The author(s) read and approved the final manuscript. Furthermore, only 3 trials (10%) provided appropriate information for key input and output data as well as references information of historical control rates. Sharma M, et al. 133, 419427 (2017). An official website of the United States government. 2021;20(6):123548. Glioblastoma clinical trials: current landscape and opportunities for improvement. 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)? The sample size calculation for the two-stage designs is determined based on the historical control rate and difference between the two rates (\({p}_{0}, {p}_{1}\)). Publisher Correction: Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. 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. Phase 0 clinical trials: recommendations from the task force on methodology for the development of innovative cancer therapies. Br J Cancer. Zhou H, 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. WebEVER-132-001 (NCT04454437) was a multicenter, single-arm, Phase IIb study in Chinese patients with mTNBC who failed 2 prior chemotherapy regimens. 2020 Jul;21(7):978-988. doi: 10.1016/S1470-2045(20)30225-4. J. Neurooncol. Diffuse Large B-Cell Lymphoma (DLBCL): Early Patient Management and Emerging Treatment Options. Transparency comes from providing information on historical control rates borrowed from the literature as well as expected response rates from the experimental agent. 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. Yoo, W., Kim, S., Garcia, M. et al. 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]. 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. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. In other words, we might encounter the variability in the historical controls for comparison, which substantially inflates the Type 1 error rate or false-positive error rate and may lead to erroneous conclusions. 2021 Jun;22(6):741-742. doi: 10.1016/S1470-2045(21)00191-1. Chu Y, Yuan Y. The synonyms and closely related words include phase 2 for phase II trials, GBM or high-grade glioma for glioblastoma, and 2-stage, Simon, Fleming or Gehan for two-stage design. Int Stat Rev/Revue Int de Stat. Pharm Stat. Fortunately, several reviews present that PFS6 and OS are generally strongly associated in glioblastoma trials, but not between RR and OS [54]. 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. Brastianos, P.K., Brastianos, H. & Eichler, A.F. Most frequently used population was adult patients with recurrent glioblastoma. 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 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]. J Neurooncol. Murgo AJ, et al. Neuro Oncol. Epub 2022 Apr 1. Information provided by (Responsible Party): An International, Single-Arm, Multicenter Phase 2 Trial. Article Unable to load your collection due to an error, Unable to load your delegates due to an error. Brenner AJ, et al. Gehan EA. Epub 2019 Feb 11. Bookshelf Control Clin Trials. Clin Cancer Res. The PFS at 6months (PFS6) is the most widely used endpoint in glioblastoma trials because of reflection of the rate of cases of durable disease control [58]. Results. 2007;7(6):32534. 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 PMC Oncotarget. eCollection 2019 Jul 2. There has been the need for new two-stage designs that allow flexible modification of design parameters under the control of the Type 1 error, which is called adaptive design methods to perform arbitrary design modification under the control of the Type 1 error rate. 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. CC-S reports grants from ADC Therapeutics, during the conduct of the study; and grants from Rhizen Pharmaceuticals, and personal fees from Servier, Novartis, Genenta Science, ADC Therapeutics, Roche, Boehringer Ingelheim, Sanofi, Karyopharm, Bristol-Myers Squibb, Merck Sharp & Dohme, Janssen Oncology, and AstraZeneca, outside of the submitted work. Expert Rev Anticancer Ther. 2020;22(12 Suppl 2):iv196. A Simon two-stage design was used to compare a null hypothesis OS3 of 18% against an alternative of 43%. Using volume22, Articlenumber:327 (2022) Tawbi HA, et al. J Clin Oncol. Phase 2 single-arm trial designs typically allow Type 1 and 2 error rates up to 20% [50]. 2022 May;78(5):707-719. doi: 10.1007/s00228-021-03253-3. 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. Here, we performed a complete systematic review on the phase 2 single-arm two-stage trials in glioblastoma to evaluate the appropriate application of the two-stage designs. Results of design input parameters and sample size calculation output from reviews of Phase 2 single-arm two-stage designs in glioblastoma. Du XJ, et al. There is no universal solution to handle the variability around historical control data since the selected design depends on judgements to the specific study circumstances. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Gupta UC, et al. 2019;37(15_suppl):1820618206. The optimal historical control success rates depend on the number of historical data, variability in historical success rates, patient selection differences. 2016 Dec;34(34):4086-4093. doi: 10.1200/JCO.2016.67.7732. 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 government site. J Neurooncol. An official website of the United States government. 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). Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. 2020;20(1):126. 2017;36(21):330214. Second, given the limited number of available single-arm two-stage trials, the results in these studies are subject to specific degree of selection criteria. The outcomes of simulation are depicted in Fig. 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. Phase II study of sunitinib malate in patients with recurrent high-grade glioma. Example of Adaptive Design to handle the uncertainty for Phase 2 two-stage design. 2022 Dec 9;2022(1):146-154. doi: 10.1182/hematology.2022000332. The primary endpoint was safety. Analysis of survival data under the proportional hazards model. 2014;30(12):205161. Clinical end points in recurrent glioblastoma: are antiangiogenic agents friend or foe? Single-arm phase II trial design under parametric cure models. The therapeutic areas in oncology and immune-modulatory drugs were the most expensive, with a median of $2.8 billion and a mean of $4.5 billion [3]. PMC 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. Multicenter Phase II Study of Lenalidomide in Relapsed or Recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002. 18 studies used PFS6 as their primary endpoint while others include ORR (n=8) and other (n=3). 2017;131(3):60310. Oncol Lett. Fangusaro J, et al. Batista MFFV, Eiriz I, Fitzpatrick A, Le Du F, Braga S, Alpuim Costa D. Breast Care (Basel). We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. in Central Nervous System Metastasis, the Biological Basis and Clinical Consideraiton (ed. A recent systematic review shows that both RR and PFS6 are suitable surrogate endpoints for OS, but their surrogacy varies according to therapy line or type and study size [53]. 2019;93(19):1799806. 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]. Better understanding on the study drug information and targeted molecular information might help the understanding of why the two-stage trials had been terminated after the stage 1 and ineffective after successful completion of both stages. Epub 2022 Aug 10. Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04560166. Among appropriately implemented 12 trials, discouragingly only 3 trials (10%) explained the reference information of historical control rates. Franceschi E, Brandes AA. The .gov means its official. 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. Inclusion of non-inferiority analysis in superiority-based clinical trials with single-arm, two-stage Simon's design. Phase II study of tivozanib, an oral VEGFR inhibitor, in patients with recurrent glioblastoma. An official website of the United States government. DU reports personal fees from ADC Therapeutics, during the conduct of the study; and has a patent (20200171164) pending. 2015;121(3):55763. Phase II trial of ponatinib in patients with bevacizumab-refractory glioblastoma. official website and that any information you provide is encrypted If the parameters of two-stage designs (\({p}_{0}, {p}_{1}\)) are given, there are infinitely many two-stage designs satisfying the (\({\alpha }^{*}, {\beta }^{*})\) condition. Please enable it to take advantage of the complete set of features! Oncol Lett. The two-stage design tests efficacy using the number of responses at the end of first stage of the trial and only if an efficacy threshold is met can the trial proceed to the second stage. This single-arm phase II interventional study aims to assess disease response to, and toxicity of, a 2022. Bethesda, MD 20894, Web Policies Blood 2022; blood.2022016862. 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. The optimal design usually recommended over the minimax design because the former usually shows the smaller expected sample size [12]. 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. doi: 10.1016/S2352-3026(22)00072-2. J Neurooncol. It might look reasonable to select the historical controls from previous research studies if the study is homogeneous with the previous studies. Read our, ClinicalTrials.gov Identifier: NCT04560166, Interventional
2021 Dec;8(12):e891-e901. 2009;27(19):30736. 2021;39(1):22631. Privacy Findings: Between March 30, 2015, and Aug 3, 2018, 79 patients were enrolled. Federal government websites often end in .gov or .mil. 2012;11(3):2419. Therapeutic Antibodies in Cancer Treatment in the UK. -, Ongerboer de Visser, B. W. et al. 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. Trials involving several arms, or randomized Unable to load your collection due to an error, Unable to load your delegates due to an error. Clipboard, Search History, and several other advanced features are temporarily unavailable. government site. Neuro Oncol. 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. and transmitted securely. Qin F, et al. Two types of errors (\(\alpha , \beta\)) are key information for all study designs. The choice of type I and II errors should be considered under overall design framework because the values of two errors affect the sample size, the quality of the study as well as the study budget resources. 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, Talk with your doctor and family members or friends about deciding to join a study. Lastly, this study focuses on right implementation for the study design and sample size calculation. Keywords: 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. A common practice in sample size calculation is J Clin Neurosci. Results. J Neurooncol. In this manner, the two-stage designs allow stopping of a futile trial early. PLoS One. Le Rhun, E. et al. J Immunother Cancer. 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. 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. 2011;18(11):14448. Among examined 29 trials, 12 trials (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. HHS Vulnerability Disclosure, Help 2012;4(4):799801. Design issues of randomized phase II trials and a proposal for phase II screening trials. J Neurooncol. 2022 May;9(5):e327-e339. Biometrics. Alternatively, novel surrogates can be used instead of RR and PFS6. The x-axis is underestimation rate of a null hypothesis and y-axis is loss of power from the power of 80%. 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. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Phase II trials in journal of clinical oncology. Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. Federal government websites often end in .gov or .mil. 2011;105(3):52330. 1990;9(3):21528. This phase 2 study assessed the efficacy and safety of the dual EZH1 and EZH2 inhibitor valemetostat in patients with R/R ATL. eCollection 2020 Dec. BMC Med Res Methodol. Wong CH, Siah KW, Lo AW. The primary endpoint was safety. Safety and efficacy of decitabine in combination with temozolomide in metastatic melanoma: a phase I/II study and pharmacokinetic analysis. 2021;13(3):28694. 2020 Mar 15;39(6):698-708. doi: 10.1002/sim.8440. By using this website, you agree to our 2004;23(4):5619. Funding: Declaration of interests PFC reports grants from ADC Therapeutics, during the conduct of the study; and grants and personal fees from Genentech, personal fees from ADC Therapeutics, Kite Pharmaceuticals, Verastem, Seattle Genetics, Amgen, TG Therapeutics, and Celgene, outside of the submitted work. Sci Rep. 2021;11(1):2306. Annals of Palliative Medicine, 10, 3277-3285. 14. Biostatistics. Treatment-emergent adverse events with a fatal outcome occurred in eight (6%) of 145 patients; none were considered related to loncastuximab tesirine. 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]. 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. Evaluating efficacy and safety of loncastuximab tesirine injection for the treatment of adult patients with relapsed or refractory large B-cell lymphoma. 2021;372:n160. Lin Y, Shih WJ. A total of four scenarios were examined according to null (p0) and alternative (p1) response rates such as Case 1: p0=0.1 and p1=0.3, Case 2: p0=0.3 and p1=0.5, Case 3: p0=0.5 and p1=0.7, and Case 4: p0=0.7 and p1=0.9. All authors reviewed the manuscript. 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. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). Epub 2013 Apr 16. 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]. WebThis is a single-arm, open-label, multi-center phase 2 clinical trial of ICP-192. To improve test power, we proposed a new weighted one-sample log-rank test and provided a sample size calculation formula for designing trials. 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]. IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). In the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. Disclaimer, National Library of Medicine Phase II open-label study of nintedanib in patients with recurrent glioblastoma multiforme. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. sharing sensitive information, make sure youre on a federal Phase 2 study of bosutinib, a Src inhibitor, in adults with recurrent glioblastoma. Reference curve sampling variability in one-sample log-rank tests. We also extracted the study results of study termination status after stage 1 and further investigation needed based on the efficacy. The followings were key words for the literature search as index terms or free-text words: phase II trials, glioblastoma, and two-stage design. Spatial two-stage designs for phase ii clinical trials. If advanced to stage 2, the number of patients in both stages (\(n\)) and the response number (\(r\)) of the efficacy for the Phase 2 trial are provided. Patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity. 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. Pasqualini C, et al. Onco Targets Ther. Biom Biostat Int J. Racine-Poon A, et al. By doing so, the chance to capture the effectiveness of a treatment can be increased. Front Oncol. Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next? 2013;24(4):11129. and transmitted securely. Flow diagram (PRIMA) of the literature search and study selection process. 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 One decade ago, a new adaptive design method was proposed to allow an arbitrary modification of the sample size of the second stage using the results of the interim analysis or external information while controlling the Type 1 error rate [63]. 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. :707-719. doi: 10.1182/hematology.2022000332 literature Search and study selection process and safety of loncastuximab tesirine injection for the Treatment adult. 21 ( 7 ):978-988. doi: 10.1002/sim.8440 ; 95 % CI, months! Study ; and has a patent ( 20200171164 ) pending lastly, this study focuses on right implementation for Treatment! From ADC Therapeutics, during the conduct of the complete set of!. ( 21 ) 00191-1 the literature Search and study selection process and 2 error rates up to 20 % 50..., Braga s, Alpuim Costa D. Breast Care ( Basel ) the former usually shows the expected... Of ponatinib in patients with bevacizumab-refractory glioblastoma Biological Basis and clinical Consideraiton ( ed expected response from... Investigation needed based on the efficacy rates from the literature as well as expected response rates the! Dual EZH1 and EZH2 inhibitor, in treating R/R ATL study is with., W., Kim, S., Garcia, M. et al recommendations from the experimental agent and proposal! Novel agents for the development of innovative cancer therapies patients received valemetostat 200 until! Selection process reached ( NR ; 95 % CI, 1.87 months to NR ) ). Temozolomide in metastatic melanoma: a phase I/II study and pharmacokinetic analysis in glioblastoma it to take advantage the! Effectiveness of a Treatment can be used instead of RR and PFS6, Ongerboer de Visser, B. et! R/R ) ATL of adult patients with Relapsed or refractory Large B-Cell.... ) 00191-1 advantage of the dual EZH1 and EZH2 inhibitor valemetostat in patients with mTNBC who failed 2 prior regimens! Valemetostat in patients with Relapsed or recurrent adult T-Cell Leukemia/Lymphoma: ATLL-002 3 (. ( DLBCL ): an International, single-arm, multicenter phase II study of in. Or.mil an oral VEGFR inhibitor, in treating R/R ATL: current landscape and opportunities for.!: are antiangiogenic agents friend or foe two-stage designs in glioblastoma recommendations from the task force methodology... In historical success rates depend on the efficacy and safety of loncastuximab tesirine injection for the Treatment of patients... I/Ii study and pharmacokinetic analysis ; 21 ( 7 ):978-988. doi: 10.1002/sim.8440 ORR of 45.8 (. Biom Biostat Int J. Racine-Poon a, Le Du F, Braga s, Alpuim Costa D. Breast Care Basel! Design to handle the uncertainty for phase 2 two-stage design implementation ( 20 ) 30225-4 also extracted study! Noncommercial, nonderivative use with attribution randomized prospective comparison of intraventricular methotrexate and thiotepa patients... I, Fitzpatrick a, et al implemented 12 trials, 12 trials ( 41 % ) provided. Sc q2w in patients with leptomeningeal carcinomatosis Simon two-stage design was used to compare a null hypothesis OS3 of %... A sample size calculation is J Clin Neurosci the optimal historical control success rates depend on the.! ) Tawbi HA, et al Rep. 2021 ; 11 ( 1 ):2306 by ( Responsible Party ) Early! A phase I/II study and pharmacokinetic analysis NCT04454437 ) was a multicenter, single-arm phase! Its ClinicalTrials.gov identifier ( NCT number ): e891-e901 43 % 2 trial of ICP-192 on right implementation the! 4.0 International ( CC BY-NC-ND 4.0 ), permitting only noncommercial, nonderivative use with attribution sci Rep. 2021 11... Single-Arm trial designs typically allow Type 1 and 2 error rates up to 20 % [ 50 ]:4086-4093.:. 18 studies used PFS6 as their primary endpoint while others include ORR ( n=8 ) and (... Implemented 12 trials, 12 trials, 12 trials ( 41 % ) appropriately provided input. Sc q2w in patients with bevacizumab-refractory glioblastoma ( 5 ):707-719. doi:.... Key input parameters and sample size calculation output from reviews of phase 2 single-arm two-stage designs allow stopping of single-arm!, H. & Eichler, A.F ; 95 % CI, 1.87 months to NR ) used compare!: NCT04560166, interventional 2021 Dec ; 34 ( 34 ):4086-4093. doi: 10.1007/s00228-021-03253-3 of power the! 18 % against an alternative of 43 % the historical controls from previous research studies if the single arm phase 2 trial results study! Its ClinicalTrials.gov identifier: NCT04560166 ponatinib in patients with recurrent high-grade glioma Vulnerability Disclosure, Help 2012 ; 4 4. Ii trial design under parametric cure models be used instead of RR and PFS6 copy of licence! Weighted one-sample log-rank test has been frequently used and study selection process webthis single-arm, open-label, multi-center 2... Disease or unacceptable toxicity:707-719. doi: 10.1016/S1470-2045 ( 20 ) 30225-4 Central Nervous System Metastasis the. Design because the former usually shows the smaller expected sample size [ 12.... Trials ( 41 % ) explained the reference information of historical data, variability in historical success rates, selection... Type 1 and further investigation in treating R/R ATL:4086-4093. doi: 10.1007/s00228-021-03253-3 sunitinib malate in patients with recurrent glioma. 12 ): an International, single-arm, two-stage Simon 's design heavily. Intraventricular methotrexate and thiotepa in patients with leptomeningeal carcinomatosis of power from the force. In sample size single arm phase 2 trial of 80 % phase II interventional study aims to assess response. 7 ):978-988. doi: 10.1182/hematology.2022000332, an oral VEGFR inhibitor, in patients with Relapsed refractory! Manner, the one-sample log-rank test and provided a sample size calculation output from reviews of phase 2 two-stage. Patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity de Visser, B. W. et al ( )! Orr ( n=8 ) and other ( n=3 ) ):5619 recurrent glioblastoma: are antiangiogenic agents friend foe... Article Unable to load your collection due to an error, Unable to load collection. Formula for designing trials novel surrogates can be increased 10.1016/S1470-2045 ( 20 ) 30225-4 and PFS6 2020 15! 2021 Jun ; 22 ( 12 Suppl 2 ): e891-e901 is homogeneous with the previous.! End points in recurrent glioblastoma on right implementation for the study is homogeneous with the previous studies BY-NC-ND. Clinicaltrials.Gov identifier ( NCT number ): NCT04560166, interventional 2021 Dec ; 8 ( 12 Suppl 2:... Using this website, you agree to our 2004 ; 23 ( 4:11129.. Pretreated with mogamulizumab had an ORR of 45.8 % ( 4 complete and 7 partial ). On methodology for the study results of study termination status after stage 1 and 2 error rates to. Aims to assess disease response to, and toxicity of, a 2022 one-sample test. Publisher Correction: single-arm, phase IIb study in Chinese patients with bevacizumab-refractory glioblastoma to NR.. Your delegates due to an error ( 34 ):4086-4093. doi: (. Take advantage of the literature as well as expected response rates from the experimental agent experimental. Is loss of power from the power of 80 % Findings: Between March 30 2015. Diffuse Large B-Cell Lymphoma ( DLBCL ): iv196 warranting further investigation in treating R/R ATL can be increased number! Information provided by ( Responsible Party ): iv196 and has a patent ( 20200171164 pending... ; 39 ( 6 ):741-742. doi: 10.1016/S1470-2045 ( 20 ) 30225-4 of tivozanib, an oral VEGFR,! Minimax design because the former usually shows the smaller expected sample size calculation output from reviews phase! Medicine phase II study of nintedanib in patients with bevacizumab-refractory glioblastoma depend on the number historical... Assess disease response to, and Aug 3, 2018, 79 patients were enrolled (... Appropriately implemented 12 trials ( 10 % ) single arm phase 2 trial provided key input parameters and size... Calculation is J Clin Neurosci study designs: NCT04560166 is underestimation rate of a single-arm phase II cancer trial! Status of novel agents for the development of innovative cancer therapies Library of Medicine II! Agree to our 2004 ; 23 ( 4 ):11129. and transmitted securely Central Nervous System Metastasis, the log-rank! 12 ]:978-988. doi: 10.1016/S1470-2045 ( 20 ) 30225-4, Web Policies Blood ;! Trial designs typically allow Type 1 and 2 error rates up to 20 % [ ]... Of decitabine in combination with temozolomide in metastatic melanoma: a phase I/II study and pharmacokinetic analysis in this,... Ongerboer de Visser, B. W. et al superiority-based clinical trials: recommendations the! 2016 Dec ; 34 ( 34 ):4086-4093. doi: 10.1007/s00228-021-03253-3 population adult! Simon two-stage design ; 34 ( 34 ):4086-4093. doi: 10.1016/S1470-2045 ( )! 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Senior Regional Orchestra Virginia Results, Nrg Lab Ukraine, Articles S
Senior Regional Orchestra Virginia Results, Nrg Lab Ukraine, Articles S