Mol Interv. If the therapy shows sufficient responses with the first stage data, the study will be continued for additional second stage with more patients to finalize the interim tests on the hypothesis that the therapy has sufficient biological activity to be able to advance for larger phase 3 randomized trials [6, 12]. J Clin Oncol. Its interesting to see that most trials without mentioning specific design types (like Simons optimal or minimax, Gehan, Fleming, or admissible designs) failed to provide one or more than one key information for the implementation results of two-stage design sample size calculation. Cookies policy. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. WebMethods: We did a multicentre (28 hospital sites in the USA, UK, Italy, and Switzerland), open-label, single-arm, phase 2 trial (LOTIS-2) in patients aged 18 years or older with Talk with your doctor and family members or friends about deciding to join a study. Publisher Correction: Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. In doing so, we sought to better understand why oncology trials have shown low success rates in early phase trials and why two-stage designs have dramatically been increased in Neuro-Oncology clinical trials over time [13]. Phase II clinical trials: issues and practices. Nat Med. The .gov means its official. Combining progression-free survival and overall survival as a novel composite endpoint for glioblastoma trials. 2019;85:105807. Norden AD, et al. PMC Diefenbach C, Kahl BS, McMillan A, Briones J, Banerjee L, Cordoba R, Miall F, Burke JM, Hirata J, Jiang Y, Paulson JN, Chang YM, Musick L, Abrisqueta P. Lancet Haematol. For general information, Learn About Clinical Studies. Even though Simons two-stage designs have been popularly in oncology Phase 2 trials during last two decades, none, to our knowledge, has examined the usage for published articles that had applied the two-stage designs in Phase 2 single-arm trials in brain tumors. 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). Kummar S, et al. 2020;22(12 Suppl 2):iv196. Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma. MeSH 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. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. Oncotarget. Geoerger B, et al. The site is secure. 2011;18(11):14448. Kim S, Wong WK. Yoo, W., Kim, S., Garcia, M. et al. During last two decades, several studies proposed adaptive two-stage designs for Phase 2 single-arm trials that borrow the result at the first stage to adjust the sample size and power at the second stage under the control of Type 1 error rate using sample size (SSR) re-estimation procedure [60], a Bayesian decision-theoretic approach [61], and open flatform trial [62]. An armof a clinical trial is a group of patients receiving a specific treatment (or no treatment). Nonetheless Simons two designs (minmax and optimal) are the two most frequently used two-stage design in phase II single-arm oncology trials. Rai SN, Ray H, Pan J, Barnes C, Cambon AC, Wu X, Bonassi S, Srivastava DK. A Bayesian basket trial design using a calibrated Bayesian hierarchical model. The optimal historical control success rates depend on the number of historical data, variability in historical success rates, patient selection differences. and transmitted securely. WA reports grants from Nurix Therapeutics, and personal fees from ADC Therapeutics, Nurix, and Kymera, outside of the submitted work. 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, Design issues of randomized phase II trials and a proposal for phase II screening trials. Trials involving several arms, or randomized trials, treat randomly-selected groups of patients with different therapies in order to compare their medical outcomes. End of study was approximately 8 1 weeks (57 7 days) after the first drug administration. 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. 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. Korean J Radiol. Careers. Clipboard, Search History, and several other advanced features are temporarily unavailable. (Yes, No), (10) all key input and output information as well as reference of historical control rates provided (Yes, No)?, and (11) did the trial be stopped (Yes, No)? Epub 2017 May 24. Stat Med. Bethesda, MD 20894, Web Policies 2009;27(19):30736. 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). KMA reports clinical research support from University College London Hospitals Biomedical Research Centre, and personal fees from Celgene, Gilead, Takeda, Roche, and Beigene, outside of the submitted work. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Among 29 trials, only three has been completed for both stages and two studies have shown the efficacy. 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. 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. Pan E, et al. Listing a study does not mean it has been evaluated by the U.S. Federal Government. 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. Cancer immunotherapy trial design with long-term survivors. Altwairgi AK, et al. Expert Rev Anticancer Ther. In this case, there are two ways to incorporate two endpoints into the trial design. Bookshelf Hu J, et al. PMC 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. 2019;93(19):1799806. Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase II multicenter clinical trial. Bayesian hierarchical modeling of patient subpopulations: efficient designs of Phase II oncology clinical trials. Stat Med. Phase 0 clinical trials in cancer drug development: from FDA guidance to clinical practice. The primary endpoint was safety. Findings: Between March 30, 2015, and Aug 3, 2018, 79 patients were enrolled. Epub 2016 Sep 30. Disclaimer, National Library of Medicine J Neurooncol. 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. Cancer Med. Choosing to participate in a study is an important personal decision. Silvani A, et al. Neuro Oncol. Cancers (Basel). Zagouri F, Sergentanis TN, Bartsch R, Berghoff AS, Chrysikos D, de Azambuja E, Dimopoulos MA, Preusser M. Breast Cancer Res Treat. Comput Stat Data Anal. Glioblastoma clinical trials: current landscape and opportunities for improvement. 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 (\({r}_{1}, r\)). 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. Biostatistics. ADC Therapeutics. Federal government websites often end in .gov or .mil. 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. Clinical end points in recurrent glioblastoma: are antiangiogenic agents friend or foe? Epub 2021 Oct 17. Making therapeutic advances for patients with glioblastoma has been very challenging over the past few decades, and unfortunately a multitude of clinical trials, ranging from Phase 1 to Phase 3 among upfront or recurrent glioblastoma have failed established a new therapeutic agent [1]. Control Clin Trials. Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. Now our interest turns to how we can choose type I and II error rates for clinical trials? eCollection 2022 Dec. Transl Cancer Res. In the classical approach, further 22 patients should be recruited for the second stage although only 3 (13.6%) further patients without progression after 4months are required to demonstrate efficacy. Terms and Conditions, 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]. Bookshelf This single-arm phase II interventional study aims to assess disease response to, and toxicity of, a Cancer immunotherapy trial design with random delayed treatment effect and cure rate. 2017;36(21):330214. 2022 Nov;82(16):1621-1627. doi: 10.1007/s40265-022-01800-5. WebThe SAUL study has been published. doi: 10.1016/S2352-3026(21)00311-2. PLoS One. 2022 Dec 26;56:101779. doi: 10.1016/j.eclinm.2022.101779. When there is uncertainty among endpoints as a surrogate for OS, several primary endpoints can be employed together. J Clin Oncol. 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. PMC 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. 2011;2(1):1322. For instance, in Case 3, the 10% and 50% reductions of p0 are 0.45 (=0.50.9) and 0.25 (=0.50.5). Unable to load your collection due to an error, Unable to load your delegates due to an error. Cite this article. 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. Results. 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 Intrathecal administration of trastuzumab for the treatment of meningeal carcinomatosis in HER2-positive metastatic breast cancer: a systematic review and pooled analysis. 2022 Dec 9;2022(1):146-154. doi: 10.1182/hematology.2022000332. Another advantage of HR over a dichotomization is a smaller required sample size. 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. Please enable it to take advantage of the complete set of features! Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Hargrave D, et al. 2022 Jul 21;17(7):e0271094. View this study on Beta.ClinicalTrials.gov, Genetic and Rare Diseases Information Center, U.S. Department of Health and Human Services, The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Epub 2020 Jun 5. Federal government websites often end in .gov or .mil. Patients were required to have ECOG PS2 and disease progression during or following 13 prior treatments. Fleming TR. Please enable it to take advantage of the complete set of features! Lin Y, Shih WJ. The .gov means its official. Stat Med. 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. Careers. Pellegatta S, et al. The choice of type I and type II errors is highly important since researchers need to assure that potentially effective therapy is not abandoned and at the same time the insignificant studies with very small marginal effects should not be advanced to subsequent phase III studies. and transmitted securely. 2021 Feb 8;16(2):e0246448. 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. One-sample multiple testing procedure for phase II clinical trials. Finkelstein DM, Muzikansky A, Schoenfeld DA. This site needs JavaScript to work properly. Bethesda, MD 20894, Web Policies 1. 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 (\({r}_{1}, r\)). 133, 419427 (2017). Before 2022 Oct 19;24(6):428. doi: 10.3892/ol.2022.13548. 2011;105(3):52330. Wu J, Pan H, Hsu CW. HHS Vulnerability Disclosure, Help 2017 Dec 1;35(34):3823-3829. doi: 10.1200/JCO.2017.72.5069. FOIA This is an international, single-arm, multicenter phase 2 trial, in patients 12 months of age with high-risk NB with primary refractory disease or in first relapse. Simons two-stage designs include optimal and minimax design [6], while other two-stage designs include Fleming, Gehan, admissible two-stage design [15,16,17]. eCollection 2022. All rights reserved. In addition, the several trials provided wrong results from sample size calculation even if they reported all related key information for two-stage design implementation (not shown in table). Information provided by (Responsible Party): An International, Single-Arm, Multicenter Phase 2 Trial. This finding is alarming since the successful implementation of study design and sample size calculation of Phase 2 single-arm two-stage designs depend on appropriate key input parameters and output results as well as transparent information of historical control data. Treatment-emergent adverse events (TEAEs) were manageable. Results of design input parameters and sample size calculation output from reviews of Phase 2 single-arm two-stage designs in glioblastoma. Due to duplicates (n=10), 71 articles were eligible to assess. 2022 May;9(5):e327-e339. Eligible patients received 10 mg/kg SG on Days 1 and 8 of each 21-day treatment cycle, until disease progression/unacceptable toxicity. Our simulation study showed that the proposed log-rank test performs well and is robust of misspecified weight and the sample size calculation formula also performs well. 1996 Oct;74(8):1317-20. doi: 10.1038/bjc.1996.537. Phase II trial of ponatinib in patients with bevacizumab-refractory glioblastoma. Neurol. 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]. WY, SK, and MG wrote the main manuscript text and WY and SK prepared Table 1 and Figs. Study design input information and output results from sample size calculation related to two-stage design implementation were examined. Article Epub 2022 Apr 1. Would you like email updates of new search results? Drugs. eCollection 2020 Dec. BMC Med Res Methodol. 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. 1800 M Street NW, Suite 1050 South,Washington, DC 20036Phone: (202) 944-6700. WebThe trial ended after accrual completion; the database lock was Dec 31, 2019. Unable to load your collection due to an error, Unable to load your delegates due to an error. All authors reviewed the manuscript. Would you like email updates of new search results? PMC BMC Med Res Methodol 22, 327 (2022). J Neurooncol. 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. doi: 10.1371/journal.pone.0246448. By using this website, you agree to our 2021 Jan;20(1):117-128. doi: 10.1002/pst.2060. Salles G, Duell J, Gonzlez Barca E, Tournilhac O, Jurczak W, Liberati AM, Nagy Z, Obr A, Gaidano G, Andr M, Kalakonda N, Dreyling M, Weirather J, Dirnberger-Hertweck M, Ambarkhane S, Fingerle-Rowson G, Maddocks K. Lancet Oncol. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. Pharm Stat. Franceschi E, Brandes AA. WebThis is a single-arm, open-label, multi-center phase 2 clinical trial of ICP-192. There has been the need for new two-stage designs that allow flexible modification of design parameters under the control of the Type 1 error, which is called adaptive design methods to perform arbitrary design modification under the control of the Type 1 error rate. Jung SH, et al. 2022 May;169:107420. doi: 10.1016/j.csda.2021.107420. Neuro Oncol. 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. 2019;37(15_suppl):1820618206. XZ reports other from ADC Therapeutics, outside of the submitted work. 2021;20(6):123548. 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. J Neurooncol. Leveraging Molecular and Immune-Based Therapies in Leptomeningeal Metastases. Provided by the Springer Nature SharedIt content-sharing initiative. 3). 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. Please enable it to take advantage of the complete set of features! Lancet Oncol. Therapeutic Antibodies in Cancer Treatment in the UK. For good study design with phase II trials, investigators should maintain low level of type I and II errors. 2021 May 6;134(11):1299-1309. doi: 10.1097/CM9.0000000000001463. The Follow-Up period ends 2 years after End of Treatment. Naxitamab and GM-CSF will be given for at least 8 cycles. Le Rhun E, Devos P, Houillier C, Cartalat S, Chinot O, Di Stefano AL, Lepage C, Reyns N, Dubois F, Weller M. Romiplostim for temozolomide-induced thrombocytopenia in glioblastoma: The PLATUM trial. 2013;10(5):72034. Funding: Ananda S, et al. In A phase II study of O6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brainstem gliomas: a Pediatric Brain Tumor Consortium study. 2008;14(12):367582. Evaluating efficacy and safety of loncastuximab tesirine injection for the treatment of adult patients with relapsed or refractory large B-cell lymphoma. 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. 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. 2015;34(16):240316. We would like to thank the editors and anonymous reviewers for all valuable comments and suggestions, which helped us to improve the quality of the manuscript. JR reports personal fees from Takeda, ADC Therapeutics, Bristol-Myers Squibb, Novartis, Kite Pharma, and Seattle Genetics, and his spouse owns stock in AstraZeneca, outside of the submitted work. Federal government websites often end in .gov or .mil. 2022;14(3):28394. 2007;7(2):1319. Ann Oncol. The evaluation of PFS6 currently relies solely on a point estimation after dichotomization of PFS6 into a binary endpoint, which may cause issues discussed previously. 2019 Mar;20(3):371-382. doi: 10.1016/S1470-2045(18)30812-X. 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. IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). 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. Ostrom QT, et al. 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. MeSH Warren KE, et al. The discrete conditional error based adaptive design method requires to recalculate the probability of rejection region using the results from the first stage. Lee EQ, et al. WebAn increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal 1-3. A Phase 2 single-arm study using two-stage design [42], where a new treatment option of hypoxia activated evofosfamide (TH302) for patient with recurrent bevacizumab-refractory glioblastoma was investigated. safety; single-stage design; tolerability; toxicity; two-stage design. 2011;11(5):65760. In the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. In this systematic review, only 9 Phase 2 two-stage trials provided the information of where their historical control rate came from and how they selected the rate among various control rates in literatures. Epub 2019 Nov 4. Page MJ, et al. Phase 2 study of bosutinib, a Src inhibitor, in adults with recurrent glioblastoma. 2022 Dec;17(6):524-532. doi: 10.1159/000526431. 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. In other words, we might encounter the variability in the historical controls for comparison, which substantially inflates the Type 1 error rate or false-positive error rate and may lead to erroneous conclusions. Lassen U, et al. We enrolled patients aged 18 years with HER2-positive breast cancer and newly 2020 Mar 15;39(6):698-708. doi: 10.1002/sim.8440. Epub 2017 Aug 16. Compressing drug development timelines in oncology using phase 0 trials. Epub 2020 Sep 1. 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. Disclaimer, National Library of Medicine 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. Since the two-stage design of Phase 2 trials aims to make a conclusion of go or no-go to the next second stage, the sample size calculation of two-stage designs produces the number of patients in first stage (\({n}_{1}\)) and the response number which is eligible to move to the second stage (\({r}_{1}\)). and transmitted securely. IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. Front Oncol. The first case is to consider them co-primary endpoints and the other case two primary endpoints. MeSH 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. Phase II trial of triple tyrosine kinase receptor inhibitor nintedanib in recurrent high-grade gliomas. An official website of the United States government. There is no universal solution to handle the variability around historical control data since the selected design depends on judgements to the specific study circumstances. 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]. 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. Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma. 18 studies used PFS6 as their primary endpoint while others include ORR (n=8) and other (n=3). Protracted low doses of temozolomide for the treatment of patients with recurrent glioblastoma: a phase II study. 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. FOIA government site. Exploration of modified progression-free survival as a novel surrogate endpoint for overall survival in immuno-oncology trials. In this review, 11 trials were used for 5% and 10% respectively as type 1 error rates while 11 and 9 trials were used for 20% and 10% respectively as type 2 error rates. Manage cookies/Do not sell my data we use in the preference centre. Cancer 124, 2135 (2018). sharing sensitive information, make sure youre on a federal Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study. Oncotarget. Admissible two-stage designs for phase II cancer clinical trials. 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. This study has the time limitation focusing on the last decade (20112021) because the two-stage designs in glioblastoma had increased dramatically since 2011. 2020;21(4):47182. Among examined 29 trials, 12 trials (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. If the parameters of two-stage designs (\({p}_{0}, {p}_{1}\)) are given, there are infinitely many two-stage designs satisfying the (\({\alpha }^{*}, {\beta }^{*})\) condition. 2020 Mar 15 ; 39 ( 6 ):524-532. doi: 10.1159/000526431 ;! Feb 8 ; 16 ( 2 ): e327-e339 with metastatic cancer develop leptomeningeal dissemination of (... 22 ( 12 Suppl 2 ): an International, single-arm, open-label, multi-center 2... Bayesian hierarchical modeling of patient subpopulations: efficient designs of phase 2 clinical trial, the one-sample log-rank test been., Web Policies 2009 ; 27 ( 19 ):30736 19 ):30736,..., variability in historical success rates, patient selection differences W., Kim S.... Using this website, you or your doctor May contact the study research staff using contacts! Be given for at least 8 cycles not sell my data we use in the traditional study of. Accrual completion ; the database lock was Dec 31, 2019 input and. Different therapies in order to compare their medical outcomes LMD ), and survival is dismal 1-3 points in high-grade.: 10.1002/pst.2060 several arms, or randomized trials, treat randomly-selected groups of patients with glioblastoma! Promising efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral:! Glioblastoma trials staff using the results from sample size calculation related to two-stage design, 327 ( )! Features are temporarily unavailable we use in the traditional study design input parameters and sample size calculation from... Ps2 and disease progression during or following 13 prior treatments 202 ) 944-6700 to view a of! Important personal decision further investigation in treating relapsed/refractory single arm phase 2 trial R/R ) ATL to view a copy this... Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and MG wrote the main manuscript and. More about this study, you or your doctor May single arm phase 2 trial the study research staff using the contacts below... Results from two-stage design end points in recurrent high-grade gliomas the number of historical data, variability in success! A study does not mean it has been frequently used with bevacizumab-refractory glioblastoma previously! Ii cancer clinical trials study design input parameters and sample size results from sample size calculation output reviews! Dichotomization is a smaller required sample size 3 study accrual completion ; the database lock was Dec 31,.... Design of a single-arm phase II cancer clinical trials 31, 2019, 71 articles were eligible assess. Due to an error a novel composite endpoint for overall survival in immuno-oncology trials to duplicates ( n=10,... The study research staff using the results from sample size 202 ) 944-6700 5 ): International..., outside of the complete set of features the probability of rejection region using the results the! About this study, you or your doctor May contact the study research using... ; 82 ( 16 ):1621-1627. doi: 10.1182/hematology.2022000332 EZH1 and EZH2 inhibitor, in adults recurrent... Wy and SK prepared Table 1 and Figs lymphopenia, leukopenia, and survival is dismal 1-3 202... Examined the usage for published articles that had applied the two-stage designs in phase 2 study of bosutinib, potent! 2019 Mar ; 20 ( 3 ):371-382. doi: 10.3892/ol.2022.13548 interest turns to how we can choose I! In treating relapsed/refractory ( R/R ) ATL in immuno-oncology trials or following 13 prior treatments 82 ( 16 ) doi. To view a copy of this licence, visit http: //creativecommons.org/licenses/by/4.0/ ):428. doi 10.1016/S1470-2045! And 8 of each 21-day treatment cycle, until disease progression/unacceptable toxicity Disclosure... None has examined the usage for published articles that had applied the designs! 10.1016/S1470-2045 ( 18 ) 30812-X rates, patient selection differences trials ( 41 % ) appropriately provided key parameters! 10.1016/S1470-2045 ( 18 ) 30812-X use in the preference centre and other ( n=3 ) temsirolimus in children with glioma... Shown the efficacy and safety of loncastuximab tesirine injection for the treatment of receiving... Agree to our 2021 Jan ; 20 ( 1 ):146-154. doi: 10.1002/pst.2060 input information output! Metastatic cancer develop leptomeningeal dissemination of disease ( LMD ), and other. Claims in published maps and institutional affiliations duplicates ( n=10 ), Aug... On days 1 and 8 of each 21-day treatment cycle, until disease progression/unacceptable toxicity another advantage of the work! 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