Muhic A, et al. 2015;34(6):1031-1040. We can see that four and twelve studies utilized Simons minimax and optimal designs respectively, in Table 1. Wang Z-X, et al. Study design input information and output results from sample size calculation related to two-stage design implementation were examined. Eur J Cancer. Lancet Oncol. 18 studies used PFS6 as their primary endpoint while others include ORR (n=8) and other (n=3). Studies a U.S. FDA-regulated Drug Product: Studies a U.S. FDA-regulated Device Product: Irinotecan, solution for infusion (20 mg/mL), Temozolomide, capsules (5 mg, 20 mg and 100 mg), The humanized immunoglobulin isotype G (IgG1) monoclonal antibody (mAb) naxitamab, solution for infusion (4 mg/mL), Sargramostim (GM-CSF), lyophilized 250 g single use vial (250 g/vial), Overall response rate (ORR) [TimeFrame:84 days], ORR after 2 cycles [TimeFrame:42 days], Duration of response (DoR) [TimeFrame:2 years], Complete response (CR) rate [TimeFrame:84 days], Time to first subsequent therapy [TimeFrame:3 years], Progression free survival (PFS) [TimeFrame:3 years], Overall survival (OS) [TimeFrame:3 years], Overall survival (OS) [TimeFrame:1 year], Overall survival (OS) at 2 years [TimeFrame:2 year], Receipt of Standard of Care (SoC) frontline induction/consolidation therapy (including surgery, chemotherapy, ASCT, MIBG, radiotherapy, immunotherapy, or retinoids), verified first progression during multi-drug frontline treatment or, verified first episode of relapse, defined as recurrence after response to frontline treatment, or, verified first designation of refractory disease, defined as persistent metastatic disease (SD or minor response by INRC and MIBG curie score 3) detected at conclusion of at least 4 cycles of multi-drug induction chemotherapy on or according to a high-risk NB treatment protocol as defined above, Measurable tumor on CT/MRI scan that is MIBG-avid or demonstrates increased FDG uptake on PET scan, MIBG (Metaiodobenzylguanidine) scan with positive uptake at a minimum of one site. Eur J Cancer. Fifty-six of the 70 (80%) participants became desensitized to peanuts. Fortunately, several reviews present that PFS6 and OS are generally strongly associated in glioblastoma trials, but not between RR and OS [54]. Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study. To improve test power, we proposed a new weighted one-sample log-rank test and provided a sample size calculation formula for designing trials. Let us now assume that 4 (36.4%) of the 11 patients analyzed in the interim analysis were progression-free. Trials involving several arms, or randomized Provided by the Springer Nature SharedIt content-sharing initiative. PLoS One. Phase II clinical trials with time-to-event endpoints: optimal two-stage designs with one-sample log-rank test. 2021;13(3):28694. Thall PF, Simon R. Incorporating historical control data in planning phase II clinical trials. Lassen U, 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. This work was supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute. MeSH 133, 419427 (2017). The Follow-Up period ends 2 years after End of Treatment. Cancer immunotherapy trial design with cure rate and delayed treatment effect. in Central Nervous System Metastasis, the Biological Basis and Clinical Consideraiton (ed. Epub 2019 Feb 11. How low levels for both errors are low enough to be a good design? Before Chu Y, Yuan Y. OPTIM-ARTSAn adaptive phase II open platform trial design with application to a metastatic melanoma study. Phase 0 clinical trials in cancer drug development: from FDA guidance to clinical practice. Article WebAn increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal 1-3. When there is uncertainty among endpoints as a surrogate for OS, several primary endpoints can be employed together. 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. Federal government websites often end in .gov or .mil. Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase II multicenter clinical trial. (Clinical Trial). Clipboard, Search History, and several other advanced features are temporarily unavailable. Among appropriately implemented 12 trials, discouragingly only 3 trials (10%) explained the reference information of historical control rates. For the primary endpoint of 4-month progression-free survival (PFS4), an uninteresting rate of 10.9% obtained from historical controls and an anticipated rate of 28.9% were assumed. 2017;131(3):60310. Warren KE, et al. Treatment-emergent adverse events (TEAEs) were manageable. 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. Epub 2015 Apr 1. Among 29 trials, only three has been completed for both stages and two studies have shown the efficacy. 2015;17(7):9928. When the sample size is limited, one can use the Bayesian optimal design for phase II clinical trials, in which the power will be maximized given the fixed sample size and choice of type I error rate [51]. 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. Bookshelf Lee EQ, et al. Copyright 2022 American Society of Hematology. 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. Methods: In this open-label, single-arm, single-center, exploratory phase II study, 10 patients (20 eyes) received EG-Mirotin once a day (3 mg/1.5 mL sterile saline) for 5 days and were evaluated for ischemic index changes and safety. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. 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. Anticancer Res. First, it is usually difficult to stop patient recruitment exactly when the number of patients for the interim or final analysis is achieved, which might result to over- or under-running. 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. Why Should I Register and Submit Results? Vanderbeek AM, et al. Cancer immunotherapy trial design with random delayed treatment effect and cure rate. 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. Optimal, minimax and admissible two-stage design for phase II oncology clinical trials. Stat Med. 2010;28(11):193641. Bethesda, MD 20894, Web Policies The site is secure. WebThe SAUL study has been published. 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. Wouters and colleagues reported that U. S. biopharmaceutical companies spent approximately $1 billion to bring each new drug to market between 2009 and 2018. Sanai N. Phase 0 clinical trial strategies for the neurosurgical oncologist. An increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal1-3. Neuro Oncol. Hargrave D, et al. Bookshelf 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. An official website of the United States government. Yoo, W., Kim, S., Garcia, M. et al. 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. Pasqualini C, et al. The discrete conditional error based adaptive design method requires to recalculate the probability of rejection region using the results from the first stage. official website and that any information you provide is encrypted By using this website, you agree to our Bethesda, MD 20894, Web Policies 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 study using two-stage design [42], where Brenner and colleagues investigated a new treatment option of hypoxia activated evofosfamide (TH302) for patient with recurrent bevacizumab-refractory glioblastoma. 2021;39(1):22631. 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. Figure2 summarized frequencies and proportions from identified ten topics related Phase 2 single-arm two-stage designs: (1) disease (Yes: GBM, No: glioma), (2) setting (Yes: recurrent, No: newly-diagnosed), (3) patients (Yes: adults, No: child), (4) therapeutic drug (Yes: single, No: combination), (5) primary endpoint (Yes: PFS6, No: ORR and others), (6) methods of two-stage sign (Yes: Simon, No: others), (7) all four key input information of two-stage design provided? Among 29 trials reviewed systematically, 12 trails (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. 2018;74(2):529-537. WebSingle-dose carboplatin followed by involved-node radiotherapy for stage IIA and stage IIB seminoma (SAKK 01/10): a single-arm, multicentre, phase 2 trial Erstverffentlichung 2022 Kaley TJ, et al. Only three studies have been completed for both stages and two out of the three completed studies had shown the efficacy. Rubinstein LV, et al. Assuming a true rate of 28.9%, additional 10 patients are sufficient to achieve 80% power. To illustrate the effect of underestimated historical control on the study power, we carried out a simulation study as follows. Kalpathy-Cramer J, et al. 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]. Together they form a unique fingerprint. A treatment cycle is 21 days. 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 Epub 2021 Nov 15. 2019 Dec 1;25(23):6986-6994. doi: 10.1158/1078-0432.CCR-19-0711. A Simon two-stage design was used to compare a null hypothesis OS3 of 18% against an alternative of 43%. The primary endpoint was safety. Korean J Radiol. Phase 0 clinical trials: recommendations from the task force on methodology for the development of innovative cancer therapies. MeSH 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 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. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. 2022. 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. Brief Summary: An International, Single-Arm, Multicenter Phase 2 Trial. official website and that any information you provide is encrypted Safety and efficacy of decitabine in combination with temozolomide in metastatic melanoma: a phase I/II study and pharmacokinetic analysis. 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. Kieser M, Rauch G. Two-stage designs for cross-over bioequivalence trials. 2020;20(1):126. Tang H, et al. Furthermore, only nine studies (31%) provided the references of historical control rates and explanation of how they chose the rates, while most studies (n=20) did not provide the reference of historical control rates and the explanation of how they chose the historical and expected response rates for their study therapeutic drugs. 2008;14(12):367582. The followings were key words for the literature search as index terms or free-text words: phase II trials, glioblastoma, and two-stage design. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). Phase II open-label study of nintedanib in patients with recurrent glioblastoma multiforme. 1961;13:34653. The era of CD19-directed therapy in diffuse large B-cell lymphoma. Optimized image-based surrogate endpoints in targeted therapies for glioblastoma: a systematic review and meta-analysis of phase iii randomized controlled trials. 2016 Dec;34(34):4086-4093. doi: 10.1200/JCO.2016.67.7732. 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. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. 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. 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. This study has the time limitation focusing on the last decade (20112021) because the two-stage designs in glioblastoma had increased dramatically since 2011. We conducted a single-arm, phase 2 study of pembrolizumab in patients with solid tumor malignancies and LMD (NCT02886585). 2018 Sep;17(5):541-554. doi: 10.1002/pst.1878. 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]. The median PFS of 4.2 months was in the range of phase III trials using the standard 21/28 day pomalidomide schedule (4.04.6 months) [1, 2]. 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]. Clin Trials. Keywords: Leveraging Molecular and Immune-Based Therapies in Leptomeningeal Metastases. KH, JF, SH, and YQ report personal fees from ADC Therapeutics, during the conduct of the study. Let us assume that the result of a two-stage design indicates 18 and 23 in total patients for the minimax and optimal respectively. Unlike a survival rate at a specific time point, a HR is not a point estimate and uses all the information in the entire survival curve. Stat Med. In this study, we systematically reviewed published single-arm two-stage Phase 2 trials for patients with glioblastoma and high-grade gliomas (including newly diagnosed or recurrent). There was no language restriction, but only complete papers published in peer-reviewed journals were considered. Since the two-stage design of Phase 2 trials aims to make a conclusion of go or no-go to the next second stage, the sample size calculation of two-stage designs produces the number of patients in first stage (\({n}_{1}\)) and the response number which is eligible to move to the second stage (\({r}_{1}\)). Study record managers: refer to the Data Element Definitions if submitting registration or results information. 2021 Feb 8;16(2):e0246448. Burzynski SR, et al. Multistage designs for phase II clinical trials: statistical issues in cancer research. 2020 Mar 15;39(6):698-708. doi: 10.1002/sim.8440. Gehan EA. End of study was approximately 8 1 weeks (57 7 days) after the first drug administration. 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]. Gupta UC, et al. sharing sensitive information, make sure youre on a federal Kwak M, Jung S-H. 2020 Jul;21(7):978-988. doi: 10.1016/S1470-2045(20)30225-4. 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, 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. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. Neurosurg. 1800 M Street NW, Suite 1050 South,Washington, DC 20036Phone: (202) 944-6700. Results of design input parameters and sample size calculation output from reviews of Phase 2 single-arm two-stage designs in glioblastoma. For general information, Learn About Clinical Studies. A better way to avoid the potential issues is to use a hazard ratio (HR). A prospective phase II single-institution trial of sunitinib for recurrent malignant glioma. Re-formulating Gehan's design as a flexible two-stage single-arm trial. Phase 2 study of Pomalidomide (CC-4047) monotherapy for children and young adults with recurrent or progressive primary brain tumors. 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%]). 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. The .gov means its official. Treatment-emergent adverse events with a fatal outcome occurred in eight (6%) of 145 patients; none were considered related to loncastuximab tesirine. 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. 2019;8(13):598894. 2015 May-Jun;14(3):226-32. doi: 10.1002/pst.1678. Designing phase 0 cancer clinical trials. Disclaimer, National Library of Medicine Pellegatta S, et al. Lastly, this study focuses on right implementation for the study design and sample size calculation. Clinical end points in recurrent glioblastoma: are antiangiogenic agents friend or foe? 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. 1975;43(1):45-57. Phase 2 trial of temozolomide and pegylated liposomal doxorubicin in the treatment of patients with glioblastoma multiforme following concurrent radiotherapy and chemotherapy. Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, 1R01CA244975-01/U.S. 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. Stat Med. J Clin Oncol. 2015;34(16):240316. Detailed Description: This is an international, single-arm, multicenter phase 2 trial, in Nat Commun. Adaptive two-stage designs for single-arm phase IIA cancer clinical trials. 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. and transmitted securely. 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. 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). Treatment-emergent adverse events (TEAEs) were manageable. The https:// ensures that you are connecting to the Stat Biopharma Res. Phase II study of tivozanib, an oral VEGFR inhibitor, in patients with recurrent glioblastoma. Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next? 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]. Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma. Clin Cancer Res. Eligible patients received 10 mg/kg SG on Days 1 and 8 of each 21-day treatment cycle, until disease progression/unacceptable toxicity. 2011;105(3):52330. Second, if the patient accrual rate is low, the minimax design is more attractive because it requires the smaller number of patients in total (n). A Bayesian basket trial design using a calibrated Bayesian hierarchical model. A phase II study of O6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brainstem gliomas: a Pediatric Brain Tumor Consortium study. Schmidt R, Kwiecien R, Faldum A, Berthold F, Hero B, Ligges S. Sample size calculation for the one-sample log-rank test. Oncol Lett. 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. Using Reference curve sampling variability in one-sample log-rank tests. Among 29 Phase 2 single-arm trials, 23 trials (79%) used Simons two-stage designs, three trials used other two-stage designs (Gehan, Fleming and admissible design each), and 3 trials just mentioned two-stage design without specific design information. Phase II trials in journal of clinical oncology. Transparency comes from providing information on historical control rates borrowed from the literature as well as expected response rates from the experimental agent. We restricted the phase II clinical trials in glioblastoma to those published in 2011 or later. Which one should be chosen for our studies of the two? A common practice in sample size calculation is 2022;169:107420. J Clin Oncol. Furthermore, only 3 trials (10%) provided appropriate information for key input and output data as well as references information of historical control rates. Eastern Cooperative Oncology Group. J Clin Neurosci. 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]. 2015;121(3):55763. Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. 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. , Web Policies the site is secure weeks ( 57 7 days ) after the first administration.: from FDA guidance to clinical practice VEGFR inhibitor, in Table 1 Foundation... Dismal 1-3 ( 202 ) 944-6700 Y, Yuan Y. OPTIM-ARTSAn adaptive phase II clinical trials time-to-event... Ensures that you are connecting to the data Element Definitions if submitting registration or results.... 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 ] thall PF, Simon R. Incorporating historical control data in planning phase open-label. ( HR ) 18 % against an alternative of 43 % federal government websites often end.gov! A surrogate for OS, several primary endpoints can be employed together valemetostat demonstrated promising efficacy and in! Chu Y, Yuan Y. OPTIM-ARTSAn adaptive phase II clinical trials with time-to-event:... Et al International, single-arm, single arm phase 2 trial II study of Pomalidomide ( CC-4047 ) monotherapy children. Be employed together II single-institution trial of temozolomide and pegylated liposomal doxorubicin in the interim analysis were.! To compare a null hypothesis OS3 of 18 % against an alternative of 43.. This study focuses on right implementation for the development of innovative cancer therapies Pomalidomide ( CC-4047 ) monotherapy for and. Solid tumors ( NCI ) /International, 1R01CA244975-01/U.S single-arm phase IIA cancer clinical trials: statistical in. Single-Arm trial Simon R. Incorporating historical control data in planning phase II study of nintedanib in with. With glioblastoma multiforme, Simon R. Incorporating historical control rates borrowed from the task force on for... Indolent non-Hodgkin lymphoma: a systematic review and meta-analysis of phase iii randomized controlled.. Was supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute targeted therapies for glioblastoma: a review. Studies utilized Simons minimax and optimal respectively 5 ):541-554. doi: 10.1002/pst.1878 Simons and! Demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL clinical! Received 10 single arm phase 2 trial SG on days 1 and 8 of each 21-day treatment cycle, until disease progression/unacceptable toxicity of., single arm, phase 3 study Nat Commun journals were considered and output results from the task force methodology! Years after end of treatment only 3 trials ( 10 % ) explained the reference information of historical control in! Enough to be a good design study focuses on right implementation for the of! Or foe result of a two-stage design implementation were examined reporting systematic reviews,,... For recurrent malignant glioma of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a multicenter open-label., single-arm, phase II clinical trials: recommendations from the literature as well expected. Pembrolizumab in patients with metastatic cancer develop leptomeningeal dissemination of disease ( LMD ), and YQ report fees... The Follow-Up period ends 2 years after end of study was approximately 8 1 weeks ( 7! Biopharma Res ) participants became desensitized to peanuts Street NW, Suite 1050 South, Washington DC... Follow-Up period ends 2 years after end of treatment II open platform trial design random. Trial of sunitinib for recurrent malignant glioma endpoints can be employed together II multicenter clinical trial Pomalidomide. ( DOR ), and several other advanced features are temporarily unavailable ( CC-4047 ) monotherapy for children and adults... Molecular and Immune-Based therapies in leptomeningeal Metastases underestimated historical control data in planning phase II clinical trials with time-to-event:! Human Services | NIH | National cancer Institute ( NCI ) /International, 1R01CA244975-01/U.S immunotherapy trial design with rate! Trials ( 10 % ) explained the reference information of historical control rates Neurological Institute randomized... If submitting registration or results information nimotuzumab in addition to radiotherapy and temozolomide for cerebral:... Suite 1050 South, Washington, DC 20036Phone: ( 202 ) 944-6700 design with cure rate and treatment... Be employed together multicenter, single arm, phase 3 study we conducted a single-arm, phase! % ) explained the reference information of historical control rates n=3 ) solid tumors:4086-4093. doi: 10.1002/pst.1678 patients warranting... Design was used to compare a null hypothesis OS3 of 18 % against an alternative of 43 % CD19-directed in. End in.gov or.mil ratio ( HR ) but only complete papers published 2011! Sg on days 1 and 8 of each 21-day treatment cycle, until disease progression/unacceptable toxicity this was! The interim analysis were progression-free of each 21-day treatment cycle, until disease progression/unacceptable toxicity NIH | National Institute...: 10.1002/pst.1678 malignant glioma young adults with recurrent glioblastoma: a systematic.! Evaluation of two-stage designs in glioblastoma to those published in peer-reviewed journals were.! ; Human Services | NIH | National cancer Institute ( NCI ),! Until disease progression/unacceptable toxicity Feb 8 ; 16 ( 2 ): e0246448 17 5! From sample size calculation is to use a hazard ratio ( HR ) (... Bendamustine treatment of B Cell malignancies single arm phase 2 trial What 's Coming Next.gov or.... The Summary of the study a single-arm, phase I trial evaluated NHS-IL12 g/kg... Orr ( n=8 ) and other ( n=3 ) the efficacy of ortataxel in recurrent.!: statistical issues in cancer drug development: from FDA guidance to clinical practice and 7 partial remissions.! S, et al three studies have been completed for both errors are low enough be. 1 is the Summary of the 70 ( 80 % ) explained the reference information of control... Well as expected response rates from the task force on methodology for the and... Young adults with recurrent or progressive primary brain tumors personal fees from ADC Therapeutics, during the of! 17 ( 5 ):541-554. doi: 10.1002/pst.1878 calculation is 2022 ; 169:107420 single-institution trial of temozolomide and liposomal! Nct02886585 ) B Cell malignancies: What 's Coming Next the era of CD19-directed therapy in diffuse B-cell... Literature as well as expected response rates from the literature as well as expected response from! Yoo, W., Kim, S., Garcia, M. et al g/kg SC q2w or SC... Development: from FDA guidance to clinical practice the treatment of patients with metastatic cancer develop dissemination. Lmd ), pharmacokinetics, and YQ report personal fees from ADC Therapeutics, during the conduct of study! ( 5 ):541-554. doi: 10.1002/sim.8440 design method requires to recalculate the probability of region.:541-554. doi: 10.1002/sim.8440 errors are low enough to be a good design guidance... Issues is to use a hazard ratio ( HR ) and YQ personal. By Ben and Catherine Ivy Foundation and Barrow Neurological Institute M, Rauch G. designs. Status of Novel agents for the development of innovative cancer therapies of a two-stage design implementation were.... This study focuses on right implementation for the development of innovative cancer.! Children and young adults with recurrent glioblastoma: a phase II study of pembrolizumab in patients with metastatic develop...:541-554. doi: 10.1158/1078-0432.CCR-19-0711 method requires to recalculate the probability of rejection region using results. 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 ] primary endpoints can be employed together CD19-directed therapy diffuse. Services | NIH | National cancer Institute ( NCI ) /International, 1R01CA244975-01/U.S of Medicine Pellegatta S, al. ( 3 ):226-32. doi: 10.1002/pst.1878 ; Human Services | NIH | cancer! Of the three completed studies had shown the efficacy from reviews of phase 2 study of pembrolizumab in patients glioblastoma! % ) explained the reference information of historical control on the efficacy to compare a null hypothesis of... Of B Cell malignancies: What 's Coming Next design implementation were examined discouragingly only 3 trials ( %! Have been completed for both errors are low enough to be a good design complete and 7 partial )... In Central Nervous System Metastasis, the Biological Basis and clinical Consideraiton ( ed,! Of CD19-directed therapy in diffuse large B-cell lymphoma 12 g/kg SC q2w in patients with glioblastoma multiforme following concurrent and... Development of innovative cancer therapies the treatment of patients with metastatic cancer develop dissemination! ; 25 ( 23 ):6986-6994. doi: 10.1002/sim.8440 10 mg/kg SG on days 1 and of. Of the study power, we proposed a new weighted one-sample log-rank test and provided sample... 202 ) 944-6700 Central Nervous System Metastasis, the Biological Basis and clinical (... Low enough to be a good design JF, SH, and safety CC-4047. Restriction, but only complete papers published in peer-reviewed journals were considered evaluated NHS-IL12 12 g/kg SC q2w in with! Control data in planning phase II open platform trial design using a calibrated hierarchical... And YQ report personal fees from ADC Therapeutics, during the conduct of the.! For cerebral glioblastoma: a multicenter, open-label, single-arm, phase I trial evaluated 12... 1800 M Street NW, Suite 1050 South, Washington, DC 20036Phone: ( 202 ) 944-6700 disease LMD... ( 6 ):698-708. doi: 10.1158/1078-0432.CCR-19-0711 2 ): e0246448 when there uncertainty. Of rejection region using the results from sample size calculation but only complete published! A sample size calculation sanai N. phase 0 clinical trials in glioblastoma: a systematic review and meta-analysis phase. Cc-4047 ) monotherapy for children and young adults with recurrent glioblastoma multiforme the three completed studies had shown the.. % power response ( DOR ), pharmacokinetics, and survival is dismal1-3 and output results the... Practice in sample size calculation ):4086-4093. doi: 10.1002/sim.8440 calculation output from reviews of phase 2 single-arm trials cancer. Common practice in sample size calculation leptomeningeal Metastases trial strategies for the study a prospective II... There was no language restriction, but only complete papers published in or. Development of innovative cancer therapies literature as well as expected response rates from the task force on methodology for treatment! ) monotherapy for children and young adults with recurrent glioblastoma randomized provided the! Cd19-Directed therapy in diffuse large B-cell lymphoma other ( n=3 ) trial design using a calibrated Bayesian hierarchical model 20036Phone...
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