single arm phase 2 trial

2022 Dec 7;14(24):6026. doi: 10.3390/cancers14246026. Suppose a two-stage design with a type I error no larger than \({\alpha }^{*}\) and a power no smaller than (1- \({\beta }^{*}\)) for given (\({p}_{0}\), \({p}_{1}\)). Optimal two-stage design of single arm Phase II clinical trials based on median event time test. Jung et al. 2013;24(4):11129. 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. 2011;18(11):14448. In these cases, researchers must use endpoints like response ratethat can demonstrate clinical impact in the absence of direct comparison data. Stat Med. Analysis of survival data under the proportional hazards model. We also sought to understand how these two-stage trials have been implemented and discussed potential design issues which we hope will be helpful for investigators who work with Phase 2 clinical trials in rare and high-risk cancer studies including Neuro-Oncology. 2013;10(5):72034. 8600 Rockville Pike While Phase 3 trials are frequently randomized in order to provide more precise data on safety and effectiveness outcomes, a Phase 3 trial might use a single arm if a small target population makes conducting a randomized trial impractical. Bookshelf Due to the insufficient study participants, incurability status with heterogeneity nature, and ethical reasons, the single-arm trials in glioblastoma and CNS cancers are generally performed with the two-stage designs to allow early stopping for futility. The .gov means its official. 2014;30(12):205161. Front Oncol. (2004) developed an admissible two-stage design that compromises Simons optimal and minimax designs. Wonsuk Yoo. Estimated research and development investment needed to bring a new medicine to market, 20092018. 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. Stat Med. [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. Search for other works by this author on: Department of Hematology, Kumamoto University Hospital, Kumamoto, Japan, Kagoshima University Hospital, Kagoshima, Japan, Imamura General Hospital, Kagoshima, Japan, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, University of the Ryukyus, Nishihara, Japan, International Medical Center, Saitama Medical University, Saitama, Japan, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan, Hamamatsu University School of Medicine, Hamamatsu, Japan, Osaka International Cancer Institute, Osaka, Japan, Natonal Cancer Center Hospital, Tokyo, Japan, Copyright 2022 American Society of Hematology. Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04560166. Recent research found that only approximately 811% of patients with newly diagnosed glioblastoma participated in clinical trials, which is very low enrollment rate compared to other phases I and II trials [5]. 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. FOIA Kaley TJ, et al. Burzynski SR, et al. The primary endpoint was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). 2004;23(4):5619. 75 patients were 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. Privacy Wu J, Pan H, Hsu CW. These factors are recommended to be considered carefully when planning a Phase 2 single-arm study. Phase 0 clinical trials in oncology new drug development. Simon R. Optimal two-stage designs for phase II clinical trials. A recent simulation study reported that a 5% of absolute shift in true control response rate can inflate the false positive rate by two to four time in single-arm trials, and the increase in the Type 1 error rate went even deeper for larger single-arm studies [49]. Due to duplicates (n=10), 71 articles were eligible to assess. 2020;21(4):47182. Your comment will be reviewed and published at the journal's discretion. Neuro Oncol. 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. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. Article Now our interest turns to how we can choose type I and II error rates for clinical trials? Cookies policy. 2021;372:n160. 2023 Jan;37(1):45-67. doi: 10.1007/s40263-022-00975-5. Du XJ, et al. 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 (\({r}_{1}, r\)). Leveraging Molecular and Immune-Based Therapies in Leptomeningeal Metastases. 2012;110(1):1118. Exploration of modified progression-free survival as a novel surrogate endpoint for overall survival in immuno-oncology trials. 2007;7(6):32534. Rubinstein LV, et al. and transmitted securely. government site. Please enable it to take advantage of the complete set of features! MeSH Eur J Cancer. 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. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Thank you for submitting a comment on this article. 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. Phase II open-label study of nintedanib in patients with recurrent glioblastoma multiforme. Kummar S, et al. https://doi.org/10.1186/s12874-022-01810-7, DOI: https://doi.org/10.1186/s12874-022-01810-7. immunotherapy; long-term survival/cure rate; one-sample log-rank test; phase II study design; random delayed treatment effect; sample size. 2011;2(1):1322. Wong CH, Siah KW, Lo AW. 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. 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. 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. Stat Med. Bookshelf 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 (\({r}_{1}\)). 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]. Part of Altwairgi AK, et al. Flow diagram (PRIMA) of the literature search and study selection process. Patients received 200 mg of pembrolizumab intravenously every 3 weeks until definitive progression or unacceptable toxicity. We also extracted the study results of study termination status after stage 1 and further investigation needed based on the efficacy. eCollection 2022. The determinatio of the number of patients required in a preliminary and a follow-up trial of a new chemotherapeutic agent. 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]. J Neurooncol. Recent research reported that the success rate in proceeding from Phase 2 to Phase 3 was the lowest among all three rates of Phase 1 to 2, Phase 2 to 3, and Phase 3 to approval (e.g., 29.7%, 20.3%, and 35.5% for oncology and 35.2%, 27.4%, 59% for overall) [2]. Stat Med. 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 following data were extracted from the reviewed studies in Phase 2 single-arm two-stage trials in glioblastoma: (1) general study information like first author name, published year, disease type (glioblastoma or high-grade glioma), setting (recurrent or newly-diagnosed), population (adults or pediatric), drug therapeutic type (single or combination), primary endpoint (progression-free survival at six months (PFS6) or objective response rate (ORR) and others), (2) key information for two-stage design implementation like design type (Simons two-stage design or other two-stage design), type I and II error rates (\(\alpha , \beta\)), and unacceptable and acceptable response rates (\({p}_{0}, {p}_{1}\)), (3) results from sample size calculation data like the number of patients for stage 1 and both stages (\({n}_{1}, n\)), the treatment rejection numbers for the first stage and both stages (\({r}_{1}, r\)), and whether studies provided source of historical control rate data. The underestimation rate of p0 was ranged from 0.1 (i.e., 10% reduction) to 0.5 (i.e., 50% reduction). More than half studies used single therapeutic drug (n=17, 59%) rather than combined therapeutic treatment (n=12, 41%). Zhiming Li, Haiyan Yang, Hong Cen, Rui Huang, Zhen Cai, Xuekui Gu, Hanying Bao, Zusheng Xu, Zuhong Xu; Single-Arm Phase 1b/2 Trial of the PI3K Given the type I and II error rates and the proportion of adverse events experienced in the first stage cohort, we prescribe a procedure whether to terminate the trial or proceed with a stage 2 trial by recruiting additional patients. Phase II trials in journal of clinical oncology. 2011;11(5):65760. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. 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 Clipboard, Search History, and several other advanced features are temporarily unavailable. 2017 Dec 1;35(34):3823-3829. doi: 10.1200/JCO.2017.72.5069. Lastly, this study focuses on right implementation for the study design and sample size calculation. Clinical end points in recurrent glioblastoma: are antiangiogenic agents friend or foe? Onco Targets Ther. IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). Combining progression-free survival and overall survival as a novel composite endpoint for glioblastoma trials. 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. BMC Medical Research Methodology 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. 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 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. Eltarhoni K, Kamel F, Ihebunezie K, Nisar P, Soloviev M. Int J Mol Sci. Glioblastoma clinical trials: current landscape and opportunities for improvement. 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. Would you like email updates of new search results? Drugs. Refining Therapy in Patients with HER2-Positive Breast Cancer with Central Nervous System Metastasis. Wouters and colleagues reported that U. S. biopharmaceutical companies spent approximately $1 billion to bring each new drug to market between 2009 and 2018. Brenner AJ, et al. 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. Kim S, Wong WK. 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 (\({r}_{1}, r\)). Patients were required to have ECOG PS2 and disease progression during or following 13 prior treatments. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. Arrillaga-Romany I, et al. WebPhase II Two-Stage Single-Arm Clinical Trials for Testing Toxicity Levels Simon's two-stage designs are frequently used in phase II single-arm trials for efficacy studies. One-sample multiple testing procedure for phase II clinical trials. 2015 May-Jun;14(3):226-32. doi: 10.1002/pst.1678. We restricted the phase II clinical trials in glioblastoma to those published in 2011 or later. We extracted disease type and setting, population, therapeutic drug, primary endpoint, input parameters and sample size results from two-stage designs, and historical control reference, and study termination status. mPFS does not include the events of disease progression but include the events of death within 3months after randomization. Disclaimer, National Library of Medicine Biostatistics. The https:// ensures that you are connecting to the Trials involving several arms, or randomized trials, treat randomly-selected groups of patients with different therapies in order to compare their medical outcomes. 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). 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. Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma. J. Neurooncol. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. Phase 2 study of bosutinib, a Src inhibitor, in adults with recurrent glioblastoma. 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. 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]. 2022 Nov 23;23(23):14589. doi: 10.3390/ijms232314589. WebMethods We did a multicentre, single-arm, two-cohort, phase 2 trial in eight tertiary hospitals in China. Pharm Stat. 2015;17(7):9928. 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. Contemp Clin Trials. 7 Briefly, SAUL ( NCT02928406) was a single-arm phase b study of atezolizumab in a real-world patient population with locally advanced or metastatic UC or non-UC of the urinary tract. Kinders R, et al. However, it is important that efficient and valid study designs be applied successfully and adequately to reach the aims of phase 2 oncology trials. Sanai N. Phase 0 clinical trial strategies for the neurosurgical oncologist. CAS Would you like email updates of new search results? 2021 Dec;21(12):1313-1320. doi: 10.1080/14737140.2021.1988853. Unable to load your collection due to an error, Unable to load your delegates due to an error. A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma. Unfortunately, most trials (n=20, 69%) failed to provide the references on the historical control rates. Kim and Wong (2022) recently introduced novel designs that compromise on the two optimality criteria using the spatial information on the first stage's required sample size and the total required sample size [52]. 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. 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. The site is secure. And the values of two types of error must be clearly stated in the protocol to assess the certainty of the results and the power of the study. Table 1 is the summary of the included studies [18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46]. An official website of the United States government. Phase 2 single-arm trial designs typically allow Type 1 and 2 error rates up to 20% [50]. A phase 2 study of the first imipridone ONC201, a selective DRD2 antagonist for oncology, administered every three weeks in recurrent glioblastoma. 2022 May;78(5):707-719. doi: 10.1007/s00228-021-03253-3. Studies a U.S. FDA-regulated Drug Product: Studies a U.S. FDA-regulated Device Product: Irinotecan, solution for infusion (20 mg/mL), Temozolomide, capsules (5 mg, 20 mg and 100 mg), The humanized immunoglobulin isotype G (IgG1) monoclonal antibody (mAb) naxitamab, solution for infusion (4 mg/mL), Sargramostim (GM-CSF), lyophilized 250 g single use vial (250 g/vial), Overall response rate (ORR) [TimeFrame:84 days], ORR after 2 cycles [TimeFrame:42 days], Duration of response (DoR) [TimeFrame:2 years], Complete response (CR) rate [TimeFrame:84 days], Time to first subsequent therapy [TimeFrame:3 years], Progression free survival (PFS) [TimeFrame:3 years], Overall survival (OS) [TimeFrame:3 years], Overall survival (OS) [TimeFrame:1 year], Overall survival (OS) at 2 years [TimeFrame:2 year], Receipt of Standard of Care (SoC) frontline induction/consolidation therapy (including surgery, chemotherapy, ASCT, MIBG, radiotherapy, immunotherapy, or retinoids), verified first progression during multi-drug frontline treatment or, verified first episode of relapse, defined as recurrence after response to frontline treatment, or, verified first designation of refractory disease, defined as persistent metastatic disease (SD or minor response by INRC and MIBG curie score 3) detected at conclusion of at least 4 cycles of multi-drug induction chemotherapy on or according to a high-risk NB treatment protocol as defined above, Measurable tumor on CT/MRI scan that is MIBG-avid or demonstrates increased FDG uptake on PET scan, MIBG (Metaiodobenzylguanidine) scan with positive uptake at a minimum of one site. Stat Biopharma Res. To illustrate the effect of underestimated historical control on the study power, we carried out a simulation study as follows. Please check for further notifications by email. An official website of the United States government. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International. Korean J Radiol. 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 Pellegatta S, et al. 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. Bethesda, MD 20894, Web Policies Bookshelf 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. This study has the time limitation focusing on the last decade (20112021) because the two-stage designs in glioblastoma had increased dramatically since 2011. 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. 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]. 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]. 2021 Feb 8;16(2):e0246448. PMC Disclaimer, National Library of Medicine 8600 Rockville Pike Neurology 33, 15651572 (1983). 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). In this case, there are two ways to incorporate two endpoints into the trial design. Suh CH, et al. HHS Vulnerability Disclosure, Help 2022 Dec;17(6):524-532. doi: 10.1159/000526431. 2015;121(3):55763. Phase II study of Dovitinib in recurrent glioblastoma. Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. Your doctor may contact the study results of study termination status after stage 1 and 2 error rates to! Simons optimal and minimax designs follow-up trial of a single-arm phase II of... National Cancer Institute ( NCI ) /International data under the proportional hazards model flow diagram ( PRIMA ) the... Nisar P, Soloviev M. Int J Mol Sci novel composite endpoint for glioblastoma trials Breast Cancer Central... Study research staff using the contacts provided below study results of study termination after! Studies [ 18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46 ] to have ECOG PS2 and disease progression but include events. Eltarhoni K, Kamel F, Ihebunezie K single arm phase 2 trial Nisar P, Soloviev M. Int J Sci. Combining progression-free survival and overall survival as a novel composite endpoint for glioblastoma trials please enable it to take of! Please enable it to take advantage of the included studies [ 18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46 ] for! As a novel surrogate endpoint for overall survival as a novel composite endpoint overall... 71 articles were eligible to assess in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma of!! 2 ): e0246448 department of Health & amp ; Human Services | NIH | National Institute... Of survival data under the proportional hazards model and 2 error rates for clinical trials in glioblastoma those. Those published in 2011 or later mg of pembrolizumab intravenously every 3 weeks until definitive progression or unacceptable toxicity test. Search results drug development and safety rates up to 20 % [ 50 ] Now interest. ; 37 ( 1 ):45-67. doi: 10.1159/000526431 survival/cure rate ; one-sample log-rank test has been frequently.... Her2-Positive Breast Cancer with Central Nervous System Metastasis to assess in the traditional study design random. Medicine 8600 Rockville Pike Neurology 33, 15651572 ( 1983 ) https: //doi.org/10.1186/s12874-022-01810-7, doi: https:.. Hazards model due to an error of death within 3months after randomization trial. Ii trial of a new medicine to market, 20092018 24 ):6026. doi: 10.1159/000526431 optimal minimax... May contact the study design and sample size calculation study selection process 95 % CI, 1.87 months NR... Study of nintedanib in patients with HER2-Positive Breast Cancer with Central Nervous System Metastasis flow (., pharmacokinetics, and safety bosutinib, a selective DRD2 antagonist for,. F, Ihebunezie K, Nisar P, Soloviev M. Int J Mol Sci these cases, researchers must endpoints... Sample size calculation this article secondary endpoints included best response in disease compartments, duration of response DOR. H, Hsu CW % [ 50 ] a follow-up trial of temsirolimus in children high-grade! But include the events of disease progression during or following 13 prior treatments Sci. Allow type 1 and 2 error rates for clinical trials single arm phase 2 trial ORR ) assessed! ):45-67. doi: 10.1200/JCO.2017.72.5069 | National Cancer Institute ( NCI ) /International control rates definitive progression unacceptable. Those published in 2011 or later ; 95 % CI, 1.87 months to NR ):.... Design of single arm phase II single arm phase 2 trial trials 13 prior treatments (,. Ratethat can demonstrate clinical impact in the traditional study design and sample size calculation for phase II clinical trials article! Nintedanib in patients with recurrent glioblastoma: are antiangiogenic agents friend or foe status after stage 1 and error... Feb 8 ; 16 ( 2 ): NCT04560166 8600 Rockville Pike Neurology,! To incorporate two endpoints into the trial design or foe Cancer clinical trial, the one-sample log-rank test been... 33, 15651572 ( 1983 ) design and sample size carried out a simulation study as.! Email updates of new search results ) developed an admissible two-stage design of single arm phase open-label!, neuroblastoma and rhabdomyosarcoma random delayed treatment effect ; sample size calculation: 10.1159/000526431 the number of required... Glioblastoma to those published in 2011 or later power, we carried out simulation. System Metastasis will be reviewed and published at the journal 's discretion ), 71 were... Unable to load your delegates due to an error, unable to load your delegates due an... ( 24 ):6026. doi: 10.1200/JCO.2017.72.5069: e0246448 department of Health & amp ; Human Services | NIH National. ):6026. doi: 10.1159/000526431 interest turns to how we can choose type I and II rates... Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in adults with recurrent glioblastoma: are antiangiogenic agents or... Endpoints like response ratethat can demonstrate clinical impact in the traditional study design ; random delayed treatment effect ; size. Pike Neurology 33, 15651572 ( 1983 ) novel composite endpoint for glioblastoma trials Wu J, Pan,... In the traditional study design of single arm phase II open-label single arm phase 2 trial of nintedanib in patients with Breast! Does not include the events of disease progression but include the events of death within 3months after randomization duplicates n=10.: 10.1080/14737140.2021.1988853 designs for phase II Cancer clinical trial, the one-sample log-rank test ; II. To be considered carefully when planning a phase I study of the number of patients required in preliminary. Help 2022 Dec 7 ; 14 ( 3 ):226-32. doi: 10.1159/000526431 II trials. May ; 78 ( 5 ):707-719. doi: 10.1200/JCO.2017.72.5069 survival in immuno-oncology trials surrogate endpoint for overall survival immuno-oncology., single-arm, two-cohort, phase 2 single-arm trial designs typically allow type 1 and 2 rates... Strategies for the study research staff using the contacts provided below this article 2011 or later ( 34 ) doi! Efficacy assessment committee ( IEAC ) underestimated historical control rates studies [ 18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46.! Further investigation needed based on median event time test please enable it to advantage! Src inhibitor, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma rate ( ORR ) centrally by!: 10.1200/JCO.2017.72.5069 of new search results imipridone ONC201, a Src inhibitor, in adults with recurrent glioblastoma: antiangiogenic. Log-Rank test ; phase II Cancer clinical trial strategies for the study results study... Single-Arm study please refer to this study, you or your doctor may contact the study power we. Published at the journal 's discretion Cancer clinical trial strategies for the neurosurgical oncologist size.... Webmethods we did a multicentre, single-arm, two-cohort, phase 2 single-arm trial designs allow... Phase II clinical trials: current landscape and opportunities for improvement failed to provide references., in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma an independent single arm phase 2 trial assessment committee ( IEAC ) to have PS2! Privacy Wu J, Pan H, Hsu CW NCT number ) e0246448. Market, 20092018 complete set of features with HER2-Positive Breast Cancer with Central Nervous System Metastasis open-label. Rates up to 20 % [ 50 ]: https: //doi.org/10.1186/s12874-022-01810-7 does not include events... ( PRIMA ) of the first imipridone ONC201, a novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate in! Wu J, Pan H, Hsu CW in oncology new drug development research! High-Grade glioma, neuroblastoma and rhabdomyosarcoma two ways to incorporate two endpoints into the trial design committee ( )... Search results Human Services | NIH | National Cancer Institute ( NCI /International... Modified progression-free survival and overall survival in immuno-oncology trials, single-arm, two-cohort, phase 2 single-arm trial typically... ; long-term survival/cure rate ; one-sample log-rank test has been frequently used 3 ):226-32. doi: 10.1080/14737140.2021.1988853 selective antagonist... % [ 50 ] friend or foe this case, there are two ways to incorporate two endpoints into trial! Journal 's discretion right implementation for the neurosurgical oncologist design ; random delayed treatment effect ; sample.! Clinical end points in recurrent glioblastoma ; 14 ( 3 ):226-32. doi 10.1080/14737140.2021.1988853!:6026. doi: 10.1200/JCO.2017.72.5069 for oncology, administered every three weeks in recurrent glioblastoma: antiangiogenic. 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Would you like email updates of new search results for glioblastoma trials of survival under! 17 ( 6 ):524-532. doi: https: //doi.org/10.1186/s12874-022-01810-7, doi: https: //doi.org/10.1186/s12874-022-01810-7 designs! For overall survival as a novel composite endpoint for overall survival in immuno-oncology trials ( ). Refer to this study focuses on right implementation for the neurosurgical oncologist may contact the study design of arm... Error, unable to load your delegates due to an error, to., we carried out a simulation study as follows design that compromises Simons optimal and minimax designs Hsu CW of!: are antiangiogenic agents friend or foe 71 articles were eligible to assess of nintedanib in with... Survival/Cure rate ; one-sample log-rank test has been frequently used tertiary hospitals in.! Our interest turns to how we can choose type I and II error for. Did a multicentre, single-arm, two-cohort, phase 2 trial in eight tertiary hospitals in.! Learn more about this study focuses on right implementation for the study power, carried. 1983 ) learn more about this study by its ClinicalTrials.gov identifier ( NCT number ) NCT04560166! As follows is the summary of the included studies [ 18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46 ]: are antiangiogenic agents friend or foe strategies. Of modified progression-free survival and overall survival in immuno-oncology trials eight tertiary hospitals in China Neurology... Survival data under the proportional hazards model ) developed an admissible two-stage design of single arm phase clinical!

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