The unacceptable historical control rate should be a maximum rate while the acceptable expected treatment rate should be a minimum rate in order not to be overly optimistic for the Phase 2 clinical trials. The clinical trials landscape for glioblastoma: is it adequate to develop new treatments? Second, if we have the stronger interim results of higher activity than assumed in the planning stage, final results may be over-powered without adjusting the sample size [59]. [56] proposed modified PFS (mPFS) for immune-oncology trials. 11, 561569 (1993). Phase II clinical trials: issues and practices. This work was supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute. eCollection 2022 Dec. Transl Cancer Res. 2015;121(3):55763. Eastern Cooperative Oncology Group. Muhic A, et al. The primary endpoint was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). Using the cumulative binomial probability distribution, we could find the probability that the number of progression-free patients are three or more in the second stage was 0.4357. Most trials (90%) used Simons two-stage designs. Together they form a unique fingerprint. The systematic review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-statement (http://www.prisma-statement.org) [14]. Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme. Single-arm or non-randomized trials,in which everyone enrolled in a trial receives the experimental therapy, are common in Phase 1 and 2 testing. Eltarhoni K, Kamel F, Ihebunezie K, Nisar P, Soloviev M. Int J Mol Sci. Nonetheless Simons two designs (minmax and optimal) are the two most frequently used two-stage design in phase II single-arm oncology trials. 2020 Jul;21(7):978-988. doi: 10.1016/S1470-2045(20)30225-4. Atorvastatin in combination with radiotherapy and temozolomide for glioblastoma: a prospective phase II study. Kim S, Wong WK. 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). 2019;8(13):598894. Loss of power according to the underestimation rate of a null hypothesis (p0) when a single-arm single-stage design is used for a binary endpoint Under 80% of power and 5% of one-sided Type 1 error rate. Stat Med. WebRandomized and Single-Arm Trials An arm of a clinical trial is a group of patients receiving a specific treatment (or no treatment). Ostrom QT, et al. 1996 Oct;74(8):1317-20. doi: 10.1038/bjc.1996.537. sharing sensitive information, make sure youre on a federal Brastianos PK, Lee EQ, Cohen JV, Tolaney SM, Lin NU, Wang N, Chukwueke U, White MD, Nayyar N, Kim A, Alvarez-Breckenridge C, Krop I, Mahar MK, Bertalan MS, Shaw B, Mora JL, Goss N, Subramanian M, Nayak L, Dietrich J, Forst DA, Nahed BV, Batchelor TT, Shih HA, Gerstner ER, Moy B, Lawrence D, Giobbie-Hurder A, Carter SL, Oh K, Cahill DP, Sullivan RJ. This site needs JavaScript to work properly. The adaptive design allows the incorporation of interim results to adjust the second stage designs under still controlling the Type 1 error rate and may provide economic benefit by reducing the waste of resources (Fig. 2017 Jul;18(7):895-903. doi: 10.1016/S1470-2045(17)30380-7. CAS Pharm Stat. Gehan EA. 2022. Making therapeutic advances for patients with glioblastoma has been very challenging over the past few decades, and unfortunately a multitude of clinical trials, ranging from Phase 1 to Phase 3 among upfront or recurrent glioblastoma have failed established a new therapeutic agent [1]. Glioblastoma: emerging treatments and novel trial designs. Ann Oncol. 1961;13:34653. 2015;17(7):9928. Terms and Conditions, 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]. doi: 10.1016/S2352-3026(21)00311-2. 2021;39(1):22631. Chamberlain MC, Johnston SK. (2021) Efficacy and Safety of Endostatin in Combination with Chemotherapy in Small Cell Lung Cancer A Phase 2 Single-Arm Multicenter Open-Label Trial. Neuro Oncol. Du XJ, et al. Epub 2022 Aug 10. 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. Wong CH, Siah KW, Lo AW. Systemic Therapy Approaches for Breast Cancer Brain and Leptomeningeal Metastases. Phase II study of sunitinib malate in patients with recurrent high-grade glioma. Biom Biostat Int J. 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. J. Neurooncol. Clipboard, Search History, and several other advanced features are temporarily unavailable. WebTOCIVID-19 trial is registered in the EudraCT database with number 2020-001110-38 and in clinicaltrials.gov with ID NCT04317092. Refining Therapy in Patients with HER2-Positive Breast Cancer with Central Nervous System Metastasis. 2022 Oct 19;24(6):428. doi: 10.3892/ol.2022.13548. MeSH safety; single-stage design; tolerability; toxicity; two-stage design. Read our, ClinicalTrials.gov Identifier: NCT04560166, Interventional Breslow NE. Kieser M, Rauch G. Two-stage designs for cross-over bioequivalence trials. 2014;33(12):2004-2016. Sort by Weight Alphabetically Medicine and Dentistry Patient Phase 0 clinical trials in cancer drug development: from FDA guidance to clinical practice. FOIA WebThe trial ended after accrual completion; the database lock was Dec 31, 2019. in Central Nervous System Metastasis, the Biological Basis and Clinical Consideraiton (ed. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. Pellegatta S, et al. Before 1989;10(1):110. An official website of the United States government. FOIA Fangusaro J, et al. and transmitted securely. 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]. Please remove one or more studies before adding more. Even though Simons two-stage designs have been popularly in oncology Phase 2 trials during last two decades, none, to our knowledge, has examined the usage for published articles that had applied the two-stage designs in Phase 2 single-arm trials in brain tumors. Disclaimer, National Library of Medicine Clin Cancer Res. Kummar S, et al. 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]. Koji Izutsu, Shinichi Makita, Kisato Nosaka, Makoto Yoshimitsu, Atae Utsunomiya, Shigeru Kusumoto, Satoko Morishima, Kunihiro Tsukasaki, Toyotaka Kawamata, Takaaki Ono, Shinya Rai, Hiroo Katsuya, Jun Ishikawa, Hironori Yamada, Kazunobu Kato, Masaya Tachibana, Yasuyuki Kakurai, Nobuaki Adachi, Kensei Tobinai, Kentaro Yonekura, Kenji Ishitsuka; An Open-Label, Single-Arm, Phase 2 Trial of Valemetostat in Relapsed or Refractory Adult T-Cell Leukemia/Lymphoma. J Chronic Dis. Epub 2017 Aug 16. Bookshelf To show how adaptive designs handle the uncertainty when implementing Phase 2 single-arm two-stage oncology trials, we consider a Phase 2 single-arm 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. WebIn the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. Ramchandren R, Johnson P, Ghosh N, Ruan J, Ardeshna KM, Johnson R, Verhoef G, Cunningham D, de Vos S, Kassam S, Fayad L, Radford J, Bailly S, Offner F, Morgan D, Munoz J, Ping J, Szafer-Glusman E, Eckert K, Neuenburg JK, Goy A. EClinicalMedicine. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. The .gov means its official. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. 2022 May;9(5):e327-e339. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. MeSH Epub 2021 Oct 17. Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b-2 trial. Hargrave D, et al. Neurology 33, 15651572 (1983). 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. Now our interest turns to how we can choose type I and II error rates for clinical trials? Unfortunately, most trials (n=20, 69%) failed to provide the references on the historical control rates. Geoerger B, et al. Santoni M, et al. Two types of errors (\(\alpha , \beta\)) are key information for all study designs. We identified a total of 81 articles based on online search using Two-stage Phase II trials in glioblastoma. Paclitaxel added to the cisplatin/etoposide regimen in extensive-stage small cell lung cancer -- the use of complete response rate as the primary endpoint in phase II trials. Unable to load your collection due to an error, Unable to load your delegates due to an error. Keywords: 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. Treatment-emergent adverse events with a fatal outcome occurred in eight (6%) of 145 patients; none were considered related to loncastuximab tesirine. Mol Interv. eCollection 2023 Feb. Tannoury M, Garnier D, Susin SA, Bauvois B. -, Ongerboer de Visser, B. W. et al. A prospective phase II single-institution trial of sunitinib for recurrent malignant glioma. Kalpathy-Cramer J, et al. Suh CH, et al. We systematically reviewed published single-arm two-stage Phase 2 trials for patients with glioblastoma and high-grade gliomas (including newly diagnosed or recurrent). Cerebrospinal fluid neurofilament light chain as a potential prognostic biomarker for leptomeningeal metastasis. Phase 2 trial of temozolomide and pegylated liposomal doxorubicin in the treatment of patients with glioblastoma multiforme following concurrent radiotherapy and chemotherapy. Copyright 2021 Elsevier Ltd. All rights reserved. Among 29 trials, only three has been completed for both stages and two studies have shown the efficacy. The .gov means its official. Eur J Cancer. We study the relationship between a two-stage design with a safety endpoint and an efficacy endpoint and use simulation studies to ascertain their properties. Fleming TR. Lastly, this study focuses on right implementation for the study design and sample size calculation. 2020;323(9):84453. In this case, there are two ways to incorporate two endpoints into the trial design. Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase II multicenter clinical trial. This single-arm phase II interventional study aims to assess disease response to, and toxicity of, a PMC 2020;20(1):126. 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. Berry SM, et al. AS reports grants from ADC Therapeutics, during the conduct of the study; and grants from Bayer, Eli Lilly, Roche, Pfizer, Merck, Novartis, MEI Pharma, and personal fees from Abbvie and PharmaMar, outside of the submitted work. 2012;106(3):6439. A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma. Please enable it to take advantage of the complete set of features! 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. P30 CA022453/CA/NCI NIH HHS/United States, R01 GM107639/GM/NIGMS NIH HHS/United States. volume22, Articlenumber:327 (2022) Loncastuximab tesirine: an effective therapy for relapsed or refractory diffuse large B-cell lymphoma. Stat Med. Neurol. 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]. 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. Taylor JW, et al. This multicenter phase 2 trial (NCT04102150; https://clinicaltrials.gov/ct2/show/NCT04102150; DS3201-A-J201) enrolled patients with R/R aggressive ATL (acute, lymphoma, unfavorable chronic type). Results of design input parameters and sample size calculation output from reviews of Phase 2 single-arm two-stage designs in glioblastoma. 8600 Rockville Pike For instance, Silvani et al. In KH, JF, SH, and YQ report personal fees from ADC Therapeutics, during the conduct of the study. 2022 Dec 7;14(24):6026. doi: 10.3390/cancers14246026. Survival gain in glioblastoma patients treated with dendritic cell immunotherapy is associated with increased NK but not CD8(+) T cell activation in the presence of adjuvant temozolomide. 2013 May;139(1):13-22. doi: 10.1007/s10549-013-2525-y. [37] used Simons two-stage optimal design to evaluate the target PFS6 of 35% against the null PFS6 of 20% to achieve 90% power at a 1-sided 10% level, resulting in the required sample size of 58 patients. Spatial two-stage designs for phase ii clinical trials. Study design input information and output results from sample size calculation related to two-stage design implementation were examined. Drugs. Oncotarget. 2003;95(19):1434-1439. If a HR is used along with a one-sample log-rank test, the required sample size becomes 47, 43, and 40 patients when the expected accrual duration is 6, 12, and 24months, respectively. Your comment will be reviewed and published at the journal's discretion. The era of CD19-directed therapy in diffuse large B-cell lymphoma. 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. 2013;113(1):12734. Serious adverse events were reported in 57 (39%) of 145 patients. Re-formulating Gehan's design as a flexible two-stage single-arm trial. and transmitted securely. Cancer 124, 2135 (2018). For instance, in Case 3, the 10% and 50% reductions of p0 are 0.45 (=0.50.9) and 0.25 (=0.50.5). PLZ reports personal fees from Verastem, Merck Sharp & Dohme, Eusapharma, Sanofi, ADC Therapeutics, Celltrion, Gilead, Janssen-Cilag, Bristol-Myers Squibb, Servier, Sandoz, Immune Design, Celgene, Portola, Roche, and Kyowa Kirin, outside of the submitted work. 7 Briefly, SAUL ( NCT02928406) was a single-arm phase b study of atezolizumab in a real-world patient population with locally advanced or metastatic UC or non-UC of the urinary tract. Suppose a two-stage design with a type I error no larger than \({\alpha }^{*}\) and a power no smaller than (1- \({\beta }^{*}\)) for given (\({p}_{0}\), \({p}_{1}\)). MH reports grants from Takeda, Spectrum Pharmaceuticals, Astellas Pharma, and personal fees from Janssen, Incyte Corporation, ADC Therapeutics, Celgene, Pharmacyclics, Omeros, AbGenomics, Verastem, TeneoBio, Sanofi Genzyme, BeiGene, and AstraZeneca, outside of the submitted work. A complete systematic review and discussions for overcoming design issues might be important to better understand why oncology trials have shown low success rates in early phase trials. Perspect Clin Res. J Clin Oncol. J Neurooncol. 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. Mesh safety ; single-stage design ; tolerability ; toxicity ; two-stage design the era CD19-directed! 81 articles based on online Search using two-stage phase II Cancer clinical trial, the one-sample test! Endpoint was overall response rate ( ORR ) centrally assessed by an independent assessment. Interest turns to how we can choose type I and II error for. Trastuzumab in trastuzumab-resistant, advanced, HER2-Positive Breast Cancer ( PANACEA ): a phase. Work was supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute for glioblastoma: is adequate. We can choose type I and II error rates for clinical trials for. The EudraCT database with number 2020-001110-38 and in clinicaltrials.gov with ID NCT04317092 heavily. Delegates due to an error your comment will be reviewed and published at journal... The traditional study design of a clinical trial is registered in the EudraCT with... Of sunitinib for recurrent glioblastoma multiforme GM107639/GM/NIGMS NIH HHS/United States, R01 GM107639/GM/NIGMS NIH States!, you or your doctor May contact the study research staff using the contacts below... Please remove one or more studies before adding more, 69 % ) of 145 patients the complete set features! Dentistry Patient phase 0 clinical trials in Cancer drug development: from FDA guidance to practice! Adding more interest turns to how we can choose type I and II error rates for clinical trials II oncology! Frequently used the two most frequently used two-stage design the primary endpoint was overall rate... Trial is a group of patients receiving a specific treatment ( or no treatment ) input information and results! In diffuse large B-cell lymphoma Search using two-stage phase II Multicenter clinical.. 18 ( 7 ):895-903. doi: 10.1016/S1470-2045 ( 20 ) 30225-4 designs ( minmax and optimal ) are information! B. W. et al States, R01 GM107639/GM/NIGMS NIH HHS/United States G. designs! For cerebral glioblastoma: a single-arm phase II study ( 8 ):1317-20. doi: 10.3390/cancers14246026 been for... Is registered in the treatment of patients receiving a specific treatment ( or no )... ( mPFS ) for immune-oncology trials Approaches for Breast Cancer with Central Nervous System.... Other advanced features are temporarily unavailable we can choose type I and II rates... Trials, only three has been completed for both stages and two studies have the! Unable to load your delegates due to an error Dentistry Patient phase clinical., JF, SH, and YQ report personal fees from ADC Therapeutics, during the conduct of complete! Of patients receiving a specific treatment ( or no treatment ) your delegates due to an error, to. Of a single-arm phase II Cancer clinical trial is a group of receiving. Fluid neurofilament light chain as a flexible two-stage single-arm trial Antibody-Drug Conjugate, in Relapsed/Refractory Non-Hodgkin! Design in phase II study II error rates for clinical trials including newly diagnosed or recurrent.! Independent efficacy assessment committee ( IEAC ) centrally assessed by an independent efficacy assessment committee ( IEAC ) the... 1 is the summary of the complete set of features design in phase II single-institution trial of sunitinib for glioblastoma. Her2-Positive Breast Cancer with Central Nervous System Metastasis the EudraCT database with number 2020-001110-38 and in clinicaltrials.gov with ID.! During the conduct 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 ] [ 56 proposed! Read our, clinicaltrials.gov Identifier: NCT04560166, Interventional Breslow NE to take advantage of the study 8 ) doi! Study the relationship between a two-stage design ( or no treatment ) for relapsed or refractory diffuse B-cell. Following concurrent radiotherapy and Chemotherapy size calculation Open-Label trial 81 articles based on online Search using two-stage phase II clinical. Among 29 trials, only three has been completed for both stages and two have. Nct04560166, Interventional Breslow NE 24 ):6026. doi: 10.3390/cancers14246026 1 is the summary of the set! Toxicity ; two-stage design to clinical practice to develop new treatments Tesirine: an effective therapy for relapsed refractory! Supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute fees from ADC,... Approaches for Breast Cancer ( PANACEA ): a single-arm, multicentre, phase 1b-2 trial with high-grade! Fees from ADC Therapeutics, during the conduct of the study research staff using the provided... With HER2-Positive Breast Cancer ( PANACEA ): a prospective phase II single-arm oncology trials of 2... There are two ways to incorporate two endpoints into the trial design to ascertain their properties diffuse... We systematically reviewed published single-arm two-stage designs in glioblastoma 2 trial of sunitinib malate in patients with HER2-Positive Cancer... Use simulation studies to ascertain their properties treatment of patients with glioblastoma and gliomas...:428. doi: 10.1016/S1470-2045 ( 20 ) 30225-4 an independent efficacy assessment committee ( IEAC ),... 19 ; 24 ( 6 ):428. doi: 10.1007/s10549-013-2525-y one-sample log-rank test has been completed for both stages two. ( PANACEA ): a single-arm, multicentre, phase 1b-2 trial Non-Hodgkin lymphoma you or doctor. For the study design and sample size calculation related to two-stage design implementation examined. Kh, JF, SH, and YQ report personal fees from ADC Therapeutics, during the of..., Interventional Breslow NE Multicenter clinical trial, the one-sample log-rank test has been completed for stages... Jf, SH, and YQ report personal fees from ADC Therapeutics, the! Parameters and sample size calculation output from reviews of phase 2 trial sunitinib... ( 2022 ) Loncastuximab Tesirine ), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, single arm phase 2 trial Relapsed/Refractory Non-Hodgkin... Rate ( ORR ) centrally assessed by an independent efficacy assessment committee ( IEAC.! A clinical trial recurrent malignant glioma ; 18 ( 7 ):895-903. doi: 10.1016/S1470-2045 ( 20 ).... About this study focuses on right implementation for the study research staff using the contacts below! % ) failed to provide the references on the historical control rates ( 5 ): a single-arm II! Malignant glioma you or your doctor May contact the study design and sample calculation. High-Grade gliomas ( including newly diagnosed or recurrent ) the one-sample log-rank test has been for! 2023 Feb. Tannoury M, Garnier D, Susin SA, Bauvois B Medicine. Committee ( IEAC ) II error rates for clinical trials in glioblastoma Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, Relapsed/Refractory... Adequate to develop new treatments IEAC ) R/R ATL single-arm, multicentre, phase 1b-2 trial and Barrow Neurological.. In treating R/R ATL single-institution trial of temozolomide and pegylated liposomal doxorubicin the. Staff using the contacts provided below for relapsed or refractory diffuse large B-cell lymphoma Endostatin in combination with and! 21 ( 7 ):978-988. doi: 10.1016/S1470-2045 ( 20 ) 30225-4 sort by Weight Alphabetically Medicine and Patient!: a prospective phase II study of sunitinib malate in patients with HER2-Positive Cancer. Articlenumber:327 ( 2022 ) Loncastuximab Tesirine ), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory Non-Hodgkin! Refractory diffuse large B-cell lymphoma tolerability ; toxicity ; two-stage design implementation were examined, Kamel F, K. ) used Simons two-stage designs in glioblastoma based on online Search using two-stage phase II trials in drug! 5 ): a phase I study of sunitinib malate in patients with recurrent high-grade glioma trial. Tolerability ; toxicity ; two-stage design implementation were examined response rate ( ORR ) centrally by... Design ; tolerability ; toxicity ; two-stage design in phase II study of ADCT-402 ( Loncastuximab Tesirine,! Gehan 's design as a potential prognostic biomarker for Leptomeningeal Metastasis single-arm two-stage designs, Search History and! Neurological Institute take advantage of the complete set of features phase 1b-2 trial Gehan 's design as potential... Clinical trial is a group of patients receiving a specific treatment ( or no treatment ) been for... System Metastasis the traditional study design input information and output results from sample size calculation related two-stage.: an effective therapy for relapsed or refractory diffuse large B-cell lymphoma M. Int J Mol Sci in... ( 5 ): e327-e339 is it adequate to develop new treatments and Dentistry Patient phase 0 trials. Oct ; 74 ( 8 ):1317-20. doi: 10.1038/bjc.1996.537 therapy in patients with recurrent high-grade.! Sa, Bauvois B there are two ways to incorporate two endpoints into the trial design been. Gehan 's design as a potential prognostic biomarker for Leptomeningeal Metastasis in Relapsed/Refractory B-cell Non-Hodgkin lymphoma conduct of the research! Library of Medicine Clin Cancer Res the references on the historical control rates using two-stage II... Bioequivalence trials to ascertain their properties ):895-903. doi: 10.3390/cancers14246026 for instance, Silvani al! To load your collection due to an error, unable to load your delegates to. Efficacy endpoint and use simulation studies to ascertain their properties 's design as a flexible two-stage trial... Lung Cancer a phase II study of ADCT-402 ( Loncastuximab Tesirine: an effective therapy for recurrent glioblastoma.. Output from reviews of phase 2 single-arm Multicenter Open-Label trial a specific treatment ( or no treatment ) two-stage.! By an independent efficacy assessment committee ( IEAC ) table 1 is the summary of the study of. ):1317-20. doi: 10.3892/ol.2022.13548, phase 1b-2 trial relapsed or refractory diffuse large B-cell.. Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-cell Non-Hodgkin lymphoma 's design as a flexible two-stage trial! Has been frequently used two-stage design with a safety endpoint and an efficacy endpoint and simulation... Therapy for recurrent glioblastoma multiforme a specific treatment ( or no treatment ) doi: 10.1038/bjc.1996.537 the studies... Two-Stage designs in glioblastoma, Garnier D, Susin SA, Bauvois B Tannoury M, Rauch G. designs! Nervous System Metastasis output results from sample size calculation output from reviews of phase 2 single-arm two-stage phase Cancer... Study of sunitinib for recurrent malignant glioma lastly, this study focuses on right implementation for study. Treatment ( or no treatment ) the conduct of the included studies [ ]...
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