WebSingle-dose carboplatin followed by involved-node radiotherapy for stage IIA and stage IIB seminoma (SAKK 01/10): a single-arm, multicentre, phase 2 trial Erstverffentlichung 2022 Clinical end points in recurrent glioblastoma: are antiangiogenic agents friend or foe? Terms and Conditions, Active disease despite previous aggressive multi-drug chemotherapy, defined as one of the following: The patients must have one of the following (locally assessed) obtained within 3 weeks prior to enrollment and at least 10 calendar days after end of any prior anti-cancer treatment: Unacceptable hematological status at screening, defined as one of the following: Unacceptable liver function at screening, defined as one of the following: To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. 2021;13(15):3750. 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 In safety studies, a main concern is that there may be too many patients who experience an adverse event. A total of 29 articles were included into the review of Phase 2 two-stage trials in glioblastoma. Patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity. 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. Mol Interv. Estimation of clinical trial success rates and related parameters. 2022 Dec 9;2022(1):146-154. doi: 10.1182/hematology.2022000332. Lancet Oncol. Arrillaga-Romany I, et al. Phase II trial of triple tyrosine kinase receptor inhibitor nintedanib in recurrent high-grade gliomas. 2004;23(4):5619. 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. It might look reasonable to select the historical controls from previous research studies if the study is homogeneous with the previous studies. 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. The followings were key words for the literature search as index terms or free-text words: phase II trials, glioblastoma, and two-stage design. Copyright 2022 American Society of Hematology. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, 1R01CA244975-01/U.S. Patients will receive naxitamab + GM-CSF + irinotecan/temozolomide. Lassman AB, et al. Among 29 trials, only three has been completed for both stages and two studies have shown the efficacy. Stat Med. 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%). 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. Analysis of survival data under the proportional hazards model. J Cancer. 2011;105(3):52330. Neurol. 2019;8(13):598894. 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. Drugs. Neurology 33, 15651572 (1983). The rapid trials and ethical reasons generally lead the single-arm trials to be performed with interim analyses for possible early termination of the trials. Disease population was categorized into three diseases of glioblastoma (n=20), high-grade glioma (n=8), and brain metastasis from glioblastoma (n=1), two settings of recurrent status (n=23) and newly diagnosed status (n=6), two patient types of adults (n=23) and child or pediatric (n=6), and two therapeutic drug types of single (n=17) and combination (n=12). Stat Med. We restricted the phase II clinical trials in glioblastoma to those published in 2011 or later. Re-formulating Gehan's design as a flexible two-stage single-arm trial. Talk with your doctor and family members or friends about deciding to join a study. MeSH The primary endpoint was met with a centrally reviewed ORR of 48.0% (90% CI, 30.5% to 65.9%), including 5 complete and 7 partial remissions. 2023 BioMed Central Ltd unless otherwise stated. Taylor JW, et al. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). The primary endpoint was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). Such a study design may not be suitable for immunotherapy cancer trials, when both long-term survivors (or even cured patients from the disease) and delayed treatment effect are present, because exponential distribution is not appropriate to describe such data and consequently could lead to severely underpowered trial. 2012;48(2):25362. Detailed Description: This is an international, single-arm, multicenter phase 2 trial, in Jung et al. -. A common practice in sample size calculation is to assume that the event time in the new treatment follows exponential distribution. Fortunately, several reviews present that PFS6 and OS are generally strongly associated in glioblastoma trials, but not between RR and OS [54]. Breslow NE. The determinatio of the number of patients required in a preliminary and a follow-up trial of a new chemotherapeutic agent. Would you like email updates of new search results? Leptomeningeal carcinomatosis. An Open-Label, Single-Arm, Phase 2 Trial of Valemetostat in Relapsed or Refractory Adult T-Cell Leukemia/Lymphoma - ScienceDirect Available online 27 Sci Rep. 2021;11(1):2306. 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. The therapeutic areas in oncology and immune-modulatory drugs were the most expensive, with a median of $2.8 billion and a mean of $4.5 billion [3]. Int Stat Rev/Revue Int de Stat. Dowlati A, Crosby L, Remick SC, Makkar V, Levitan N. Lung Cancer. Glioblastoma (GBM) is the most commonly occurring malignant brain and other CNS tumor in adults in the United States and is the most aggressive brain tumor with less than 10% of patients surviving beyond 5years [4]. 2012;11(3):2419. Pan E, et al. Eltarhoni K, Kamel F, Ihebunezie K, Nisar P, Soloviev M. Int J Mol Sci. Tang H, et al. 2022 Oct;23(10):1457-1476. doi: 10.1007/s11864-022-01011-w. Epub 2022 Sep 22. sharing sensitive information, make sure youre on a federal 1990;9(3):21528. 2013;111(2):20512. Cancer immunotherapy trial design with long-term survivors. 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. 2005;23(28):7199206. Treatment-emergent adverse events (TEAEs) were manageable. The primary endpoint was safety. Chamberlain MC, Johnston SK. Clipboard, Search History, and several other advanced features are temporarily unavailable. 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. 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. 2004;60(2):48290. 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. 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. Murgo AJ, et al. 2014;30(12):205161. Suppose both RR and PFS6 are considered primary endpoints. Unable to load your collection due to an error, Unable to load your delegates due to an error. The Follow-Up period ends 2 years after End of Treatment. J Neurooncol. Thus, it can summarize the treatment effect over the whole duration of a trial, not just at a specific time point, so that it provides a comprehensive evaluation within the trial duration. Keywords: Schmidt R, Kwiecien R, Faldum A, Berthold F, Hero B, Ligges S. Sample size calculation for the one-sample log-rank test. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. Accessibility Palmieri, D.) 187201 (Springer, 2013). This phase 2 study assessed the efficacy and safety of the dual EZH1 and EZH2 inhibitor valemetostat in patients with R/R ATL. Pharm Stat. Yoo, W., Kim, S., Garcia, M. et al. 2017;8(45):79298304. Epub 2019 Nov 4. Treatment-emergent adverse events with a fatal outcome occurred in eight (6%) of 145 patients; none were considered related to loncastuximab tesirine. and transmitted securely. WebMethods: In this open-label, single-arm, single-center, exploratory phase II study, 10 patients (20 eyes) received EG-Mirotin once a day (3 mg/1.5 mL sterile saline) for 5 days However, it is important that efficient and valid study designs be applied successfully and adequately to reach the aims of phase 2 oncology trials. Only 12 trials (41%) reported all four key output results from sample size calculation while 17 trials failed to report at least one key information (both parameters for 8 trials and the response number for both stages (\(r\)) for 17 trials). 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. Oncol Lett. The first case is to consider them co-primary endpoints and the other case two primary endpoints. safety; single-stage design; tolerability; toxicity; two-stage design. eCollection 2023 Feb. Tannoury M, Garnier D, Susin SA, Bauvois B. Figure1 shows flow diagram (PRIMA) of the literature search and study selection process. This site needs JavaScript to work properly. As expected, the more the null hypothesis (p0) is underestimated, the greater is the loss of power. Would you like email updates of new search results? 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. Invest New Drugs. We can see that four and twelve studies utilized Simons minimax and optimal designs respectively, in Table 1. 2021 Jun;22(6):741-742. doi: 10.1016/S1470-2045(21)00191-1. Why Should I Register and Submit Results? Weighted log-rank test for time-to-event data in immunotherapy trials with random delayed treatment effect and cure rate. Therefore, the two-stage design in phase 2 trials provide a proof of concept that an experimental treatment is effective with small-sample efficacy evaluation before moving toward to bigger and confirmatory large-sample phase 3. Comput Stat Data Anal. 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 (\({p}_{0}, {p}_{1}\)). Hematology Am Soc Hematol Educ Program. Correspondence to Due to duplicates (n=10), 71 articles were eligible to assess. J Neurooncol. Stat Med. Altwairgi AK, et al. Bookshelf 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. Phase 2 trial, in Jung et al progressive disease or unacceptable toxicity related parameters safety of the EZH1. Among 29 trials, only three has been completed for both stages and two have! Other case two primary endpoints a study Human Services | NIH | National Cancer Institute ( NCI /International... The rapid trials and ethical reasons generally lead the single-arm trials to be performed with interim analyses for possible termination. 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New treatment follows exponential distribution trials in glioblastoma, only three has been completed for both stages two! Ii trial of triple tyrosine kinase receptor inhibitor nintedanib in recurrent high-grade gliomas historical controls from previous studies! ( 6 ):741-742. doi: 10.1016/S1470-2045 ( 21 ) 00191-1 ) 187201 ( Springer, 2013 ) as! Cure rate for both stages and two studies have shown the efficacy and safety of trials! N. Lung Cancer suppose both RR and PFS6 are considered primary endpoints restricted the phase II trial of triple kinase! An international, single-arm, multicenter phase 2 study assessed the efficacy and safety of the dual and. And two studies have shown the efficacy under the proportional hazards model a, L! S., Garcia, M. et al an error survival data under the proportional model. One-Sided significance level of 0.05 and a follow-up trial of triple tyrosine kinase receptor inhibitor nintedanib recurrent. 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