al. Part of Let us assume that the result of a two-stage design indicates 18 and 23 in total patients for the minimax and optimal respectively. sharing sensitive information, make sure youre on a federal Cancer immunotherapy trial design with cure rate and delayed treatment effect. 1800 M Street NW, Suite 1050 South,Washington, DC 20036Phone: (202) 944-6700. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. Bethesda, MD 20894, Web Policies J Neurooncol. 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)? Regardless that more than 75% trials mentioned all key input parameters, many studies (17/29, 59%) failed to provide at least one key output of sample size calculation results of the number of samples of both stages (\({n}_{1}, n\)) and the treatment rejection numbers of the first stage and both stages (\({r}_{1}, r\)). An official website of the United States government. Unable to load your collection due to an error, Unable to load your delegates due to an error. Stat Med. FOIA Lassen U, et al. 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. Oncol. Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. 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. 4). Flow diagram (PRIMA) of the literature search and study selection process. 2013;24(4):11129. Studies a U.S. FDA-regulated Drug Product: Studies a U.S. FDA-regulated Device Product: Irinotecan, solution for infusion (20 mg/mL), Temozolomide, capsules (5 mg, 20 mg and 100 mg), The humanized immunoglobulin isotype G (IgG1) monoclonal antibody (mAb) naxitamab, solution for infusion (4 mg/mL), Sargramostim (GM-CSF), lyophilized 250 g single use vial (250 g/vial), Overall response rate (ORR) [TimeFrame:84 days], ORR after 2 cycles [TimeFrame:42 days], Duration of response (DoR) [TimeFrame:2 years], Complete response (CR) rate [TimeFrame:84 days], Time to first subsequent therapy [TimeFrame:3 years], Progression free survival (PFS) [TimeFrame:3 years], Overall survival (OS) [TimeFrame:3 years], Overall survival (OS) [TimeFrame:1 year], Overall survival (OS) at 2 years [TimeFrame:2 year], Receipt of Standard of Care (SoC) frontline induction/consolidation therapy (including surgery, chemotherapy, ASCT, MIBG, radiotherapy, immunotherapy, or retinoids), verified first progression during multi-drug frontline treatment or, verified first episode of relapse, defined as recurrence after response to frontline treatment, or, verified first designation of refractory disease, defined as persistent metastatic disease (SD or minor response by INRC and MIBG curie score 3) detected at conclusion of at least 4 cycles of multi-drug induction chemotherapy on or according to a high-risk NB treatment protocol as defined above, Measurable tumor on CT/MRI scan that is MIBG-avid or demonstrates increased FDG uptake on PET scan, MIBG (Metaiodobenzylguanidine) scan with positive uptake at a minimum of one site. A Simon two-stage design was used to compare a null hypothesis OS3 of 18% against an alternative of 43%. https://doi.org/10.1186/s12874-022-01810-7, DOI: https://doi.org/10.1186/s12874-022-01810-7. This site needs JavaScript to work properly. The optimal design usually recommended over the minimax design because the former usually shows the smaller expected sample size [12]. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. Sharma M, et al. Clin Trials. 2021;20(6):123548. Such an unexpected situation cannot be appropriately handled with the current system of two-stage designs because current designs require to prespecify the design information like sample size for each stage and stopping rules in the study protocol. Eur J Cancer. All authors reviewed the manuscript. J Neurooncol. Bookshelf WY, SK, and MG wrote the main manuscript text and WY and SK prepared Table 1 and Figs. 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. 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. 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. Epub 2022 Aug 10. Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. Eltarhoni K, Kamel F, Ihebunezie K, Nisar P, Soloviev M. Int J Mol Sci. 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]. Google Scholar. Lancet Oncol. 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. Arrillaga-Romany I, et al. The determinatio of the number of patients required in a preliminary and a follow-up trial of a new chemotherapeutic agent. Phase II trials in journal of clinical oncology. Adaptive two-stage designs for single-arm phase IIA cancer clinical trials. Epub 2022 Apr 1. Neuro Oncol. Disclaimer, National Library of Medicine Epub 2020 Sep 1. 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. Accessibility 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. Cancer 124, 2135 (2018). Google Scholar. Epub 2015 Apr 1. 2021 Feb 8;16(2):e0246448. For instance, in Case 3, the 10% and 50% reductions of p0 are 0.45 (=0.50.9) and 0.25 (=0.50.5). A common practice in sample size calculation is to assume that the event time in the new treatment follows exponential distribution. 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. Figure2 summarized frequencies and proportions from identified ten topics related Phase 2 single-arm two-stage designs: (1) disease (Yes: GBM, No: glioma), (2) setting (Yes: recurrent, No: newly-diagnosed), (3) patients (Yes: adults, No: child), (4) therapeutic drug (Yes: single, No: combination), (5) primary endpoint (Yes: PFS6, No: ORR and others), (6) methods of two-stage sign (Yes: Simon, No: others), (7) all four key input information of two-stage design provided? Using four key input parameters of two types of error (\(\alpha , \beta\)) and two hypothesis rates of unacceptable maximum response rate of historical control (\({p}_{0}\)) and acceptable minimum response rate of study expectation (\({p}_{1}\)), we can implement the sample size calculation of the two-stage designs. Stat Med. Blood 2022; blood.2022016862. 2001 May;32(2):155-62. doi: 10.1016/s0169-5002(00)00220-8. Their composite endpoint model provides efficiency while still maintaining the clinical relevance of OS. WebTOCIVID-19 trial is registered in the EudraCT database with number 2020-001110-38 and in clinicaltrials.gov with ID NCT04317092. This work was supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute. 2017;8(45):79298304. Furthermore, all trials except one trial did not explain how they chose the acceptable response rate. 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). You have reached the maximum number of saved studies (100). Stat Med. Nat Commun. In this case, there are two ways to incorporate two endpoints into the trial design. Findings: Between March 30, 2015, and Aug 3, 2018, 79 patients were enrolled. A phase 2 study of the first imipridone ONC201, a selective DRD2 antagonist for oncology, administered every three weeks in recurrent glioblastoma. Wang Z-X, et al. Phase 0 clinical trials: recommendations from the task force on methodology for the development of innovative cancer therapies. Rubinstein LV, et al. The primary endpoint was safety. Leptomeningeal carcinomatosis. Due to duplicates (n=10), 71 articles were eligible to assess. Murgo AJ, et al. Before Valemetostat 200 mg orally once WebRandomized and Single-Arm Trials An arm of a clinical trial is a group of patients receiving a specific treatment (or no treatment). Ipilimumab and single arm phase 2 trial in leptomeningeal carcinomatosis new chemotherapeutic agent Child, Adult, older Adult ) May... Modeling of patient subpopulations: efficient designs of phase II trial designs with time-to-event endpoints number of studies... Of ipilimumab and nivolumab in leptomeningeal carcinomatosis study ; and has a patent ( 20200171164 pending. Sharing sensitive information, make sure youre on a federal Alternatively, novel surrogates can be used of! 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And Catherine Ivy Foundation and Barrow Neurological Institute information, make sure youre on federal... For children and young adults with recurrent or progressive primary brain tumors make sure youre a! Trial did not explain how they chose the acceptable response rate take advantage of the literature search study.: https: //doi.org/10.1186/s12874-022-01810-7, doi: https: //doi.org/10.1186/s12874-022-01810-7 trial of a single-arm phase IIA cancer trial. P, Soloviev M. Int J Mol Sci ) monotherapy for children young! Nisar P, Soloviev M. Int J Mol Sci 2001 May ; 32 ( 2 ):155-62.:!, Ihebunezie K, Nisar P, Soloviev M. Int J Mol Sci and Barrow Neurological Institute follow-up trial a..., there are two ways to incorporate two endpoints into the trial design time-to-event endpoints across Europe ).! Cc-4047 ) monotherapy for children and young adults with recurrent or progressive primary brain tumors chose the acceptable rate... Except one trial did not explain how they chose the acceptable response rate in these,., researchers must use endpoints like response ratethat can demonstrate clinical impact in the new treatment follows exponential.... Trial, the one-sample log-rank test has been frequently used a patent ( 20200171164 ).! Intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis recurrent or primary. Primary brain tumors: 10.1007/s10549-013-2525-y rate and delayed treatment effect to incorporate endpoints!
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