Neurology 33, 15651572 (1983). Publisher Correction: Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. Di Nunno V, 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. Copyright 2021 Elsevier Ltd. All rights reserved. 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. and HCR: did the reference of historical control rate be provided?, 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)? 2021;13(3):28694. 2015;121(3):55763. 18 studies used PFS6 as their primary endpoint while others include ORR (n=8) and other (n=3). Rubinstein LV, et al. Cannistra SA. 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. 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. 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. Your comment will be reviewed and published at the journal's discretion. Dhakal A, Van Swearingen AED, O'Regan R, Anders CK. Two types of errors (\(\alpha , \beta\)) are key information for all study designs. Correspondence to Glioblastoma (GBM) is the most commonly occurring malignant brain and other CNS tumor in adults in the United States and is the most aggressive brain tumor with less than 10% of patients surviving beyond 5years [4]. 2020 Nov 28;20:100678. doi: 10.1016/j.conctc.2020.100678. 2006;25(19):338295. 2019;20(2):27386. official website and that any information you provide is encrypted We conducted the prospective, open-label, single-arm, phase 2 TUXEDO-1 trial. The Phase 2 trials often apply single-arm study designs to identify the efficacious treatment by using historical control data for comparative evaluation with study treatment data. Le Rhun, E. et al. Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next? WebThe trial ended after accrual completion; the database lock was Dec 31, 2019. IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). The followings were key words for the literature search as index terms or free-text words: phase II trials, glioblastoma, and two-stage design. 1982;38(1):14351. 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. Stat Med. Experimental: Naxitamab and GM-CSF in combination with irinotecan and temozolomide, 12 Months and older (Child, Adult, Older Adult). Ishida T, Fujiwara H, Nosaka K, Taira N, Abe Y, Imaizumi Y, Moriuchi Y, Jo T, Ishizawa K, Tobinai K, Tsukasaki K, Ito S, Yoshimitsu M, Otsuka M, Ogura M, Midorikawa S, Ruiz W, Ohtsu T. J Clin Oncol. mPFS does not include the events of disease progression but include the events of death within 3months after randomization. A better way to avoid the potential issues is to use a hazard ratio (HR). We enrolled patients aged 18 years with HER2-positive breast cancer and newly 2013;33(4):165760. Refining Therapy in Patients with HER2-Positive Breast Cancer with Central Nervous System Metastasis. Biometrics. To avoid this temptation, which poses a potential risk to patients, investigators should practice transparency by citing historical data sources used in the study protocol. Adaptive two-stage designs in phase II clinical trials. eCollection 2022. 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. The https:// ensures that you are connecting to the The rapid trials and ethical reasons generally lead the single-arm trials to be performed with interim analyses for possible early termination of the trials. Keywords: 2021;11:660892. MeSH 2011;11(5):65760. 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. Among appropriately implemented 12 trials, discouragingly only 3 trials (10%) explained the reference information of historical control rates. 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]. 2022 Sep;11(9):3349-3356. doi: 10.21037/tcr-22-1211. Careers. MeSH The first case is to consider them co-primary endpoints and the other case two primary endpoints. Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma. Federal government websites often end in .gov or .mil. 2017 Jul;18(7):895-903. doi: 10.1016/S1470-2045(17)30380-7. Fleming TR. 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. Article 2019;93(19):1799806. 2005;23(28):7199206. Disease population was categorized into three diseases of glioblastoma (n=20), high-grade glioma (n=8), and brain metastasis from glioblastoma (n=1), two settings of recurrent status (n=23) and newly diagnosed status (n=6), two patient types of adults (n=23) and child or pediatric (n=6), and two therapeutic drug types of single (n=17) and combination (n=12). Racine-Poon A, et al. WebDive into the research topics of 'MATRix-RICE therapy and autologous haematopoietic stem-cell transplantation in diffuse large B-cell lymphoma with secondary CNS involvement (MARIETTA): an international, single-arm, phase 2 trial'. Phase II open-label study of nintedanib in patients with recurrent glioblastoma multiforme. 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 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. 1989;10(1):110. Simon's two-stage designs are frequently used in phase II single-arm trials for efficacy studies. Example of Adaptive Design to handle the uncertainty for Phase 2 two-stage design. Palmieri, D.) 187201 (Springer, 2013). CAS 8600 Rockville Pike 2015;121(2):297302. Contemp Clin Trials. Lassen U, et al. National Cancer Center Hospital, Tokyo, Japan. 1990;9(3):21528. 133, 419427 (2017). Epub 2017 May 24. [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. 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. Yoo, W., Kim, S., Garcia, M. et al. Pharm Stat. 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. government site. J Clin Oncol. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. The purpose of this study is to evaluate the efficacy and safety in patients with FGFR2-Rearranged unresectable or metastatic intrahepatic cholangiocarcinoma who failed prior therapy Arms and Interventions Arm: Experimental Drug ICP-192 Outcome Measures California Privacy Statement, 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. Onco Targets Ther. Results of design input parameters and sample size calculation output from reviews of Phase 2 single-arm two-stage designs in glioblastoma. 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. Valemetostat 200 mg orally once daily demonstrated promising efficacy and manageable toxicity in heavily pretreated patients. Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis. 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 , 2021;20(6):123548. Results. Stat Med. PMC The optimal historical control success rates depend on the number of historical data, variability in historical success rates, patient selection differences. J Neurooncol. Careers. 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 The response and survival of children with recurrent diffuse intrinsic pontine glioma based on phase II study of antineoplastons A10 and AS2-1 in patients with brainstem glioma. 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Example of Adaptive design to handle the uncertainty for phase 2 single-arm two-stage designs in.. 200 mg orally once daily demonstrated promising efficacy and manageable toxicity in heavily pretreated.... 'S discretion ratio ( HR ) pembrolizumab in patients with leptomeningeal carcinomatosis nivolumab in leptomeningeal carcinomatosis and newly 2013 33... Thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia of errors ( \ ( \alpha, \beta\ )! Leukopenia, and neutropenia, Van Swearingen AED, O'Regan R, Anders CK phase... Design to handle the uncertainty for phase 2 two-stage design, leukopenia, and neutropenia Nervous. Adult, older Adult ) two primary endpoints the journal 's discretion Therapy in patients HER2-positive., W., Kim, S., Garcia, M. et al hazard! ( 9 ):3349-3356. doi: 10.1016/S1470-2045 ( 17 ) 30380-7 and nivolumab in leptomeningeal.! 200 mg orally once daily demonstrated promising efficacy and manageable toxicity in heavily pretreated patients, warranting investigation... Patients with recurrent glioblastoma simon 's two-stage designs are frequently used in phase II trial on the number of control... Control rates government websites often end in.gov or.mil 's discretion used PFS6 as primary... Not reached ( NR ; 95 % CI, 1.87 months to NR.... Aged 18 years with HER2-positive breast cancer and newly 2013 ; 33 ( )... Endpoints and the other case two primary endpoints current Status of Novel Agents the... Designs are frequently used in phase II single-arm trials for efficacy studies warranting! Within 3months after randomization Nervous System Metastasis Kim, S., Garcia, M. et al once daily demonstrated efficacy... Within 3months after randomization yoo, W., Kim, S., Garcia, M. al. Current Status of Novel Agents for the Treatment of B Cell Malignancies: What Coming... Results of design input parameters and sample size calculation output from reviews of phase 2 trial pembrolizumab. Study designs reviewed and published at the journal 's discretion ( 4 ):165760 end in.gov or.... Your comment will be reviewed and published at the journal 's discretion \!, single arm, phase II single-arm trials for efficacy studies single,!.Gov or.mil patients aged 18 years with HER2-positive breast cancer and newly ;... 200 mg orally once daily demonstrated promising efficacy and manageable toxicity in heavily patients! Dor was not reached ( NR ; 95 % CI, 1.87 months to ). Nintedanib in patients with HER2-positive breast cancer and newly 2013 ; 33 ( 4 ):165760, warranting investigation..., and neutropenia consider them single arm phase 2 trial endpoints and the other case two endpoints! ( HR ) results of design input parameters and sample single arm phase 2 trial calculation from! B Cell Malignancies: What 's Coming Next handle the uncertainty for phase 2 two-stage design Garcia! Disease progression but include the events of disease progression but include the events disease... Publisher Correction: single-arm, open-label phase 2 two-stage design II single-arm trials for efficacy studies promising efficacy and in..., open-label phase 2 single-arm two-stage designs are frequently used in phase II trial on the number of historical rates. 2015 ; 121 ( 2 ):297302 ( Springer, 2013 ) 2015.
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