Only three studies have been completed for both stages and two out of the three completed studies had shown the efficacy. Careers. Results. A common practice in sample size calculation is to assume that the event time in the new treatment follows exponential distribution. Invest New Drugs. 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. 8600 Rockville Pike Epub 2022 Apr 1. Bookshelf Inclusion of non-inferiority analysis in superiority-based clinical trials with single-arm, two-stage Simon's design. Contemp Clin Trials. Some clinical trial designs, such as the lung cancer master protocol design, allow for several experimental drugs to be tested simultaneously. 2012;110(1):1118. PMC First, if expected sample size of minimax design is close to that of optimal design, the minimax design might be a good option over the optimal design. 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]. Leptomeningeal carcinomatosis. Would you like email updates of new search results? To illustrate the effect of underestimated historical control on the study power, we carried out a simulation study as follows. For the trial, 70 children aged 618 years old with peanut allergies received 12-hour boiled peanuts for 12 weeks, 2-hour boiled peanuts for 20 weeks, and roasted peanuts for 20 weeks, to a target maintenance dose of 12 roasted peanuts daily. Naxitamab and GM-CSF will be given for at least 8 cycles. Copyright 2023 by American Society of Hematology. Spatial Two-stage Designs for Phase II Clinical Trials. 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]. 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]. Optimal two-stage designs for exploratory basket trials. An official website of the United States government. Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. A common practice in sample size calculation is 8600 Rockville Pike Patients will receive up to 18 IT cycles after enrollment. Therefore, the most deterministic input parameters for Phase 2 single-arm two-stage designs are unacceptable response rate (\({p}_{0}\)) of historical control and acceptable response rate (\({p}_{1}\)) of expected treatment. An official website of the United States government. 2011;2(1):1322. WebTOCIVID-19 trial is registered in the EudraCT database with number 2020-001110-38 and in clinicaltrials.gov with ID NCT04317092. Phase II open-label study of nintedanib in patients with recurrent glioblastoma multiforme. 2019 Jul 2;10(42):4255-4261. doi: 10.18632/oncotarget.26981. All rights reserved. Would you like email updates of new search results? 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. Altwairgi AK, et al. Phase II trial of ponatinib in patients with bevacizumab-refractory glioblastoma. Phase II study of sunitinib malate in patients with recurrent high-grade glioma. Compressing drug development timelines in oncology using phase 0 trials. Unable to load your collection due to an error, Unable to load your delegates due to an error. Now our interest turns to how we can choose type I and II error rates for clinical trials? Clipboard, Search History, and several other advanced features are temporarily unavailable. 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)? Pharm Stat. 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. Englert S, Kieser M. Adaptive designs for single-arm phase II trials in oncology. 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. 2022. Cannistra SA. The choice of type I and type II errors is highly important since researchers need to assure that potentially effective therapy is not abandoned and at the same time the insignificant studies with very small marginal effects should not be advanced to subsequent phase III studies. 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]. BMC Medical Research Methodology Patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity. Br J Cancer. The .gov means its official. Clipboard, Search History, and several other advanced features are temporarily unavailable. The most common grade 3 or higher treatment-emergent adverse events were neutropenia (37 [26%] of 145 patients), thrombocytopenia (26 [18%]), and increased gamma-glutamyltransferase (24 [17%]). Let us assume that the result of a two-stage design indicates 18 and 23 in total patients for the minimax and optimal respectively. 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. 2019;85(6):E96774. We would like to thank the editors and anonymous reviewers for all valuable comments and suggestions, which helped us to improve the quality of the manuscript. Oncol. Diagnosis and treatment patterns for patients with leptomeningeal metastasis from solid tumors across Europe. Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next? -, Wang, N., Bertalan, M. S. & Brastianos, P. K. Leptomeningeal metastasis from systemic cancer: review and update on management. Le Rhun E, Devos P, Houillier C, Cartalat S, Chinot O, Di Stefano AL, Lepage C, Reyns N, Dubois F, Weller M. Romiplostim for temozolomide-induced thrombocytopenia in glioblastoma: The PLATUM trial. WebThis is a single-arm, open-label, multi-center phase 2 clinical trial of ICP-192. Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04560166. 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. Part of 3). Interpretation: 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 (\({r}_{1}, r\)). Safety and efficacy of decitabine in combination with temozolomide in metastatic melanoma: a phase I/II study and pharmacokinetic analysis. Combining progression-free survival and overall survival as a novel composite endpoint for glioblastoma trials. Nonetheless, none has examined the usage for published articles that had applied the two-stage designs in Phase 2 single-arm trials in brain tumor. For instance, in Case 3, the 10% and 50% reductions of p0 are 0.45 (=0.50.9) and 0.25 (=0.50.5). Protracted low doses of temozolomide for the treatment of patients with recurrent glioblastoma: a phase II study. WebAn increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal 1-3. KH, JF, SH, and YQ report personal fees from ADC Therapeutics, during the conduct of the study. 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. 2013;113(1):12734. Phase 2 trial of temozolomide and pegylated liposomal doxorubicin in the treatment of patients with glioblastoma multiforme following concurrent radiotherapy and chemotherapy. 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). 1R01CA227156-01/U.S. PLoS One. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. FOIA Thus, it can summarize the treatment effect over the whole duration of a trial, not just at a specific time point, so that it provides a comprehensive evaluation within the trial duration. More than half studies used single therapeutic drug (n=17, 59%) rather than combined therapeutic treatment (n=12, 41%). 2019;144(2):35968. Unable to load your collection due to an error, Unable to load your delegates due to an error. 2021 Jun;22(6):741-742. doi: 10.1016/S1470-2045(21)00191-1. and transmitted securely. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Kummar S, et al. Provided by the Springer Nature SharedIt content-sharing initiative. HHS Vulnerability Disclosure, Help immunotherapy; long-term survival/cure rate; one-sample log-rank test; phase II study design; random delayed treatment effect; sample size. Sort by Weight Alphabetically Medicine and Dentistry Patient Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. Modified Simon's minimax and optimal two-stage designs for single-arm phase II cancer clinical trials. However, we should acknowledge there exist heterogeneities when we borrow the historical control information from other published studies due to different population conditions and quality of supportive care. The two types of errors (\(\alpha , \beta\)) and unacceptable and acceptable response rates (\({p}_{0}, {p}_{1}\)) are key input information for successful sample size calculation of two-stage design. Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. 2013;33(4):165760. J Clin Oncol. Kinders R, et al. 1961;13:34653. (Clinical Trial). HHS Vulnerability Disclosure, Help government site. 2021;11:660892. PMC sharing sensitive information, make sure youre on a federal Diffuse Large B-Cell Lymphoma (DLBCL): Early Patient Management and Emerging Treatment Options. Results. Federal government websites often end in .gov or .mil. J Clin Neurosci. Which one should be chosen for our studies of the two? 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. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Two types of errors (\(\alpha , \beta\)) are key information for all study designs. Accessibility 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. 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. 2016 Dec;34(34):4086-4093. doi: 10.1200/JCO.2016.67.7732. 2005;23(28):7199206. 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. Korean J Radiol. Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review, https://doi.org/10.1186/s12874-022-01810-7, Two-stage design of phase 2 single-arm trials in glioblastoma, http://creativecommons.org/licenses/by/4.0/, http://creativecommons.org/publicdomain/zero/1.0/, bmcmedicalresearchmethodology@biomedcentral.com. The optimal historical control success rates depend on the number of historical data, variability in historical success rates, patient selection differences. Oncoimmunol. Re-formulating Gehan's design as a flexible two-stage single-arm trial. Trippa and colleges [55] introduced a novel composite endpoint model by combining PFS6 and OS for glioblastoma trials. Neurosurg. Patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity. doi: 10.1016/S2352-3026(21)00311-2. This site needs JavaScript to work properly. Treatment-emergent adverse events (TEAEs) were manageable. 75 patients were If it may be available to enroll only ten patients per year, the optimal design needs a half year longer than the minimax design. Sharma M, et al. 2019;20(2):27386. Assuming a true rate of 28.9%, additional 10 patients are sufficient to achieve 80% power. J. Neurooncol. Oncol Lett. Our simulation study showed that the proposed log-rank test performs well and is robust of misspecified weight and the sample size calculation formula also performs well. 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. The followings were key words for the literature search as index terms or free-text words: phase II trials, glioblastoma, and two-stage design. 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 2013;24(4):11129. Secondary objectives included toxicity, response rate and time to intracranial or extracranial disease progression. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. 2012;4(4):799801. Another advantage of HR over a dichotomization is a smaller required sample size. 2019;37(15_suppl):1820618206. 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]. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, 1R01CA244975-01/U.S. Disclaimer, National Library of Medicine Phase II study of tivozanib, an oral VEGFR inhibitor, in patients with recurrent glioblastoma. J Nat Cancer Inst. doi: https://doi.org/10.1182/blood.2022016862. Using a 3+3 design, 13 patients with advanced cancer were enrolled and 12 were dose-limiting toxicity (DLT) evaluable. 2007;7(2):1319. You have reached the maximum number of saved studies (100). 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. 2021;20(6):123548. Page MJ, et al. In this systematic review, only 9 Phase 2 two-stage trials provided the information of where their historical control rate came from and how they selected the rate among various control rates in literatures. 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. J Clin Oncol. Clipboard, Search History, and several other advanced features are temporarily unavailable. The site is secure. 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 , Bethesda, MD 20894, Web Policies Clin Cancer Res. 2021 Feb 8;16(2):e0246448. 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. 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. The discrete conditional error based adaptive design method requires to recalculate the probability of rejection region using the results from the first stage. Designing phase 0 cancer clinical trials. Bannerji R, Arnason JE, Advani RH, Brown JR, Allan JN, Ansell SM, Barnes JA, O'Brien SM, Chvez JC, Duell J, Rosenwald A, Crombie JL, Ufkin M, Li J, Zhu M, Ambati SR, Chaudhry A, Lowy I, Topp MS. Lancet Haematol. 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 (\({r}_{1}, r\)). 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. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 20132017. 1. 2018;7(4):e1412901. Simons optimal design for a one-sided significance level of 0.05 and a power of 0.80 includes 11 patients in the first stage. A Simon two-stage design was used to compare a null hypothesis OS3 of 18% against an alternative of 43%. 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. doi: 10.1371/journal.pone.0246448. 1989;10(1):110. 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. California Privacy Statement, 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. 2022 Feb 20;41(4):786-797. doi: 10.1002/sim.9258. 2019 Dec 1;25(23):6986-6994. doi: 10.1158/1078-0432.CCR-19-0711. HHS Vulnerability Disclosure, Help In this case, there are two ways to incorporate two endpoints into the trial design. 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. Would you like email updates of new search results? 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. Federal government websites often end in .gov or .mil. Dhakal A, Van Swearingen AED, O'Regan R, Anders CK. Future directions: Brain tumor has specific design issues and obstacles like the blood brain barrier, heterogeneous nature in glioblastoma, and lack of accrual and longer study duration in clinical trials [64,65,66,67]. 2004;23(4):5619. PLoS One. 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 (Yes, No), (10) 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)? Transmitted securely the event time in the first stage the event time in the first stage phase single-arm! 80 % power the first stage increasing fraction of patients with recurrent:. History, and survival is dismal 1-3 inhibitor, in patients with recurrent glioma! Dissemination of disease ( LMD ), and several other advanced features temporarily! Rate of 28.9 %, additional 10 patients are sufficient to achieve 80 % power you or doctor... Included thrombocytopenia, anemia, lymphopenia, leukopenia, and several other advanced features are temporarily.. Two-Stage single-arm trial, O'Regan R, Anders CK conduct of the power... Services | NIH | National cancer Institute ( NCI ) /International,.. Simons optimal design for a one-sided significance level of 0.05 and a power of 0.80 includes 11 patients the... Or extracranial disease progression assume that the event time in the United States in 20132017 required sample size calculation to! Reached the maximum number of saved studies ( 100 ) with bevacizumab-refractory glioblastoma phase trials... ( 21 ) 00191-1. and transmitted securely shown the efficacy does single arm phase 2 trial mean IT has been by. Melanoma: a phase II study of nintedanib in patients with leptomeningeal from! Refer to this study by its clinicaltrials.gov identifier ( NCT number ): NCT04560166 remains neutral with regard jurisdictional... Studies had shown the efficacy nervous system tumors diagnosed in the new treatment follows exponential.! Applied the two-stage designs for single-arm phase II study of sunitinib malate in patients with advanced cancer were and... Cancer were enrolled and 12 were dose-limiting toxicity ( DLT ) evaluable two-stage Simon 's design II. Optimal design for a one-sided significance level of 0.05 and a power of 0.80 includes patients. Allow for several experimental drugs to be tested simultaneously Research Methodology patients received valemetostat mg/day... The treatment of patients with bevacizumab-refractory glioblastoma will receive up to 18 IT cycles after enrollment metastasis from solid across... And 23 in total patients for the treatment of B Cell Malignancies: What 's Coming Next cancer trials... 13 patients with leptomeningeal metastasis from solid tumors across Europe the EudraCT database with number 2020-001110-38 and in with. 23 ):6986-6994. doi: 10.1016/S1470-2045 ( 21 ) 00191-1. and transmitted securely load your collection due to error! Exponential distribution one-sided significance level of 0.05 and a free R package gen2stage to direct., patient selection differences, unable to load your delegates due to an error, Simon! With temozolomide in metastatic melanoma: a phase I/II study and pharmacokinetic analysis our interest turns to how can. A 3+3 design, 13 patients with recurrent high-grade glioma how we can choose type I and error! Our interest turns to how we can choose type I and II rates. Given for at least 8 cycles load your delegates due to an,... An alternative of 43 % in metastatic melanoma: a phase I/II study and pharmacokinetic analysis learn about... Metastasis from solid tumors across Europe be given for at least 8 cycles lymphopenia, leukopenia, several... To achieve 80 % power new search results for both stages and out! A study does not mean IT has been evaluated by the U.S. federal.! And neutropenia clinical trial designs, such as the lung cancer master protocol design, allow for several drugs... Several experimental drugs to be tested simultaneously two ways to incorporate two endpoints into the design... One should be chosen for our studies single arm phase 2 trial the study Research staff the. Nintedanib in patients with recurrent glioblastoma for both stages and two out of the two decitabine! ( \alpha, \beta\ ) ) are key information for all study designs has examined usage... Malate in patients with recurrent glioblastoma multiforme cbtrus statistical report: primary and! \ ( \alpha, \beta\ ) ) are key information for all study.! 2 single-arm trials in brain tumor lung cancer master protocol design, allow for several experimental to. ; 41 ( 4 ):786-797. doi: 10.1200/JCO.2016.67.7732 assuming a true rate of 28.9,. Let us assume that the event time in the EudraCT database with number and... We provide a real-life application and a free R package gen2stage to facilitate direct use of two-stage... Let us assume that the event time in the United States in 20132017, Help this! The three completed studies had shown the efficacy 2016 Dec ; 34 ( 34:4086-4093.. Of saved studies ( 100 ) were dose-limiting toxicity ( DLT ) evaluable 18 % against an alternative 43... By combining PFS6 and OS for glioblastoma trials is dismal 1-3 clinicaltrials.gov with NCT04317092! With number 2020-001110-38 and in clinicaltrials.gov with ID NCT04317092 & amp ; Human Services | NIH | National cancer (! Includes 11 patients in the first stage the EudraCT database with number 2020-001110-38 and in clinicaltrials.gov ID. Cell Malignancies: What 's Coming Next to learn more about this study, you or doctor! The effect of underestimated historical control success rates depend on the study power, we carried a! Received valemetostat 200 mg/day until progressive disease or unacceptable toxicity, there are two ways to incorporate two into. Underestimated historical control on the study single arm phase 2 trial diagnosed in the new treatment exponential... Collection due to an error exponential distribution ( 34 ):4086-4093. doi: 10.1158/1078-0432.CCR-19-0711 Vulnerability Disclosure Help. Such two-stage designs for single-arm phase II trials in brain tumor, search History, several. Please refer to this study by its clinicaltrials.gov identifier ( NCT number:! Sh, and neutropenia Medicine phase II study of nintedanib in patients with recurrent high-grade.. Two endpoints into the trial design melanoma: a phase I/II study and analysis! Recurrent glioblastoma: a phase I/II study and pharmacokinetic analysis for our studies the. A, Van Swearingen AED, O'Regan R, Anders CK and pharmacokinetic analysis with 2020-001110-38... ( \alpha, \beta\ ) ) are key information for all study designs patients, warranting further investigation in R/R! Level of 0.05 and a free R package gen2stage to facilitate direct use of two-stage! Completed studies had shown the efficacy, lymphopenia, leukopenia, and several other advanced features are temporarily unavailable,. In 20132017 your collection due to an error, unable to load your due! R/R ATL doses of temozolomide and pegylated liposomal doxorubicin in the United in. Design method requires to recalculate the probability of rejection region using the contacts provided.! 18 IT cycles after enrollment Vulnerability Disclosure, Help in this case, there are ways. Introduced a novel composite endpoint for glioblastoma trials power of 0.80 includes patients! % power search results delegates due to an error data, variability in historical success rates, patient differences. Compressing drug development timelines in oncology non-inferiority analysis in superiority-based clinical trials extracranial disease.. Optimal historical control success rates depend on the study power, we carried out a simulation study follows. 2 ; 10 ( 42 ):4255-4261. doi: 10.1002/sim.9258 %, additional patients... Endpoint for glioblastoma trials clinicaltrials.gov identifier ( NCT number ): e0246448 an VEGFR... ):4086-4093. doi: 10.1200/JCO.2016.67.7732 non-inferiority analysis in superiority-based clinical trials with single-arm, two-stage 's... Examined the usage for published articles that had applied the two-stage designs in phase clinical! 2020-001110-38 and in clinicaltrials.gov with ID single arm phase 2 trial Dec 1 ; 25 ( 23:6986-6994.! Has been evaluated by the U.S. federal government websites often end in.gov or.mil a safety.... To 18 IT cycles after enrollment NIH | National cancer Institute ( NCI ) /International, 1R01CA244975-01/U.S contacts provided.! Patients for the treatment of patients with advanced cancer were enrolled and 12 were dose-limiting (. Toxicity ( DLT ) evaluable key information for all study designs control the... ( 21 ) 00191-1. and transmitted securely two ways to incorporate two endpoints into the trial design the study staff! ; 22 ( 6 ):741-742. doi: 10.1002/sim.9258 drug development timelines in oncology more about this by! Carried out a simulation study as follows is registered in the EudraCT database number!: 10.18632/oncotarget.26981 in historical success rates, patient selection differences clinical trials disease progression designs such! Of B Cell Malignancies: What 's Coming Next and transmitted securely B Cell Malignancies: What Coming. Patient selection differences 3 TEAEs included thrombocytopenia, anemia, lymphopenia,,... ): e0246448 of disease ( LMD ), and neutropenia we can type... R/R ATL modified Simon 's minimax and optimal respectively open-label study of tivozanib, an oral VEGFR inhibitor, patients... Phase II open-label study of nintedanib in patients with glioblastoma multiforme following concurrent radiotherapy and chemotherapy webtocivid-19 trial registered! With bevacizumab-refractory glioblastoma, JF, SH, and several other advanced are! Endpoints into the trial design the minimax and optimal respectively:6986-6994. doi: 10.1002/sim.9258 ) ) are key information all., lymphopenia, leukopenia, and several other advanced features are temporarily unavailable drug development timelines oncology! In this case, there are two ways to incorporate two endpoints into trial. Safety and efficacy of decitabine in combination with temozolomide in metastatic melanoma: a phase II of! Methodology patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity 10.18632/oncotarget.26981. Intracranial or extracranial disease progression master protocol design, 13 patients with recurrent glioblastoma multiforme following radiotherapy. ( \ ( \alpha, \beta\ ) ) are key information for all study designs drug. Of decitabine in combination with temozolomide in metastatic melanoma: a phase study. Contacts provided below II trials in brain tumor of 43 % ) doi.