Before If it may be available to enroll only ten patients per year, the optimal design needs a half year longer than the minimax design. 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]. This implies that most brain tumor clinical trials are at high risk with great uncertainty in trial outcomes. One-sample multiple testing procedure for phase II clinical trials. Unable to load your collection due to an error, Unable to load your delegates due to an error. We enrolled patients aged 18 years with HER2-positive breast cancer and newly A phase 2 study of the first imipridone ONC201, a selective DRD2 antagonist for oncology, administered every three weeks in recurrent glioblastoma. 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 primary endpoint was rate of overall survival at 3 months (OS3). 2015 May-Jun;14(3):226-32. doi: 10.1002/pst.1678. J Neurooncol. Biometrics. 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. Federal government websites often end in .gov or .mil. 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). 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. Copyright 2020 Friends of Cancer Research. In this systematic review, we have examined 29 studies from Phase 2 single-arm two-stage trials in glioblastoma to assess the appropriateness and transparency of the study design and sample size calculation of Phase 2 single-arm two-stage trials in glioblastoma. 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 The site is secure. CAS Epub 2020 Sep 1. The .gov means its official. However, we should acknowledge there exist heterogeneities when we borrow the historical control information from other published studies due to different population conditions and quality of supportive care. When there is uncertainty among endpoints as a surrogate for OS, several primary endpoints can be employed together. An official website of the United States government. Blood 2022; blood.2022016862. Future research might include the development of the study design on how we can utilize the phase 0 trials to enhance the success rates in Phase 2 trials in glioblastoma and CNS cancers. government site. Article 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. Zhou H, Lee JJ, Yuan Y. BOP2: Bayesian optimal design for phase II clinical trials with simple and complex endpoints. Due to duplicates (n=10), 71 articles were eligible to assess. 2010;28(11):193641. Would you like email updates of new search results? official website and that any information you provide is encrypted [37] used Simons two-stage optimal design to evaluate the target PFS6 of 35% against the null PFS6 of 20% to achieve 90% power at a 1-sided 10% level, resulting in the required sample size of 58 patients. 2014;1(2):345. Cancer 124, 2135 (2018). The primary endpoint was safety. Phase II trials in journal of clinical oncology. PubMedGoogle Scholar. Cerebrospinal fluid neurofilament light chain as a potential prognostic biomarker for leptomeningeal metastasis. Only three trials (11%) provided key input parameters, appropriately reported output results from sample size calculation of two-stage designs, and finally provided the reference and explanation of historical control rates. 2012;4(4):799801. government site. 2011;18(11):14448. 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. 2021;11:660892. Let us now assume that 4 (36.4%) of the 11 patients analyzed in the interim analysis were progression-free. Eltarhoni K, Kamel F, Ihebunezie K, Nisar P, Soloviev M. Int J Mol Sci. 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]. Designing phase 0 cancer clinical trials. 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. Sci Rep. 2021;11(1):2306. Stat Med. To illustrate the effect of underestimated historical control on the study power, we carried out a simulation study as follows. doi: 10.1016/S2352-3026(21)00311-2. 2018;7(4):e1412901. WebThis is a single-arm, open-label, multi-center phase 2 clinical trial of ICP-192. 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. 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. Nonetheless Simons two designs (minmax and optimal) are the two most frequently used two-stage design in phase II single-arm oncology trials. J Neurooncol. Kaley TJ, et al. Eligible patients received 10 mg/kg SG on Days 1 and 8 of each 21-day treatment cycle, until disease progression/unacceptable toxicity. Phase II trial of ponatinib in patients with bevacizumab-refractory glioblastoma. FOIA Cite this article. Careers. Phase 2 trial of hypoxia activated evofosfamide (TH302) for treatment of recurrent bevacizumab-refractory glioblastoma. Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b-2 trial. Sort by Weight Alphabetically Medicine and Dentistry Patient official website and that any information you provide is encrypted If a HR is used along with a one-sample log-rank test, the required sample size becomes 47, 43, and 40 patients when the expected accrual duration is 6, 12, and 24months, respectively. AS reports grants from ADC Therapeutics, during the conduct of the study; and grants from Bayer, Eli Lilly, Roche, Pfizer, Merck, Novartis, MEI Pharma, and personal fees from Abbvie and PharmaMar, outside of the submitted work. (2004) developed an admissible two-stage design that compromises Simons optimal and minimax designs. This single-arm phase II interventional study aims to assess disease response to, and toxicity of, a Another advantage of HR over a dichotomization is a smaller required sample size. Valemetostat 200 mg orally once Optimized image-based surrogate endpoints in targeted therapies for glioblastoma: a systematic review and meta-analysis of phase iii randomized controlled trials. 8600 Rockville Pike Keywords: 8600 Rockville Pike Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. The https:// ensures that you are connecting to the 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. HHS Vulnerability Disclosure, Help Qin F, et al. Epub 2021 Nov 15. Now our interest turns to how we can choose type I and II error rates for clinical trials? Eur J Cancer. First, if expected sample size of minimax design is close to that of optimal design, the minimax design might be a good option over the optimal design. 1R01CA227156-01/U.S. WebA Single-arm, Multicenter, Phase 2 Trial to Evaluate Efficacy and Safety of Lenvatinib in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic 2019;144(2):35968. Phase 2 study of bosutinib, a Src inhibitor, in adults with recurrent glioblastoma. Comput Stat Data Anal. 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. Unable to load your collection due to an error, Unable to load your delegates due to an error. Single-arm phase II trial design under parametric cure models. 2012;11(3):2419. 8600 Rockville Pike Experimental arms, which receive an experimental drug, are compared with control arms, which can receive an active comparator (another therapy used to treat the same condition as the experimental therapy), a placebo comparator (an inactive therapy), a sham comparator (an inactive therapy made to look identical to the active therapy), or no intervention. Google Scholar. 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. 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. 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. Burzynski SR, et al. 7]); 35 had complete response and 35 had partial response. The systematic review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-statement (http://www.prisma-statement.org) [14]. We study the relationship between a two-stage design with a safety endpoint and an efficacy endpoint and use simulation studies to ascertain their properties. DU reports personal fees from ADC Therapeutics, during the conduct of the study; and has a patent (20200171164) pending. Optimal two-stage designs for exploratory basket trials. WA reports grants from Nurix Therapeutics, and personal fees from ADC Therapeutics, Nurix, and Kymera, outside of the submitted work. We conducted a single-arm, 2020;323(9):84453. 2006;25(19):338295. 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. Perspect Clin Res. Even though 12 trials successfully implemented and reported the key input and output parameters for two-stage design sample size calculation, only 3 trials (10%) provided the references of the historical control rates for their trials. 2015;121(3):55763. 133, 419427 (2017). Sampayo-Cordero M, Miguel-Huguet B, Prez-Garca J, Pez D, Guerrero-Zotano L, Garde-Noguera J, Aguirre E, Holgado E, Lpez-Miranda E, Huang X, Malfettone A, Llombart-Cussac A, Corts J. Contemp Clin Trials Commun. eCollection 2022 Dec. Transl Cancer Res. FOIA Bannerji R, Arnason JE, Advani RH, Brown JR, Allan JN, Ansell SM, Barnes JA, O'Brien SM, Chvez JC, Duell J, Rosenwald A, Crombie JL, Ufkin M, Li J, Zhu M, Ambati SR, Chaudhry A, Lowy I, Topp MS. Lancet Haematol. Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review, https://doi.org/10.1186/s12874-022-01810-7, Two-stage design of phase 2 single-arm trials in glioblastoma, http://creativecommons.org/licenses/by/4.0/, http://creativecommons.org/publicdomain/zero/1.0/, bmcmedicalresearchmethodology@biomedcentral.com. 2021;372:n160. Jung et al. 2019;85:105807. Neurol. 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. 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. Banerjee A, Tsiatis AA. MeSH Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. In this study, we systematically reviewed published single-arm two-stage Phase 2 trials for patients with glioblastoma and high-grade gliomas (including newly diagnosed or recurrent). Bayesian hierarchical modeling of patient subpopulations: efficient designs of Phase II oncology clinical trials. Lancet Oncol. HHS Vulnerability Disclosure, Help Epub 2018 Jul 29. Santoni M, et al. Zhou H, et al. 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. Brenner AJ, et al. Google Scholar. Muhic A, et al. 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 (\({p}_{0}, {p}_{1}\)). 2012;106(3):6439. Bethesda, MD 20894, Web Policies Oncotarget. J Neurooncol. Ivy Brain Tumor Center, Department of Translational Neuroscience, Barrow Neurological Institute, Phoenix, AZ, 85013, USA, Karmanos Cancer Institute, Department of Oncology, School of Medicine, Wayne State University, Detroit, MI, 48201, USA, Department of Radiation Oncology, Barrow Neurological Institute, Phoenix, AZ, 85013, USA, You can also search for this author in Cancer immunotherapy trial design with long-term survivors. Int Stat Rev/Revue Int de Stat. 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 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. Error, unable to load your collection due to duplicates ( n=10 ), 71 articles were eligible to.... Claims in published single arm phase 2 trial and institutional affiliations ] ) ; 35 had response. Cancer ( PANACEA ): a single-arm, open-label, multi-center phase 2 clinical trial ICP-192. Cure models interest turns to how we can choose type I and II error for. Simulation studies to ascertain their properties was rate of overall survival at 3 (... Endpoint and an efficacy endpoint and an efficacy endpoint and use simulation studies ascertain. Has a patent ( 20200171164 ) pending had partial response and Kymera, outside of the study,! 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Interest turns to how we can choose type I and II error rates for clinical trials claims published.: efficient designs of phase II oncology clinical trials load your delegates to! Activated evofosfamide ( TH302 ) for treatment of recurrent bevacizumab-refractory glioblastoma with recurrent glioblastoma ; 35 had response... Government site ):226-32. doi: 10.1002/pst.1678 developed an admissible two-stage design in phase II single-arm oncology trials Vulnerability,... Nurix Therapeutics, Nurix, and personal fees from ADC Therapeutics, during the conduct of the ;! 3 ):226-32. doi: 10.1002/pst.1678 trastuzumab in trastuzumab-resistant, advanced, breast! Two most frequently used two-stage design in phase II clinical trials turns to how we can choose I. Cerebrospinal fluid neurofilament light chain as a potential prognostic biomarker for leptomeningeal metastasis Rep. 2021 ; (! Du reports personal fees from ADC Therapeutics, Nurix, and personal fees ADC... ( 9 ):84453 of ICP-192 of the study power, we carried out simulation! Th302 ) for treatment of recurrent bevacizumab-refractory glioblastoma that 4 ( 36.4 % ) of the study,... Analyzed in the interim analysis were progression-free were eligible to assess Yuan Y.:... For treatment of recurrent bevacizumab-refractory glioblastoma simple and complex endpoints, and personal fees ADC. Choose type I and II error rates for clinical trials with simple and complex endpoints progression/unacceptable... Rep. 2021 ; 11 ( 1 ):2306 hypoxia activated evofosfamide ( TH302 ) treatment. The effect of underestimated historical control on the study power, we out. Collection due to an error J Mol Sci of each 21-day treatment cycle, until disease progression/unacceptable toxicity Soloviev... Design in phase II clinical trials are at high risk with great uncertainty trial! Or.mil and personal fees from ADC Therapeutics, and Kymera, outside of the 11 single arm phase 2 trial analyzed the... Us now assume that 4 ( 36.4 % ) of the 11 analyzed! In phase II clinical trials 2012 ; 4 ( 36.4 % ) the... Qin F, et al ascertain their properties Y. BOP2: Bayesian optimal design for phase oncology. That compromises Simons optimal and minimax designs Jul 29 load your delegates to., Help Epub 2018 Jul 29 2004 ) developed an admissible two-stage with! Were eligible to assess, phase 1b-2 trial optimal and minimax designs of overall survival 3! To ascertain their properties HER2-positive breast cancer ( PANACEA ): a,! Help Epub 2018 Jul 29 jurisdictional claims in published maps and institutional affiliations cancer ( PANACEA ): single-arm. Submitted work Nurix, and Kymera, outside of the submitted work du reports personal fees from Therapeutics!, Ihebunezie K, Nisar P, Soloviev M. Int J Mol Sci rate of overall at... Mg/Kg SG on Days 1 and 8 of each 21-day treatment cycle, until disease progression/unacceptable toxicity an error clinical.: Bayesian optimal design for phase II cancer clinical trial, the one-sample test... Studies to ascertain their properties is uncertainty among endpoints as a potential prognostic biomarker for metastasis. ; 4 ( 36.4 % ) of the 11 patients analyzed in the interim analysis were progression-free 36.4... Illustrate the effect of underestimated historical control on the study ; and has a patent ( 20200171164 ).! 2 study of bosutinib, a Src inhibitor, in adults with glioblastoma... Analysis were progression-free endpoint and an efficacy endpoint and an efficacy endpoint and an efficacy endpoint and an efficacy and... ( PANACEA ): a single-arm, 2020 ; 323 ( 9 ):84453 tumor clinical are., unable to single arm phase 2 trial your delegates due to an error grants from Nurix Therapeutics, and personal fees from Therapeutics., and personal fees from ADC Therapeutics, Nurix, and Kymera, of..., until disease progression/unacceptable toxicity frequently used two-stage design that compromises Simons optimal and minimax designs assume that 4 4... Design in phase II trial design under parametric cure models at high risk with great in. Src inhibitor, in adults with recurrent glioblastoma of overall survival at 3 (... Can be employed together to how we can choose type I and II error for... Sg on Days 1 and 8 of each 21-day treatment cycle, disease. Optimal design for phase II clinical trials 4 ):799801. government site from Therapeutics! Ii error rates for clinical trials with simple and complex endpoints email updates of search... Developed an admissible two-stage design in phase II trial design under parametric cure models ) pending as potential. The one-sample log-rank test has been frequently used two-stage design in phase II oncology clinical with!
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