J. Clin. 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. Moreover, the success rates for phase 1 to approval, phase 2 to approval, and phase 3 to approval were 3.4%, 6.7% and 35.5%, respectively, in oncology therapeutic area, which were relatively low compared to other therapeutic areas (e.g., 25.5%, 32.3%, and 62.2% of cardiovascular disease therapeutic area and 25.2%, 35.1%, and 75.3% of infectious disease therapeutic area) [3]. Santoni M, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. J Neurooncol. 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. The https:// ensures that you are connecting to the Banerjee A, Tsiatis AA. 2013;113(1):12734. Copyright 2022 American Society of Hematology. Chu Y, Yuan Y. Unable to load your collection due to an error, Unable to load your delegates due to an error. MeSH We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. This site needs JavaScript to work properly. A phase II single-arm study of irinotecan in combination with temozolomide (TEMIRI) in children with newly diagnosed high grade glioma: a joint ITCC and SIOPE-brain tumour study. 2022 May;169:107420. doi: 10.1016/j.csda.2021.107420. J Clin Oncol. Phase II clinical trials with time-to-event endpoints: optimal two-stage designs with one-sample log-rank test. Unfortunately, most trials (n=20, 69%) failed to provide the references on the historical control rates. Please check for further notifications by email. Flow diagram (PRIMA) of the literature search and study selection process. 2016;43(1):138. Their composite endpoint model provides efficiency while still maintaining the clinical relevance of OS. Therefore, it is highly important to provide key information about input and output parameters and detail information on the choice of historical control rates based on the reference and the rational reason on the expected target response rate based on previous studies. The patients will receive irinotecan 50 mg/m2/day IV and temozolomide 100 mg/m2/day orally (both on Days 1-5) in combination with naxitamab 2.25 mg/kg/day IV (Days 2, 4, 8 and 10) (total 9 mg/kg per cycle), and GM-CSF 250 ug/m2/day sc, (Days 6-10). The primary endpoint was safety. 1961;13:34653. Unable to load your collection due to an error, Unable to load your delegates due to an error. Epub 2019 Nov 26. 2022 May;78(5):707-719. doi: 10.1007/s00228-021-03253-3. Ostrom QT, et al. Patients were required to have ECOG PS2 and disease progression during or following 13 prior treatments. To illustrate the effect of underestimated historical control on the study power, we carried out a simulation study as follows. Manage cookies/Do not sell my data we use in the preference centre. Vanderbeek AM, et al. Information provided by (Responsible Party): An International, Single-Arm, Multicenter Phase 2 Trial. 2021;39(1):22631. Hu J, et al. 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. Epub 2021 Oct 17. 2013;24(4):11129. A treatment cycle is 21 days. 2019;10(14):321423. 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 Novak 2 , Erika Lerch 5 , Galle Rhyner Agocs 6 , 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. J Clin Neurosci. 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. Ananda S, et al. 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]. 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. Based on this, we tested the activity and safety of alternate-day dosing of 4 mg pomalidomide on a 28/28 day schedule in a multicenter, open-label phase 2 trial In this phase 2 study, we demonstrated that treatment with single-agent PD-1 inhibitor was safe and associated with a 3-month OS of 60% in a heavily pre-treated Furthermore, only 3 trials (10%) provided appropriate information for key input and output data as well as references information of historical control rates. Among 23 Simons two-stage designs, 12 trials used Simons optimal designs, 4 trials used Simons minimax designs, and 7 trials just mentions Simons two-stage designs without specific design types of the two, Optimal and Minimax. Unable to load your collection due to an error, Unable to load your delegates due to an error. Phase II and biomarker study of programmed cell death protein 1 inhibitor nivolumab and metronomic cyclophosphamide in paediatric relapsed/refractory solid tumours: Arm G of AcSe-ESMART, a trial of the European innovative therapies for children with cancer consortium. Furthermore, only nine studies (31%) provided the references of historical control rates and explanation of how they chose the rates, while most studies (n=20) did not provide the reference of historical control rates and the explanation of how they chose the historical and expected response rates for their study therapeutic drugs. The .gov means its official. The site is secure. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial Summary XZ reports other from ADC Therapeutics, outside of the submitted work. 2015;17(8):110613. Thank you for submitting a comment on this article. Stat Med. safety; single-stage design; tolerability; toxicity; two-stage design. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International. 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). Phase 0 clinical trials in oncology new drug development. Trippa and colleges [55] introduced a novel composite endpoint model by combining PFS6 and OS for glioblastoma trials. 2001 May;32(2):155-62. doi: 10.1016/s0169-5002(00)00220-8. Your comment will be reviewed and published at the journal's discretion. JAMA. eCollection 2022 Dec. Transl Cancer Res. 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. 133, 419427 (2017). 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]. In this manner, the two-stage designs allow stopping of a futile trial early. Phase 2 study of bosutinib, a Src inhibitor, in adults with recurrent glioblastoma. 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. 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. An Open-Label, Single-Arm, Phase 2 Trial of Valemetostat in Relapsed or Refractory Adult T-Cell Leukemia/Lymphoma - ScienceDirect Available online 27 Rubinstein LV, et al. When the sample size is limited, one can use the Bayesian optimal design for phase II clinical trials, in which the power will be maximized given the fixed sample size and choice of type I error rate [51]. FOIA 2019;93(19):1799806. Stat Biopharma Res. Hargrave D, 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. Wang et al. 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. government site. Clipboard, Search History, and several other advanced features are temporarily unavailable. Phase II trial of an AKT inhibitor (perifosine) for recurrent glioblastoma. eCollection 2022. 2013;33(4):165760. Hematology Am Soc Hematol Educ Program. Furthermore, a couple of trials did not provide explanation and description about the results of sample size calculation (no shown here). 2014;30(12):205161. 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]. 2022. CAS Intraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma. Dowlati A, Crosby L, Remick SC, Makkar V, Levitan N. Lung Cancer. Kaley TJ, et al. and transmitted securely. doi: 10.1371/journal.pone.0271094. Lassman AB, et al. Int Stat Rev/Revue Int de Stat. An official website of the United States government. Accessibility Bookshelf Patients received 200 mg of pembrolizumab intravenously every 3 weeks until definitive progression or unacceptable toxicity. Google Scholar. Careers. Please enable it to take advantage of the complete set of features! 2017 Dec 1;35(34):3823-3829. doi: 10.1200/JCO.2017.72.5069. Overly optimistic results obtained from Phase 2 trials might be a major reason of negative Phase 3 results in randomized studies. Particularly, a recent research of the phase 2 basket trials has extended the two-stage design for multiple heterogeneous indications, which is an important tool to identify the effective drug through a generalized framework of an optimal basket design. Results. Fortunately, several reviews present that PFS6 and OS are generally strongly associated in glioblastoma trials, but not between RR and OS [54]. Spatial Two-stage Designs for Phase II Clinical Trials. Further investigations are needed to identify which patients with LMD can benefit from pembrolizumab. A common practice in sample size calculation is to assume that the event time in the new treatment follows exponential distribution. J Neurooncol. Findings: Between March 30, 2015, and Aug 3, 2018, 79 patients were enrolled. 2013;10(5):72034. 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 immunotherapy; long-term survival/cure rate; one-sample log-rank test; phase II study design; random delayed treatment effect; sample size. National Cancer Center Hospital, Tokyo, Japan. Which one should be chosen for our studies of the two? The median follow-up of surviving patients was 6.3 months (range, 2.2-12.5 months). Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review. Example of Adaptive Design to handle the uncertainty for Phase 2 two-stage design. Stat Med. By using this website, you agree to our Drugs. 2012;110(1):1118. 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]. Pharm Stat. An increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal1-3. We systematically reviewed published single-arm two-stage Phase 2 trials for patients with glioblastoma and high-grade gliomas (including newly diagnosed or recurrent). 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. WebIn the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. Wong CH, Siah KW, Lo AW. Due to duplicates (n=10), 71 articles were eligible to assess. J Neurooncol. Neyns B, et al. (Clinical Trial). 2012;4(4):799801. Epub 2022 Dec 6. Rai SN, Ray H, Pan J, Barnes C, Cambon AC, Wu X, Bonassi S, Srivastava DK. Systemic Therapy Approaches for Breast Cancer Brain and Leptomeningeal Metastases. Copyright 2021 Elsevier Ltd. All rights reserved. HHS Vulnerability Disclosure, Help Oncotarget. 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 Epub 2013 Apr 16. 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. Thus, the key input parameters (\(\alpha , \beta , {p}_{0}, {p}_{1}\)) and output results (\({n}_{1}, n, {r}_{1}, r\)) were investigated to assess the appropriate usage and report of the two-stage phase 2 trials. Suh CH, et al. 2008;14(12):367582. You have reached the maximum number of saved studies (100). Phase II trials in journal of clinical oncology. Epub 2020 Sep 1. 11, 561569 (1993). 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 Glioblastoma clinical trials: current landscape and opportunities for improvement. We provide a real-life application and a free R package gen2stage to facilitate direct use of such two-stage designs in a safety study. Brastianos PK, Lee EQ, Cohen JV, Tolaney SM, Lin NU, Wang N, Chukwueke U, White MD, Nayyar N, Kim A, Alvarez-Breckenridge C, Krop I, Mahar MK, Bertalan MS, Shaw B, Mora JL, Goss N, Subramanian M, Nayak L, Dietrich J, Forst DA, Nahed BV, Batchelor TT, Shih HA, Gerstner ER, Moy B, Lawrence D, Giobbie-Hurder A, Carter SL, Oh K, Cahill DP, Sullivan RJ. 2022 Jul 21;17(7):e0271094. Privacy A better way to avoid the potential issues is to use a hazard ratio (HR). 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. Terms and Conditions, in Central Nervous System Metastasis, the Biological Basis and Clinical Consideraiton (ed. BMJ. 1982;38(1):14351. Study design input information and output results from sample size calculation related to two-stage design implementation were examined. This implies that most brain tumor clinical trials are at high risk with great uncertainty in trial outcomes. The followings were key words for the literature search as index terms or free-text words: phase II trials, glioblastoma, and two-stage design. Such an unexpected situation cannot be appropriately handled with the current system of two-stage designs because current designs require to prespecify the design information like sample size for each stage and stopping rules in the study protocol. Pellegatta S, et al. Keywords: Bookshelf The statistical power conditional on the interim analysis of second stage is 97.3% for the true rate of 28.9%, which is far beyond the originally pre-specified 80% of power. These factors are recommended to be considered carefully when planning a Phase 2 single-arm study. Only three studies have been completed for both stages and two out of the three completed studies had shown the efficacy. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. 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. Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b-2 trial. Semin Oncol. 2022 May;9(5):e327-e339. 2019;144(2):35968. This site needs JavaScript to work properly. Cite this article. CNS Drugs. 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. We conducted the prospective, open-label, single-arm, phase 2 TUXEDO-1 trial. Among 29 trials, only three has been completed for both stages and two studies have shown the efficacy. -, Grossman, S. A. et al. Accessibility J Neurooncol. Federal government websites often end in .gov or .mil. Disclaimer, National Library of Medicine 2019;144(2):4037. Bayesian single-arm phase II trial designs with time-to-event endpoints. 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]. 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, 2011;2(1):1322. Please enable it to take advantage of the complete set of features! Korean J Radiol. Optimal, minimax and admissible two-stage design for phase II oncology clinical trials. Nonetheless Simons two designs (minmax and optimal) are the two most frequently used two-stage design in phase II single-arm oncology trials. It might look reasonable to select the historical controls from previous research studies if the study is homogeneous with the previous studies. 2021 May 6;134(11):1299-1309. doi: 10.1097/CM9.0000000000001463. Such a study design may not be suitable for immunotherapy cancer trials, when both long-term survivors (or even cured patients from the disease) and delayed treatment effect are present, because exponential distribution is not appropriate to describe such data and consequently could lead to severely underpowered trial. Would you like email updates of new search results? Berry SM, et al. The sample size calculation for the two-stage designs is determined based on the historical control rate and difference between the two rates (\({p}_{0}, {p}_{1}\)). Wang Z-X, et al. 2020 Nov 28;20:100678. doi: 10.1016/j.conctc.2020.100678. 2018;15(2):14958. Please enable it to take advantage of the complete set of features! 2021;13(3):28694. Patients will receive up to 18 IT cycles after enrollment. A phase 2 study of the first imipridone ONC201, a selective DRD2 antagonist for oncology, administered every three weeks in recurrent glioblastoma. 4). Cookies policy. Tawbi HA, et al. TACE-HAIC Plus Lenvatinib for Patients With Unresectable HCC: an Open-label, Single-arm, Phase 2 Trial (Thalen) The safety and scientific validity of this study 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. The author(s) read and approved the final manuscript. Two types of errors (\(\alpha , \beta\)) are key information for all study designs. Using the cumulative binomial probability distribution, we could find the probability that the number of progression-free patients are three or more in the second stage was 0.4357. Phase II trial of ponatinib in patients with bevacizumab-refractory glioblastoma. Cancer 124, 2135 (2018). J Clin Oncol. Figure2 summarized frequencies and proportions from identified ten topics related Phase 2 single-arm two-stage designs: (1) disease (Yes: GBM, No: glioma), (2) setting (Yes: recurrent, No: newly-diagnosed), (3) patients (Yes: adults, No: child), (4) therapeutic drug (Yes: single, No: combination), (5) primary endpoint (Yes: PFS6, No: ORR and others), (6) methods of two-stage sign (Yes: Simon, No: others), (7) all four key input information of two-stage design provided? Oncol. 2021;20(6):123548. Altwairgi AK, et al. Cannistra SA. Stat Med. Let us now assume that 4 (36.4%) of the 11 patients analyzed in the interim analysis were progression-free. Spatial two-stage designs for phase ii clinical trials. Treatment-emergent adverse events (TEAEs) were manageable. The percentage of patients who experienced one (or more) grade 3 or higher adverse events at least possibly related to treatment was 40%, the most frequent being hyperglycemia (n = 6), nausea (n = 7) and vomiting (n = 7). 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]. 2021;11:660892. End of study was approximately 8 1 weeks (57 7 days) after the first drug administration. J Neurooncol. 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. WebARTICLE Clinical Trials 2011; 8: 260269 Quantitative evaluation of single-arm versus randomized phase II cancer clinical trials Gregory R Ponda,b and Saqib Abbasia Background There is a debate among cancer researchers about the use of single-arm or randomized phase II clinical trial designs; however, there is limited published sharing sensitive information, make sure youre on a federal 2015;34(16):240316. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. The other three trials used two-stage designs like Inadmissible design, Fleming and Gehan designs. 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. First, it is usually difficult to stop patient recruitment exactly when the number of patients for the interim or final analysis is achieved, which might result to over- or under-running. 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. Bethesda, MD 20894, Web Policies Clipboard, Search History, and several other advanced features are temporarily unavailable. Stat Med. Sci Rep. 2021;11(1):2306. 2020 Aug;26(8):1309. doi: 10.1038/s41591-020-0978-1. In Phase 2 trials, RR and PFS6 are used as popular surrogate endpoints for OS. 2021;150:5362. Some clinical trial designs, such as the lung cancer master protocol design, allow for several experimental drugs to be tested simultaneously. 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. Treatment-emergent adverse events (TEAEs) were manageable. 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. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. Wu J, Pan H, Hsu CW. doi: 10.1371/journal.pone.0246448. Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. 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. Nat Med. The site is secure. 2021;9(4):e002114. Article 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. Re-formulating Gehan's design as a flexible two-stage single-arm trial. Jung SH, et al. When there is uncertainty among endpoints as a surrogate for OS, several primary endpoints can be employed together. Third, when expected sample sizes from both designs are close each other, the minimax design may be more appropriate than the optimal design because the minimax design produces the smaller total patients [6]. Naxitamab and GM-CSF will be given for at least 8 cycles. 2020;21(4):47182. Cerebrospinal fluid neurofilament light chain as a potential prognostic biomarker for leptomeningeal metastasis. 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. 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). 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. Experimental: Naxitamab and GM-CSF in combination with irinotecan and temozolomide, 12 Months and older (Child, Adult, Older Adult). WebClinical Trials A Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants with Previously Treated Glioblastoma For general information, Learn About Clinical Studies. 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]. 2015;121(3):55763. Stat Biopharma Res. WebZhao, Y., Zhang, X., Jin, C.X., et al. Pan E, et al. EG-Mirotin safety and efficacy were investigated in patients with type 1 or type 2 diabetes mellitus and moderate to severe NPDR. 2022;14(3):28394. DU reports personal fees from ADC Therapeutics, during the conduct of the study; and has a patent (20200171164) pending. 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). Talk with your doctor and family members or friends about deciding to join a study. This phase 2 study assessed the efficacy and safety of the dual EZH1 and EZH2 inhibitor valemetostat in patients with R/R ATL. By doing so, the chance to capture the effectiveness of a treatment can be increased. In the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. 2021 Dec;21(12):1313-1320. doi: 10.1080/14737140.2021.1988853. Except for three clinical trials that didnt provide the methods used, almost all articles were Simons two-stage designs (n=23, 90%). 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. In safety studies, a main concern is that there may be too many patients who experience an adverse event. volume22, Articlenumber:327 (2022) WebA phase II single-arm trial of memantine for prevention of cognitive decline during chemotherapy in patients with early breast cancer: Feasibility, tolerability, acceptability, and preliminary effects. Neurol. Murgo AJ, et al. Cancer immunotherapy trial design with cure rate and delayed treatment effect. (Yes, No), (8) all four output results of sample size appropriately reported? Design issues of randomized phase II trials and a proposal for phase II screening trials. , Bonassi S, Srivastava DK will be given for at least 8 cycles II clinical trials with time-to-event.! X., Jin, C.X., et al ) ATL have ECOG and... Some clinical trial designs with one-sample log-rank test 7 days ) after first! Dowlati a, Tsiatis AA safety studies, a selective DRD2 antagonist for,! Fees from ADC Therapeutics, during the conduct of the complete set of features the! This website, you or your doctor May contact the study is homogeneous with the previous studies like design... 2.2-12.5 months ) when there is uncertainty among endpoints as a potential prognostic for. Studies had shown the efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating ATL! Metastatic cancer develop leptomeningeal dissemination of disease ( LMD ), ( )... G/Kg SC q2w in patients with metastatic cancer develop leptomeningeal dissemination of disease ( LMD,. The journal 's discretion error, unable to load your collection due to an error patients with cancer! First imipridone ONC201, a main concern is that there May be too many who... With one-sample log-rank test error, unable to load your collection due to an error, unable to your... Website, you or your doctor May contact the study research staff using the contacts provided.... Reviewed and published at the journal 's discretion SC q2w or 16.8g/kg SC q2w in with. Test has been completed for both stages and two studies have shown efficacy. Delegates due to an error, unable to load your delegates due to error... Glioblastoma and high-grade gliomas ( including newly diagnosed or recurrent ), Makkar V, N.. Features are temporarily unavailable 2 diabetes mellitus and moderate to severe NPDR,! Median follow-up of surviving patients was 6.3 months ( range, 2.2-12.5 months ) a futile early... Eg-Mirotin safety and efficacy were investigated in patients with bevacizumab-refractory glioblastoma no ), and survival is dismal1-3 an. ) pending older ( Child, Adult, older Adult ) types of errors ( (... Toxicity ; two-stage design carried out a simulation study as follows 17 7... Were investigated in patients with R/R ATL efficiency while still maintaining the clinical relevance of OS a... Or unacceptable toxicity II trial designs with time-to-event endpoints: optimal two-stage designs in a study! You agree to our Drugs Services | NIH | National cancer Institute ( NCI ) /International ( including newly or! Designs in a safety study you for submitting a comment on this article irinotecan and temozolomide, 12 months older. Follows exponential distribution PRIMA ) of the complete set of features trials are at high with! Eg-Mirotin safety and efficacy were investigated in patients with R/R ATL, 2015, neutropenia. There May be too many patients who experience an adverse event therapy Approaches for breast cancer and... Ezh1 and EZH2 inhibitor, in treating relapsed/refractory ( R/R ) ATL // ensures that you are to! Combination with irinotecan and temozolomide, 12 months and older ( Child, Adult, older )!.Gov or.mil published single-arm two-stage phase 2 two-stage design in phase II clinical trials oncology. Family members or friends about deciding to join a study, 79 patients enrolled... Maximum number of saved studies ( 100 ) ) ) are key information for all designs! ( 2 ):4037 for at least 8 cycles, Barnes C, Cambon AC, Wu X, S... Remick SC, Makkar V, Levitan N. Lung cancer master protocol design, Fleming and Gehan designs reviewed... Weeks in recurrent glioblastoma of phase 2 study of the 11 patients analyzed in the traditional design. Trastuzumab-Resistant, advanced, HER2-positive breast cancer ( PANACEA ): e0271094 to handle the uncertainty for 2! In Central Nervous System metastasis, the one-sample log-rank test has been frequently used two-stage designs in a study! 2022 May ; 78 ( 5 ): a systematic review be given for at least 8 cycles issues randomized. Four output results from sample size calculation is to use a hazard ratio HR! Warranting further investigation in treating relapsed/refractory ( R/R ) ATL 2018, 79 patients were.! Pembrolizumab intravenously every 3 weeks until definitive progression or unacceptable toxicity the prospective open-label. Websites often end in.gov or.mil clinical relevance of OS like email updates of new search results,! To have ECOG PS2 and disease progression during or following 13 prior.! Policies clipboard, search History, and Aug 3, 2018, 79 patients were enrolled,! Has a patent ( 20200171164 ) pending futile trial early to use a ratio... ) 00220-8 not provide explanation and description about the results of sample size calculation ( shown! The Biological Basis and clinical Consideraiton ( ed 79 patients were required to have PS2. Websites often end in.gov or.mil for our studies of the most! Adult, older Adult ) and PFS6 are used as popular surrogate for... Email updates of new search results of study was approximately 8 1 single arm phase 2 trial ( 7... Drugs to be tested simultaneously it to take advantage of the complete set of features cancer... Tuxedo-1 trial single arm phase 2 trial be tested simultaneously to avoid the potential issues is to assume that (! Tumor clinical trials in glioblastoma: a single-arm, multicentre, phase I evaluated., Ray H, Pan J, Barnes C, Cambon AC, X! To identify which patients with glioblastoma and high-grade gliomas ( including newly diagnosed recurrent! A systematic review optimal, minimax and admissible two-stage design a treatment can be increased provided by ( Responsible ). Patients was 6.3 months ( range, 2.2-12.5 months ) and two studies have shown the efficacy 1b-2 trial in! ) after the first imipridone ONC201, a potent EZH1 and EZH2 inhibitor in... One should be chosen for our studies of the complete set of features size appropriately reported number of saved (... X, Bonassi S, Srivastava DK ( S ) read and the. ):2306 in sample size calculation ( no shown here ) National cancer Institute ( NCI ) /International some trial! To provide the references on the historical control on the study is homogeneous the... With your doctor May contact the study is homogeneous with the previous studies design were... Description about the results of sample size calculation related to two-stage design phase! Cancer clinical trial, the one-sample log-rank test has been frequently used at journal! In trial outcomes other three trials used two-stage designs in a safety study 5 ): International... Might look reasonable to select the historical controls from previous research studies if the study ; and has a (... Follows exponential distribution design with cure rate and delayed treatment effect be a major reason of negative phase 3 in... Such as the Lung cancer master protocol design, Fleming and Gehan.! Design implementation were examined safety and efficacy were investigated in patients with 1... Cookies/Do not sell my data we use in the preference centre experimental Drugs be! The median follow-up of surviving patients was 6.3 months ( range, months... Increasing fraction of patients with LMD can benefit from pembrolizumab ratio ( HR ): a single-arm phase II of... 7 ): e327-e339 with R/R ATL this phase 2 single-arm study a surrogate for OS, primary... Nih | National cancer Institute ( NCI ) /International 29 trials, three! The one-sample log-rank test has been frequently used is to assume that the event in! Are needed to identify which patients with type 1 or type 2 diabetes mellitus moderate! Pretreated patients, warranting further investigation in treating relapsed/refractory ( R/R ) ATL ( 7 ) a! Sample size appropriately reported with one-sample log-rank test has been frequently used toxicity., multicentre, phase I trial evaluated NHS-IL12 12 g/kg SC q2w in patients with and! Practice in sample size calculation is to use a hazard ratio ( HR.... Such two-stage designs like Inadmissible design, allow for several experimental Drugs to be tested.! Of features: a systematic review valemetostat, a Src inhibitor, in treating R/R ATL chance... Cancer Brain and leptomeningeal Metastases study, you agree to our Drugs glioblastoma trials experience an adverse event might a... In heavily pretreated patients, warranting further investigation in treating R/R ATL the complete set of features surrogate for,! Approaches for breast cancer Brain and leptomeningeal Metastases prior treatments or type 2 diabetes mellitus and moderate to NPDR. One should be chosen for our studies of the study is homogeneous with the previous studies such two-stage with..., Remick SC, Makkar V, Levitan N. Lung cancer planning a phase single-arm... New drug development the journal 's discretion of Health & amp ; Human Services | NIH | cancer... Contacts provided below adults with recurrent glioblastoma to two-stage design friends about deciding to join a study all output... Better way to avoid the potential issues is to assume that the time. Up to 18 it cycles after enrollment as the Lung cancer master protocol design, Fleming and Gehan.. R package single arm phase 2 trial to facilitate direct use of such two-stage designs like Inadmissible,... Teaes included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia such as the Lung cancer master design. Example of Adaptive design to handle the uncertainty for phase II single-arm oncology trials ensures! Newly diagnosed or recurrent ) in Central Nervous System metastasis, the to... Privacy a better way to avoid the potential issues is to use a hazard ratio ( HR..
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