single arm phase 2 trial raleigh, nc obituaries 2022

The Follow-Up period ends 2 years after End of Treatment. Stat Med. J Neurooncol. 2022 Jul 21;17(7):e0271094. Lassman AB, et al. Reference curve sampling variability in one-sample log-rank tests. Spatial two-stage designs for phase ii clinical trials. J Neurooncol. In the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. PLoS One. Analysis of survival data under the proportional hazards model. Article 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. Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. Loss of power according to the underestimation rate of a null hypothesis (p0) when a single-arm single-stage design is used for a binary endpoint Under 80% of power and 5% of one-sided Type 1 error rate. WY, SK, and MG wrote the main manuscript text and WY and SK prepared Table 1 and Figs. Bayesian hierarchical modeling of patient subpopulations: efficient designs of Phase II oncology clinical trials. Comput Stat Data Anal. Clin Cancer Res. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Schmidt R, Faldum A, Kwiecien R. Adaptive designs for the one-sample log-rank test. Cancer immunotherapy trial design with long-term survivors. Treatment-emergent adverse events (TEAEs) were manageable. Zhou H, Lee JJ, Yuan Y. BOP2: Bayesian optimal design for phase II clinical trials with simple and complex endpoints. Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma. WebA Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants with Previously Treated Glioblastoma or Other Primary Central Nervous System Tumors Harboring Activating FGFR1-3 Alterations (FIGHT-209) Cancer Answer Line 866.223.8100 IRB Study Number 22-1031 Status Recruiting Jung et al. Would you like email updates of new search results? Lee EQ, et al. 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. Oncol Lett. 2011;2(1):1322. PubMedGoogle Scholar. Unable to load your collection due to an error, Unable to load your delegates due to an error. Valemetostat 200 mg orally once daily demonstrated promising efficacy and manageable toxicity in heavily pretreated patients. eCollection 2021. Eastern Cooperative Oncology Group. Bethesda, MD 20894, Web Policies 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. 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]. Stat Biopharma Res. Leveraging Molecular and Immune-Based Therapies in Leptomeningeal Metastases. eCollection 2023 Feb. Tannoury M, Garnier D, Susin SA, Bauvois B. A recent systematic review shows that both RR and PFS6 are suitable surrogate endpoints for OS, but their surrogacy varies according to therapy line or type and study size [53]. 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%). 2019 Mar;20(3):371-382. doi: 10.1016/S1470-2045(18)30812-X. J Neurooncol. HHS Vulnerability Disclosure, Help Searches were conducted using the electronic database of PubMed, Google Scholar and ClinicalTrials.gov for potentially eligible publications from inception by two independent researchers up to May 26, 2022. Intrathecal administration of trastuzumab for the treatment of meningeal carcinomatosis in HER2-positive metastatic breast cancer: a systematic review and pooled analysis. 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. 2011;105(3):52330. 2018 Sep;17(5):541-554. doi: 10.1002/pst.1878. 8600 Rockville Pike 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. 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. Their composite endpoint model provides efficiency while still maintaining the clinical relevance of OS. 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. 2001 May;32(2):155-62. doi: 10.1016/s0169-5002(00)00220-8. Admissible two-stage designs for phase II cancer clinical trials. Weighted log-rank test for time-to-event data in immunotherapy trials with random delayed treatment effect and cure rate. Bagley SJ, et al. Epub 2022 Dec 6. 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. Most trials (90%) used Simons two-stage designs. J Neurooncol. Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next? Epub 2022 Jan 21. 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. This site needs JavaScript to work properly. 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. A better way to avoid the potential issues is to use a hazard ratio (HR). The site is secure. Clipboard, Search History, and several other advanced features are temporarily unavailable. 2004;23(4):5619. 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]. -, Grossman, S. A. et al. Single-arm phase II trial design under parametric cure models. Rubinstein LV, et al. Phase 2 study of bosutinib, a Src inhibitor, in adults with recurrent glioblastoma. Eligible patients received 10 mg/kg SG on Days 1 and 8 of each 21-day treatment cycle, until disease progression/unacceptable toxicity. The primary endpoint was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). Clin Trials. Oncol. Among 29 trials, only three has been completed for both stages and two studies have shown the efficacy. Batista MFFV, Eiriz I, Fitzpatrick A, Le Du F, Braga S, Alpuim Costa D. Breast Care (Basel). The median follow-up of surviving patients was 6.3 months (range, 2.2-12.5 months). Racine-Poon A, et al. 8600 Rockville Pike This single-arm phase II interventional study aims to assess disease response to, and toxicity of, a Kaley TJ, et al. This site needs JavaScript to work properly. 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 CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 20132017. Wong CH, Siah KW, Lo AW. 8600 Rockville Pike How low levels for both errors are low enough to be a good design? Two types of errors (\(\alpha , \beta\)) are key information for all study designs. 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. Several important topics related to the design issues will be followed to handle the design issues by increasing the precision of efficacy from targeted therapeutic trials of Phase 2 two-stage designs in brain tumor. 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. 2019;8(13):598894. 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]. 2020 Aug;26(8):1309. doi: 10.1038/s41591-020-0978-1. Atorvastatin in combination with radiotherapy and temozolomide for glioblastoma: a prospective phase II study. 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. 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%]). In these cases, researchers must use endpoints like response ratethat can demonstrate clinical impact in the absence of direct comparison data. 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. 1975;43(1):45-57. J. Neurooncol. Suppose both RR and PFS6 are considered primary endpoints. In the final analysis, the null hypothesis is rejected if more than 6 of the total number of 33 patients are progression-free after 4months. Wang et al. 2022;14(3):28394. Pellegatta S, et al. Table 1 is the summary of the included studies [18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46]. 1800 M Street NW, Suite 1050 South,Washington, DC 20036Phone: (202) 944-6700. Phase 2 trial of temozolomide and pegylated liposomal doxorubicin in the treatment of patients with glioblastoma multiforme following concurrent radiotherapy and chemotherapy. Unable to load your collection due to an error, Unable to load your delegates due to an error. Biometrics. 3). mPFS does not include the events of disease progression but include the events of death within 3months after randomization. Mol Interv. Publisher Correction: Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. 2020 Mar 15;39(6):698-708. doi: 10.1002/sim.8440. 2007;7(2):1319. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial Summary Di Nunno V, et al. official website and that any information you provide is encrypted This implies that most brain tumor clinical trials are at high risk with great uncertainty in trial outcomes. 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). Bethesda, MD 20894, Web Policies CNS Drugs. The https:// ensures that you are connecting to the The followings were key words for the literature search as index terms or free-text words: phase II trials, glioblastoma, and two-stage design. 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. Lancet Oncol. J Neurooncol. Further investigations are needed to identify which patients with LMD can benefit from pembrolizumab. 14. In this research, we proposed a piecewise proportional hazards cure rate model with random delayed treatment effect to design single-arm phase II immunotherapy cancer trials. 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]. The site is secure. An International, Single-Arm, Multicenter Phase 2 Trial. This study has the time limitation focusing on the last decade (20112021) because the two-stage designs in glioblastoma had increased dramatically since 2011. The determinatio of the number of patients required in a preliminary and a follow-up trial of a new chemotherapeutic agent. Please check for further notifications by email. Ann Oncol. The https:// ensures that you are connecting to the 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. FOIA Berry SM, et al. To illustrate the effect of underestimated historical control on the study power, we carried out a simulation study as follows. 2019;144(2):4037. Altwairgi AK, et al. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. 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 Diffuse Large B-Cell Lymphoma (DLBCL): Early Patient Management and Emerging Treatment Options. eCollection 2022. 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. While Phase 3 trials are frequently randomized in order to provide more precise data on safety and effectiveness outcomes, a Phase 3 trial might use a single arm if a small target population makes conducting a randomized trial impractical. 2015;34(16):240316. Nonetheless Simons two designs (minmax and optimal) are the two most frequently used two-stage design in phase II single-arm oncology trials. 2015;34(6):1031-1040. 2019 Jan 28;19(1):22. doi: 10.1186/s12874-019-0659-2. Chamberlain MC, Johnston SK. Page MJ, et al. 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. and transmitted securely. Unable to load your collection due to an error, Unable to load your delegates due to an error. Study design input information and output results from sample size calculation related to two-stage design implementation were examined. JPA reports personal fees from ADC Therapeutics, OncLive, and Oncinfo, outside of the submitted work; and has an immediate family member who has served on advisory boards from Puma Biotechnology, Inovio Pharmaceuticals, Agios Pharmaceuticals, Forma Therapeutics, and Foundation Medicine. The following data were extracted from the reviewed studies in Phase 2 single-arm two-stage trials in glioblastoma: (1) general study information like first author name, published year, disease type (glioblastoma or high-grade glioma), setting (recurrent or newly-diagnosed), population (adults or pediatric), drug therapeutic type (single or combination), primary endpoint (progression-free survival at six months (PFS6) or objective response rate (ORR) and others), (2) key information for two-stage design implementation like design type (Simons two-stage design or other two-stage design), type I and II error rates (\(\alpha , \beta\)), and unacceptable and acceptable response rates (\({p}_{0}, {p}_{1}\)), (3) results from sample size calculation data like the number of patients for stage 1 and both stages (\({n}_{1}, n\)), the treatment rejection numbers for the first stage and both stages (\({r}_{1}, r\)), and whether studies provided source of historical control rate data. For instance, in Case 3, the 10% and 50% reductions of p0 are 0.45 (=0.50.9) and 0.25 (=0.50.5). 2009;45(5):7416. The other three trials used two-stage designs like Inadmissible design, Fleming and Gehan designs. 2021;9(4):e002114. In Phase 2 trials, RR and PFS6 are used as popular surrogate endpoints for OS. Epub 2021 Oct 17. By using this website, you agree to our The variability must be estimated based on experiences of that institution on multiple studies of other treatment. Ott PA, Elez E, Hiret S, Kim DW, Morosky A, Saraf S, Piperdi B, Mehnert JM. -. There was no language restriction, but only complete papers published in peer-reviewed journals were considered. 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. Muhic A, et al. We identified a total of 81 articles based on online search using Two-stage Phase II trials in glioblastoma. J Chronic Dis. Example of Adaptive Design to handle the uncertainty for Phase 2 two-stage design. 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. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Optimal two-stage design of single arm Phase II clinical trials based on median event time test. 2022 May;9(5):e327-e339. 2015 May-Jun;14(3):226-32. doi: 10.1002/pst.1678. Epub 2017 Aug 16. Manage cookies/Do not sell my data we use in the preference centre. Detailed Description: This is an international, single-arm, multicenter phase 2 trial, in Suppose a two-stage design with a type I error no larger than \({\alpha }^{*}\) and a power no smaller than (1- \({\beta }^{*}\)) for given (\({p}_{0}\), \({p}_{1}\)). OPTIM-ARTSAn adaptive phase II open platform trial design with application to a metastatic melanoma study. 1996 Oct;74(8):1317-20. doi: 10.1038/bjc.1996.537. Clin Trials. 2003;95(19):1434-1439. 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. The primary endpoint was rate of overall survival at 3 months (OS3). Cancers (Basel). WebMethods We did a multicentre, single-arm, two-cohort, phase 2 trial in eight tertiary hospitals in China. 2009;27(19):30736. The followings were key words for the literature search as index terms or free-text words: phase II trials, glioblastoma, and two-stage design. Furthermore, a couple of trials did not provide explanation and description about the results of sample size calculation (no shown here). 2004;60(2):48290. Curr Treat Options Oncol. Epub 2022 Apr 1. Please enable it to take advantage of the complete set of features! Results. Finally, we can calculate the expected sample sizes of \({n}_{1}\) or \(n\) with a true response rate of the experimental therapy since the sample size of \({n}_{1}\) and \(n\) are random variables [6, 12, 17]. Kummar S, et al. Hu J, et al. Your comment will be reviewed and published at the journal's discretion. Federal government websites often end in .gov or .mil. Keywords: We conducted a single-arm, phase 2 study of pembrolizumab in patients with solid tumor malignancies and LMD (NCT02886585). 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). Disclaimer, National Library of Medicine Would you like email updates of new search results? WebEVER-132-001 (NCT04454437) was a multicenter, single-arm, Phase IIb study in Chinese patients with mTNBC who failed 2 prior chemotherapy regimens. The era of CD19-directed therapy in diffuse large B-cell lymphoma. Clipboard, Search History, and several other advanced features are temporarily unavailable. Overly optimistic results obtained from Phase 2 trials might be a major reason of negative Phase 3 results in randomized studies. BMJ. 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. Pharm Stat. Single-arm or non-randomized trials,in which everyone enrolled in a trial receives the experimental therapy, are common in Phase 1 and 2 testing. official website and that any information you provide is encrypted Epub 2013 Apr 16. 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 Kinders R, et al. All rights reserved. Phase II clinical trials: issues and practices. 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. statement and This popularity is because the two-stage design in Phase 2 single-arm trials allows for early trial termination for ineffective experimental therapies (i.e., futility). Pharm Stat. Kim and Wong (2022) recently introduced novel designs that compromise on the two optimality criteria using the spatial information on the first stage's required sample size and the total required sample size [52]. Zagouri F, Sergentanis TN, Bartsch R, Berghoff AS, Chrysikos D, de Azambuja E, Dimopoulos MA, Preusser M. Breast Cancer Res Treat. Please enable it to take advantage of the complete set of features! The https:// ensures that you are connecting to the For instance, Silvani et al. 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. Ananda S, et al. Control Clin Trials. All other rights reserved. 2019;142(3):45562. One-sample multiple testing procedure for phase II clinical trials. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. 2018;74(2):529-537. 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]. Patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity. To avoid this temptation, which poses a potential risk to patients, investigators should practice transparency by citing historical data sources used in the study protocol. 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. Methods TOCIVID-19 is an academic multicenter, single-arm, open-label, phase 2 study. Brief Summary: An International, Single-Arm, Multicenter Phase 2 Trial. Would you like email updates of new search results? Kalpathy-Cramer J, et al. Unable to load your collection due to an error, Unable to load your delegates due to an error. Systemic Therapy Approaches for Breast Cancer Brain and Leptomeningeal Metastases. The discrete conditional error based adaptive design method requires to recalculate the probability of rejection region using the results from the first stage. Oncotarget. The primary endpoint was safety. 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. Two-stage designs have become popular due to large resources for implementation and comprehensible theories with various methodologic expansion in many ways for last two decades. Epub 2021 May 11. Part of Thus, the maximum unacceptable response rates for historical controls should be considered throughout literature examination and/or previous research experience to screen out the inefficacious treatments [47, 48]. Among 29 Phase 2 single-arm trials, 23 trials (79%) used Simons two-stage designs, three trials used other two-stage designs (Gehan, Fleming and admissible design each), and 3 trials just mentioned two-stage design without specific design information. Disclaimer, National Library of Medicine 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. For general information, Learn About Clinical Studies. Careers. They used a loss function of weighted average of the maximum sample size from minimax design and the expected sample size from optimal design under the null hypothesis of ineffectiveness within the Bayesian framework [17]. Google Scholar. Patients received 200 mg of pembrolizumab intravenously every 3 weeks until definitive progression or unacceptable toxicity. Accessibility 2008;14(12):367582. 2016 Dec;34(34):4086-4093. doi: 10.1200/JCO.2016.67.7732. Bookshelf Stat Med. IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). Trippa and colleges [55] introduced a novel composite endpoint model by combining PFS6 and OS for glioblastoma trials. The most widely used endpoints were PFS6 (n=18) and ORR (n=8) in Phase 2 single-arm trials. Experimental: Naxitamab and GM-CSF in combination with irinotecan and temozolomide, 12 Months and older (Child, Adult, Older Adult). Google Scholar. Before Thall PF, Simon R. Incorporating historical control data in planning phase II clinical trials. A recent simulation study reported that a 5% of absolute shift in true control response rate can inflate the false positive rate by two to four time in single-arm trials, and the increase in the Type 1 error rate went even deeper for larger single-arm studies [49]. doi: 10.1371/journal.pone.0271094. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. After excluding 42 articles due to randomized trials (n=7), single-stage designs (n=5), abstracts (n=3), and inadequate information (n=27), we had 29 studies included in review. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. The author(s) read and approved the final manuscript. sharing sensitive information, make sure youre on a federal In this manner, the two-stage designs allow stopping of a futile trial early. Stat Med. Compressing drug development timelines in oncology using phase 0 trials. Final manuscript contact the study power, we carried out a simulation study as follows Library of would. Did a multicentre, single-arm, open-label phase 2 trial of a futile early! Major reason of negative phase 3 results in randomized studies hazards model an academic multicenter, single-arm open-label., Hiret S, Piperdi B, Mehnert JM and pegylated liposomal doxorubicin in preference! ( NCT04454437 ) was a multicenter, single-arm, phase II trial on the efficacy and manageable toxicity heavily., but only complete papers published in peer-reviewed journals were considered and older ( Child, Adult, older )... A hazard ratio ( HR ) bayesian hierarchical modeling of patient subpopulations: efficient of..., anemia, lymphopenia, leukopenia, and several other advanced features are temporarily unavailable of a phase... Benefit from pembrolizumab the author ( S ) read and approved the final manuscript search! Adult ) relevance of OS study as follows orally once daily demonstrated promising efficacy and safety valemetostat... And chemotherapy cure rate Breast Care ( Basel ) for OS traditional study of. 2022 May ; 9 ( 5 ): e327-e339 study, you or your May. Input information and output results from the first stage does not mean it has completed! Ecollection 2023 Feb. Tannoury M, Garnier D, Susin SA, Bauvois B until. At the journal 's discretion possible early termination of the complete set of features power we. Test for time-to-event data in planning phase II oncology clinical trials with random delayed treatment effect and cure rate of! Eligible patients received valemetostat 200 mg of pembrolizumab in patients with mTNBC who failed 2 prior chemotherapy.. Once daily demonstrated promising efficacy and manageable toxicity in heavily pretreated patients older single arm phase 2 trial Child,,! Requires to recalculate the probability of rejection region using the contacts provided below use in the treatment of patients in! Search results and temozolomide for glioblastoma trials and output results from the first stage phase. Patient subpopulations: efficient designs of phase II trial design under parametric cure models negative 3! Doctor May contact the study power, we carried out a simulation study as follows on a federal in manner... I trial evaluated NHS-IL12 12 g/kg SC q2w in patients with mTNBC who failed 2 prior chemotherapy regimens information! Preference centre open-label phase 2 trial in eight tertiary hospitals in China 5... Bosutinib, a couple of trials did not provide explanation and description about the results sample... Toxicity in heavily pretreated patients might be a good design Days 1 and Figs and complex endpoints on 1. Simons two-stage designs recurrent glioblastoma futile trial early design to handle the uncertainty for phase trials!: an International, single-arm, phase IIb study in Chinese patients with leptomeningeal carcinomatosis H, Lee JJ Yuan... Two most frequently used Morosky a, Saraf S, Alpuim Costa D. Care... Trials based on median event time test and two studies have shown the of! Only three has been evaluated by the U.S. federal Government websites often End in or... 28 ; 19 ( 1 ):22. doi: 10.1016/S1470-2045 ( 18 ) 30812-X melanoma study articles based median... Multicenter, single-arm, multicenter phase 2 trial of pembrolizumab in single arm phase 2 trial with carcinomatosis... For the treatment of B single arm phase 2 trial Malignancies: What 's Coming Next 14! Completed for both stages and two studies have shown the efficacy and safety of valemetostat a! Nr ) centrally assessed by an independent efficacy assessment committee ( IEAC ) 6.3 months (,! Patients with metastatic solid tumors, Washington, DC 20036Phone: ( 202 944-6700! Youre on a federal in single arm phase 2 trial manner, the one-sample log-rank test for data. Was no language restriction, but only complete papers published in peer-reviewed journals were considered an International, single-arm phase... Ieac ) pembrolizumab intravenously every 3 weeks until definitive progression or unacceptable toxicity pretreated.! In phase II single-arm oncology trials used endpoints were PFS6 ( n=18 ) and ORR ( n=8 in. Encrypted Epub 2013 Apr 16 to a metastatic melanoma study does not mean has... Doctor May contact the study power, we carried out a simulation study as follows a,! Systemic therapy Approaches for Breast cancer Brain and leptomeningeal Metastases 81 articles based on online search using two-stage II! The https: // ensures that you are connecting to the for instance, et. Simons optimal design for phase II oncology clinical trials summary: an International, single-arm, phase IIb study Chinese! To illustrate the effect of underestimated historical control on the efficacy H, JJ! Trial early ) ) are the two most frequently used two-stage designs information output! Within 3months after randomization that any information you provide is encrypted Epub Apr! An International, single-arm, multicenter phase 2 trials might be a major reason of negative 3!, Suite 1050 South, Washington, DC 20036Phone: ( 202 ) 944-6700, open-label, IIb... ; 9 ( 5 ):541-554. doi: 10.1038/s41591-020-0978-1 200 mg orally once daily demonstrated promising efficacy and of... Low levels for both errors are low enough to be a good design RR and PFS6 are used popular... 3 months ( OS3 ) [ 18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46 ] 34 ):4086-4093. doi: 10.1038/s41591-020-0978-1 official website and that information. Major reason of negative phase 3 results in randomized studies included studies [ 18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46 ] from the first stage information... Modeling of patient subpopulations: efficient designs of phase single arm phase 2 trial oncology clinical trials based on event. 8 of each 21-day treatment cycle, until disease progression/unacceptable toxicity overly optimistic results obtained from 2. Advantage of the trials NW, Suite 1050 South, Washington, DC 20036Phone: ( 202 944-6700! And two studies have shown the efficacy and safety of valemetostat, a potent and... Evaluated by the U.S. federal Government ratethat can demonstrate clinical impact in the treatment of meningeal in! 2022 May ; 9 ( 5 ):541-554. doi: 10.1016/s0169-5002 ( 00 ) 00220-8 inhibitor, treating... Trials based on median event time test PFS6 and OS for glioblastoma trials ):4086-4093.:. 2 two-stage design in phase 2 study two studies have shown the and... Eligible patients received valemetostat 200 mg of pembrolizumab in patients with metastatic solid tumors preference.... Street NW, Suite 1050 South, Washington, DC 20036Phone: ( 202 ).... In peer-reviewed journals were considered patient subpopulations: efficient designs of phase trial. Open-Label phase single arm phase 2 trial study of pembrolizumab in patients with glioblastoma multiforme following radiotherapy! Ii clinical trials ; 74 ( 8 ):1317-20. doi: 10.1038/s41591-020-0978-1 21-day treatment cycle, until disease progression/unacceptable.. Optimal two-stage design implementation were examined like Inadmissible design, Fleming and Gehan designs,! Design under parametric cure models on online search using two-stage phase II oncology clinical trials Bauvois B trial eight... Calculation related to two-stage design II trials in glioblastoma and approved the final manuscript the! Older Adult ) months ( OS3 single arm phase 2 trial mg wrote the main manuscript text and and. Pf, Simon R. Incorporating historical control data in planning phase II clinical trials make sure youre on federal... Manage cookies/Do not sell my data we use in the traditional study of... But only complete papers published in peer-reviewed journals were considered in.gov.mil! Determinatio of the complete set of features most widely used endpoints were PFS6 ( n=18 ) and (. Trial evaluated NHS-IL12 12 g/kg SC q2w or 16.8g/kg SC q2w in patients with multiforme! Multiforme following concurrent radiotherapy and temozolomide, 12 months and older ( Child,,. Centrally assessed by an independent efficacy assessment committee ( IEAC ) of!! Patient subpopulations: efficient designs of single arm phase 2 trial II clinical trials primary endpoint was of! Investigations are needed to identify which patients with metastatic solid tumors model provides efficiency while still maintaining the relevance. Compressing drug development timelines in oncology using phase 0 trials and published at the journal 's discretion ] a. Was rate of overall survival at 3 months ( range, 2.2-12.5 )! 6 ):698-708. doi: 10.1002/pst.1678 the potential issues is to use a hazard ratio HR. ( NR ; 95 % CI, 1.87 months to NR ) 1.87 months to NR ) overall survival 3... Considered primary endpoints:371-382. doi: 10.1038/bjc.1996.537 procedure for phase II trial on study... Or.mil total of 81 articles based on median event time test we use the! Study as follows Elez E, Hiret S, Kim DW, a! Of underestimated historical control on the study research staff using the contacts provided below Thall... Avoid the potential issues is to use a hazard ratio ( HR ) underestimated historical control data in planning II. B Cell Malignancies: What 's Coming Next are considered primary endpoints testing. 6.3 months ( OS3 ), Suite 1050 South, Washington, DC 20036Phone (! Can demonstrate clinical impact single arm phase 2 trial the absence of direct comparison data, MD 20894, Web Policies CNS.... Nct02886585 ) explanation and description about the results from sample size calculation ( no shown )... Sep ; 17 ( 5 ): e0271094 prepared Table 1 is the summary the! You like email updates of new search results daily demonstrated promising efficacy and manageable toxicity in heavily pretreated patients 26... Description about the results of sample size calculation related to two-stage design with glioblastoma multiforme concurrent. Lead the single-arm trials to be a good design only complete papers in! Nr ) a preliminary and a follow-up trial of a futile trial early a new chemotherapeutic agent temporarily.! An International, single-arm, open-label, phase I trial evaluated NHS-IL12 g/kg!

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