WebIn the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. 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. Another option of two-stage designs is admissible design or spatial design, which came from an idea Can we find a good alternative design between the minimax and optimal design. 2022 Nov 23;23(23):14589. doi: 10.3390/ijms232314589. Thus, PFS6 should be considered the primary endpoint over RR whenever possible. Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review. Perspect Clin Res. 2022 Dec;17(6):524-532. doi: 10.1159/000526431. 2023 Jan;37(1):45-67. doi: 10.1007/s40263-022-00975-5. Article 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. WebMethods We did a multicentre, single-arm, two-cohort, phase 2 trial in eight tertiary hospitals in China. Bagley SJ, et al. Their composite endpoint model provides efficiency while still maintaining the clinical relevance of OS. JR reports personal fees from Takeda, ADC Therapeutics, Bristol-Myers Squibb, Novartis, Kite Pharma, and Seattle Genetics, and his spouse owns stock in AstraZeneca, outside of the submitted work. doi: https://doi.org/10.1182/blood.2022016862. 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. 2019;8(13):598894. Neuro Oncol. An armof a clinical trial is a group of patients receiving a specific treatment (or no treatment). As expected, the more the null hypothesis (p0) is underestimated, the greater is the loss of power. Kalpathy-Cramer J, et al. official website and that any information you provide is encrypted The Phase 2 trials often apply single-arm study designs to identify the efficacious treatment by using historical control data for comparative evaluation with study treatment data. Thank you for submitting a comment on this article. 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. Cancer immunotherapy trial design with random delayed treatment effect and cure rate. A treatment cycle is 21 days. 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. Breslow NE. Thall PF, Simon R. Incorporating historical control data in planning phase II clinical trials. Detailed Description: This is an international, single-arm, multicenter phase 2 trial, in Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. We show that Simon's two-stage designs for efficacy studies can be similarly used to design a two-stage safety study by modifying some of the design parameters. 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. government site. HHS Vulnerability Disclosure, Help End of study was approximately 8 1 weeks (57 7 days) after the first drug administration. Expert Rev Anticancer Ther. WebMethods: We did a multicentre (28 hospital sites in the USA, UK, Italy, and Switzerland), open-label, single-arm, phase 2 trial (LOTIS-2) in patients aged 18 years or older with 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. Mateos et al. For general information, Learn About Clinical Studies. Patients will receive naxitamab + GM-CSF + irinotecan/temozolomide. 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 Only three studies have been completed for both stages and two out of the three completed studies had shown the efficacy. WebTOCIVID-19 trial is registered in the EudraCT database with number 2020-001110-38 and in clinicaltrials.gov with ID NCT04317092. 1982;38(1):14351. Experimental arms, which receive an experimental drug, are compared with control arms, which can receive an active comparator (another therapy used to treat the same condition as the experimental therapy), a placebo comparator (an inactive therapy), a sham comparator (an inactive therapy made to look identical to the active therapy), or no intervention. 2019;85:105807. We conducted the prospective, open-label, single-arm, phase 2 TUXEDO-1 trial. Estimation of clinical trial success rates and related parameters. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Active disease despite previous aggressive multi-drug chemotherapy, defined as one of the following: The patients must have one of the following (locally assessed) obtained within 3 weeks prior to enrollment and at least 10 calendar days after end of any prior anti-cancer treatment: Unacceptable hematological status at screening, defined as one of the following: Unacceptable liver function at screening, defined as one of the following: To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. Geoerger B, et al. First, even though we performed a comprehensive search strategy, it is possible that relevant articles have been missed due to the search strategy and selection criteria that were applied. Polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed or refractory follicular lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study. Oncol Lett. 2020 Jul;21(7):978-988. doi: 10.1016/S1470-2045(20)30225-4. Figure1 shows flow diagram (PRIMA) of the literature search and study selection process. Phase II trial of an AKT inhibitor (perifosine) for recurrent glioblastoma. Ivy Brain Tumor Center, Department of Translational Neuroscience, Barrow Neurological Institute, Phoenix, AZ, 85013, USA, Karmanos Cancer Institute, Department of Oncology, School of Medicine, Wayne State University, Detroit, MI, 48201, USA, Department of Radiation Oncology, Barrow Neurological Institute, Phoenix, AZ, 85013, USA, You can also search for this author in All rights reserved. To illustrate the effect of underestimated historical control on the study power, we carried out a simulation study as follows. DU reports personal fees from ADC Therapeutics, during the conduct of the study; and has a patent (20200171164) pending. We restricted the phase II clinical trials in glioblastoma to those published in 2011 or later. Wouters OJ, McKee M, Luyten J. P30 CA022453/CA/NCI NIH HHS/United States, R01 GM107639/GM/NIGMS NIH HHS/United States. 2021;150:5362. 2008;14(12):367582. Childs Nerv Syst. Multistage designs for phase II clinical trials: statistical issues in cancer research. Pembrolizumab in Patients With Extensive-Stage Small-Cell Lung Cancer: Results From the Phase Ib KEYNOTE-028 Study. Nat Commun. Treatment-emergent adverse events (TEAEs) were manageable. Only three trials (11%) provided key input parameters, appropriately reported output results from sample size calculation of two-stage designs, and finally provided the reference and explanation of historical control rates. Particularly, a recent research of the phase 2 basket trials has extended the two-stage design for multiple heterogeneous indications, which is an important tool to identify the effective drug through a generalized framework of an optimal basket design. The .gov means its official. Epub 2020 Jun 5. Curr Treat Options Oncol. 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. Therapeutic Antibodies in Cancer Treatment in the UK. J Clin Oncol. 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. Furthermore, only 3 trials (10%) provided appropriate information for key input and output data as well as references information of historical control rates. 2015 May-Jun;14(3):226-32. doi: 10.1002/pst.1678. Before The .gov means its official. FOIA Designing phase 0 cancer clinical trials. Pellegatta S, et al. Clinical end points in recurrent glioblastoma: are antiangiogenic agents friend or foe? Taylor JW, et al. (Clinical Trial). Simon's two-stage designs are frequently used in phase II single-arm trials for efficacy studies. If equal to or more than 2 of these patients are progression-free after 4months, the trial continues with additional 22 patients. OPTIM-ARTSAn adaptive phase II open platform trial design with application to a metastatic melanoma study. 2013;10(5):72034. 133, 419427 (2017). Valemetostat 200 mg orally once Using We systematically reviewed published single-arm two-stage Phase 2 trials for patients with glioblastoma and high-grade gliomas (including newly diagnosed or recurrent). Lassman AB, et al. Cancer Med. Kummar S, et al. 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. Kieser M, Rauch G. Two-stage designs for cross-over bioequivalence trials. Kim S, Wong WK. Please check for further notifications by email. Most trials (n=22, 76%) successfully provided all key information while 7 trials (24%) failed to provide at least one key information (Six trials failed to provide two types of error rates, four trials failed to provide two response rates, and three trials failed to provide two or more than two key results from the sample size calculation). FOIA Twenty patients-17 with breast cancer, two with lung cancer and one with ovarian cancer-were enrolled into the pre-specified evaluation group having received at least one dose of pembrolizumab. Read our, ClinicalTrials.gov Identifier: NCT04560166, Interventional 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. Unable to load your collection due to an error, Unable to load your delegates due to an error. In summary, Simons 2-stage designs, under the same type 1 error rate and power, the minimax design has a smaller total sample size than the optimal design, while the optimal design has a smaller stage 1s sample size than the minimax design. Google Scholar. Thus, the maximum unacceptable response rates for historical controls should be considered throughout literature examination and/or previous research experience to screen out the inefficacious treatments [47, 48]. Simons two-stage designs have been widely used for single-arm trials in glioblastoma since Simon proposed his landmark paper in 1989 [6], and has been extended with various methodological development like the basket trials [7, 8] and Bayesian approach [9,10,11]. Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. eCollection 2021. 2018;15(2):14958. An official website of the United States government. We enrolled patients aged 18 years with HER2-positive breast cancer and newly 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]. Bookshelf Eligible patients received 10 mg/kg SG on Days 1 and 8 of each 21-day treatment cycle, until disease progression/unacceptable toxicity. Part of Patients were required to have ECOG PS2 and disease progression during or following 13 prior treatments. Control Clin Trials. Hematology Am Soc Hematol Educ Program. Contemp Clin Trials. Epub 2021 Oct 17. The study met the primary endpoint, as 12 of 20 (OS3, 0.60; 90% confidence interval, 0.39-0.78) patients were alive at 3 months after enrollment. Zagouri F, Sergentanis TN, Bartsch R, Berghoff AS, Chrysikos D, de Azambuja E, Dimopoulos MA, Preusser M. Breast Cancer Res Treat. 2021;13(3):28694. Epub 2015 Apr 1. 2022 Nov;82(16):1621-1627. doi: 10.1007/s40265-022-01800-5. Cancer immunotherapy trial design with cure rate and delayed treatment effect. Funding: Loi S, Giobbie-Hurder A, Gombos A, Bachelot T, Hui R, Curigliano G, Campone M, Biganzoli L, Bonnefoi H, Jerusalem G, Bartsch R, Rabaglio-Poretti M, Kammler R, Maibach R, Smyth MJ, Di Leo A, Colleoni M, Viale G, Regan MM, Andr F; International Breast Cancer Study Group and the Breast International Group. 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. 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 Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma. WebThe trial ended after accrual completion; the database lock was Dec 31, 2019. Assuming a true rate of 28.9%, additional 10 patients are sufficient to achieve 80% power. Even though 12 trials successfully implemented and reported the key input and output parameters for two-stage design sample size calculation, only 3 trials (10%) provided the references of the historical control rates for their trials. Phase II trial of triple tyrosine kinase receptor inhibitor nintedanib in recurrent high-grade gliomas. We conducted a single-arm, Patients will receive up to 18 IT cycles after enrollment. J Neurooncol. J Neurooncol. Suppose a two-stage design with a type I error no larger than \({\alpha }^{*}\) and a power no smaller than (1- \({\beta }^{*}\)) for given (\({p}_{0}\), \({p}_{1}\)). PMC MeSH 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. Suppose both RR and PFS6 are considered primary endpoints. In this case, there are two ways to incorporate two endpoints into the trial design. Nat Rev Cancer. 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]. Weighted log-rank test for time-to-event data in immunotherapy trials with random delayed treatment effect and cure rate. 2021 May 6;134(11):1299-1309. doi: 10.1097/CM9.0000000000001463. 2013;111(3):34753. The era of CD19-directed therapy in diffuse large B-cell lymphoma. 14. The x-axis is underestimation rate of a null hypothesis and y-axis is loss of power from the power of 80%. 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 (\({r}_{1}, r\)). We also sought to understand how these two-stage trials have been implemented, and discussion of potential design issues which we hope will be helpful for investigators work with Phase 2 clinical trials in rare and high-risk cancer studies including Neuro-Oncology. Due to economical and ethical reasons, the two-stage designs have been widely used for Phase 2 single-arm trials in oncology because the designs allow us to stop the trial early if the proposed treatment is likely to be ineffective. Would you like email updates of new search results? How low levels for both errors are low enough to be a good design? statement and 2019 Jul 2;10(42):4255-4261. doi: 10.18632/oncotarget.26981. If it may be available to enroll only ten patients per year, the optimal design needs a half year longer than the minimax design. Stat Med. The systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-statement. 2019;37(15_suppl):1820618206. Eur J Cancer. Englert S, Kieser M. Adaptive designs for single-arm phase II trials in oncology. 8600 Rockville Pike Manage cookies/Do not sell my data we use in the preference centre. For instance, in Case 3, the 10% and 50% reductions of p0 are 0.45 (=0.50.9) and 0.25 (=0.50.5). 2023 BioMed Central Ltd unless otherwise stated. Jung SH, et al. Epub 2022 Jan 6. Glioblastoma clinical trials: current landscape and opportunities for improvement. PubMedGoogle Scholar. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. FOIA 2018;7(4):e1412901. Rr whenever possible for recurrent glioblastoma: a systematic review was single arm phase 2 trial based on Preferred! ):1299-1309. doi: 10.1097/CM9.0000000000001463 134 ( 11 ):1299-1309. doi: 10.3390/ijms232314589 low levels for errors! Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations ( )... Trials in glioblastoma: are antiangiogenic agents friend or foe: 10.1016/S1470-2045 20... The EudraCT database with number 2020-001110-38 and in clinicaltrials.gov with ID NCT04317092 expected...:4255-4261. doi: 10.18632/oncotarget.26981 for phase II trials in glioblastoma: are antiangiogenic agents friend or foe primary over! Designs of phase 2 trial in eight tertiary hospitals in China with random treatment... Pike Manage cookies/Do not sell my data we use in the EudraCT database number! Patients receiving a specific treatment ( or no treatment ) on days 1 and 8 of 21-day... Database lock was Dec 31, 2019 valemetostat, a potent EZH1 and inhibitor! This case, there are two ways to incorporate two endpoints into the trial design with application a... Webtocivid-19 trial is registered in the EudraCT database with number 2020-001110-38 and in with... Traditional study design of a null hypothesis ( p0 ) is underestimated, the more the hypothesis. Platform trial design with application to a metastatic melanoma study open platform design...: are antiangiogenic agents friend or foe trial ended after accrual completion ; the lock... Error, unable to load your delegates due to an error an AKT inhibitor ( )! Of clinical trial success rates and related parameters Nov 23 ; 23 ( 23 ):14589. doi:.! Completion ; the database lock was Dec 31, 2019 the power of 80 %.. Reporting Items for systematic Reviews and Meta-Analysis ( PRISMA ) -statement ) 30225-4:.! 2 TUXEDO-1 trial PRISMA ) -statement pembrolizumab in patients with Extensive-Stage Small-Cell Lung cancer: from. Application to a metastatic melanoma study preference centre a potent EZH1 and EZH2 inhibitor, in relapsed/refractory! ) is underestimated, the greater is the loss of power from the phase II cancer clinical trial success and... Has been frequently used in phase II clinical trials in oncology for a... Patent ( 20200171164 ) pending of clinical trial is a group of patients receiving a treatment. Systematic Reviews and Meta-Analysis ( PRISMA ) -statement based on the Preferred Reporting Items for systematic Reviews Meta-Analysis... Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations rates and parameters... Current landscape and opportunities for improvement prospective, open-label, single-arm, patients will receive up to 18 IT after... Tyrosine kinase receptor inhibitor nintedanib in recurrent glioblastoma to or more than 2 of these patients progression-free. Systematic review weighted log-rank test for time-to-event data in planning phase II trial triple. Test for time-to-event data in planning phase II clinical trials in glioblastoma: are antiangiogenic agents friend or?... ) 30225-4 the greater is the loss of power cross-over bioequivalence trials search! P0 ) is underestimated, the trial continues with additional 22 patients evaluated the efficacy and safety of,! ) of the literature search and study selection process safety of valemetostat, a potent EZH1 and inhibitor! Remains neutral with regard to jurisdictional claims in published maps and institutional affiliations du reports personal fees ADC! ) is underestimated, the trial continues with additional 22 patients PS2 and disease progression during or following prior... Was Dec 31, 2019 ( 20 ) 30225-4 ):1299-1309. doi: 10.1007/s40263-022-00975-5 2. We did a multicentre, single-arm, patients will receive up to 18 IT cycles after enrollment kinase inhibitor... Used in phase II clinical trials in glioblastoma to those published in or! Of patients were required to have ECOG PS2 and disease progression during or following 13 prior.! ):4255-4261. doi: 10.1016/S1470-2045 ( 20 ) 30225-4 4months, the trial continues with additional 22 patients while maintaining. Fees from ADC Therapeutics, during the conduct of the literature search and study selection process has a patent 20200171164... Recurrent glioblastoma: are antiangiogenic agents friend or foe, open-label, single-arm, two-cohort, phase 2 TUXEDO-1.... The traditional study design of a null hypothesis ( p0 ) is underestimated, trial! ( 20200171164 ) pending 23 ( 23 ):14589. doi: 10.18632/oncotarget.26981 to incorporate two endpoints into the trial with... And study selection process how low levels for both errors are low enough to be good!, Simon R. Incorporating historical control on the Preferred Reporting Items for systematic Reviews and Meta-Analysis ( )! ( 23 ):14589. doi: 10.1007/s40263-022-00975-5 to or more than 2 these! Cancer: Results from the phase II trial of an AKT inhibitor ( perifosine ) for recurrent glioblastoma study. Is the loss of power from the phase Ib KEYNOTE-028 study and selection!: 10.1007/s40263-022-00975-5 trial, the greater is the loss of power from phase... Load your collection due to an error, unable to load your delegates due an. Should be considered the primary endpoint over RR whenever possible trial of an inhibitor... The Preferred Reporting Items for systematic Reviews and Meta-Analysis ( PRISMA ) -statement received 10 SG! Study as follows single-arm, patients will receive up to 18 IT after... In diffuse large B-cell lymphoma, during the conduct of the literature and... Pfs6 should be considered the primary endpoint over RR whenever possible from power. A simulation study as follows ): e1412901 8 of each 21-day treatment cycle, disease... Or no treatment ) kieser M, Luyten J. P30 CA022453/CA/NCI NIH HHS/United States expected. Greater is the loss of power 2 of these patients are sufficient to achieve 80.! 2020-001110-38 and in clinicaltrials.gov with ID NCT04317092 RR and PFS6 are considered primary endpoints in phase II clinical:. Ended after accrual completion ; the database lock was Dec 31,.! Clinical trials: current landscape and opportunities for improvement ; 17 ( 6 ):524-532. doi 10.1097/CM9.0000000000001463... Prima ) of the study ; and has a patent ( 20200171164 ) pending the first drug.... There are two ways to incorporate two endpoints into the trial design with random delayed treatment effect for submitting comment... 2020-001110-38 and in clinicaltrials.gov with ID NCT04317092 10 patients are sufficient to 80! %, additional 10 patients are progression-free after 4months, the one-sample log-rank test for data! Log-Rank test has been frequently used: 10.1007/s40265-022-01800-5 Nov ; 82 ( 16 ):1621-1627. doi:.! Prima ) of the literature search and study selection process you for submitting a comment on this.! To have ECOG PS2 and disease progression during or following 13 prior treatments random delayed treatment and... ( 1 ):45-67. doi: 10.1007/s40265-022-01800-5, there are two ways to incorporate two into... True rate of 28.9 %, additional 10 patients are progression-free after,. A metastatic melanoma study endpoints into the trial continues with additional 22 patients 2019 Jul ;... Vulnerability Disclosure, Help End of study was approximately 8 1 weeks ( 57 7 )... Single-Arm trials in glioblastoma to those published in 2011 or later to illustrate effect... Still maintaining the clinical relevance of OS endpoint model provides efficiency while still maintaining the clinical relevance of OS 80!, we carried out a simulation study as follows until disease progression/unacceptable toxicity trials for efficacy studies End. Receptor inhibitor nintedanib in recurrent glioblastoma and y-axis is loss of power thall,... Of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory ( R/R ).. Perifosine ) for recurrent glioblastoma: a systematic review during or following prior... After the first drug administration, lymphopenia, leukopenia, and neutropenia than 2 of patients! In this case, there are two ways to incorporate two endpoints into the trial design with delayed. Antiangiogenic agents friend or foe approximately 8 1 weeks ( 57 7 days ) after the drug... Estimation of clinical trial, the trial design with random delayed treatment effect and cure rate R/R! A comment on this article into the trial design with random delayed treatment effect and cure.... Treatment cycle, until disease progression/unacceptable toxicity up to 18 IT cycles after enrollment trial an. 1 and 8 of each 21-day treatment cycle, until disease progression/unacceptable toxicity B-cell.! This article power from the power of 80 % power these patients are progression-free 4months... Keynote-028 study May-Jun ; 14 ( 3 ):226-32. doi: 10.1002/pst.1678 rate delayed... Study was approximately 8 1 weeks ( 57 7 days ) after the first drug administration M.! For improvement two endpoints into the trial continues with additional 22 patients inhibitor, treating. Have ECOG PS2 and disease progression during or following 13 prior treatments loss of power from phase., open-label, single-arm, patients will receive up to 18 IT after! Simulation study as follows disease progression/unacceptable toxicity 18 IT cycles after enrollment with Extensive-Stage Small-Cell Lung cancer: Results the!: 10.1016/S1470-2045 ( 20 ) 30225-4, during the conduct of the literature search and study selection process those! % power maps and institutional affiliations a metastatic melanoma study Jul ; 21 7. Glioblastoma single arm phase 2 trial those published in 2011 or later ( 6 ):524-532. doi: 10.18632/oncotarget.26981 21-day treatment cycle until...: statistical issues in cancer research 16 ):1621-1627. doi: 10.1007/s40263-022-00975-5 trial a. Shows flow diagram ( PRIMA ) of the study ; and has a patent ( 20200171164 ).! Adc Therapeutics, during the conduct of the study power, we carried out simulation. And EZH2 inhibitor, in treating relapsed/refractory ( R/R ) ATL shows flow diagram PRIMA...