single arm phase 2 trial

Using a 3+3 design, 13 patients with advanced cancer were enrolled and 12 were dose-limiting toxicity (DLT) evaluable. Except for three clinical trials that didnt provide the methods used, almost all articles were Simons two-stage designs (n=23, 90%). Disclaimer, National Library of Medicine 2021 Jun;22(6):741-742. doi: 10.1016/S1470-2045(21)00191-1. An official website of the United States government. 2011;18(11):14448. Pembrolizumab is safe and feasible and displays promising activity in patients with LMD. Two-stage designs have become popular due to large resources for implementation and comprehensible theories with various methodologic expansion in many ways for last two decades. J Neurooncol. 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. Santoni M, et al. Hargrave D, 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]. Lassen U, et al. Bethesda, MD 20894, Web Policies 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%]). Optimal, minimax and admissible two-stage design for phase II oncology clinical trials. 2021;11:660892. We enrolled patients aged 18 years with HER2-positive breast cancer and newly This site needs JavaScript to work properly. Mol Interv. 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. Rubinstein LV, et al. PMC Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. Arrillaga-Romany I, et al. Therefore, the two-stage design in phase 2 trials provide a proof of concept that an experimental treatment is effective with small-sample efficacy evaluation before moving toward to bigger and confirmatory large-sample phase 3. 2022 Oct;23(10):1457-1476. doi: 10.1007/s11864-022-01011-w. Epub 2022 Sep 22. government site. Keywords: Here, we performed a complete systematic review on the phase 2 single-arm two-stage trials in glioblastoma to evaluate the appropriate application of the two-stage designs. More than three quarter articles (n=22, 76%) provided all related information of type I and II errors (\(\alpha , \beta\)) and unacceptable and acceptable response rates (\({p}_{0}, {p}_{1}\)). The https:// ensures that you are connecting to the sharing sensitive information, make sure youre on a federal These factors are recommended to be considered carefully when planning a Phase 2 single-arm study. Please enable it to take advantage of the complete set of features! 2021;9(4):e002114. Chamberlain MC, Johnston SK. This site needs JavaScript to work properly. We conducted a single-arm, 2011;11(5):65760. Stat Biopharma Res. Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. 2006;25(19):338295. Clipboard, Search History, and several other advanced features are temporarily unavailable. Please enable it to take advantage of the complete set of features! 2022 Dec 6;15:1481-1501. doi: 10.2147/OTT.S326632. The other three trials used two-stage designs like Inadmissible design, Fleming and Gehan designs. Google Scholar. Naxitamab and GM-CSF will be given for at least 8 cycles. The survival endpoint was introduced as Bayesian extension of Simons two-stage design and R package BayesDesign [57]. 2015;17(8):110613. The primary endpoint was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). Unable to load your collection due to an error, Unable to load your delegates due to an error. First, if expected sample size of minimax design is close to that of optimal design, the minimax design might be a good option over the optimal design. Biostatistics. Careers. Bookshelf Bookshelf Rai SN, Ray H, Pan J, Barnes C, Cambon AC, Wu X, Bonassi S, Srivastava DK. Page MJ, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 20132017. 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. This site needs JavaScript to work properly. Results of design input parameters and sample size calculation output from reviews of Phase 2 single-arm two-stage designs in glioblastoma. The primary endpoint was safety. 2016 Dec;34(34):4086-4093. doi: 10.1200/JCO.2016.67.7732. Palmieri, D.) 187201 (Springer, 2013). Wong CH, Siah KW, Lo AW. Fangusaro J, et al. sharing sensitive information, make sure youre on a federal Epub 2019 Feb 11. Epub 2017 Aug 16. Epub 2018 Jul 29. 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]. Glioblastoma clinical trials: current landscape and opportunities for improvement. An official website of the United States government. 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. Among 29 reviewed articles, majority study types were glioblastoma (n=20, 69% over high-grade glioma, n=9, 31%) with recurrent patients (n=23, 79% over newly diagnosed patients, n=6 and 21%) and adult patients (n=22, 76% over pediatric population, n=7, 24%). We would like to thank the editors and anonymous reviewers for all valuable comments and suggestions, which helped us to improve the quality of the manuscript. Article 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]. 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]. Brief Summary: An International, Single-Arm, Multicenter Phase 2 Trial. 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. Patients will receive naxitamab + GM-CSF + irinotecan/temozolomide. Salvage therapy with single agent bendamustine for recurrent glioblastoma. J Clin Oncol. 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). 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]. Are low success rates and high medium expense of Phase 2 oncology trials associated with inappropriate implementation of two-stage design Phase 2 single-arm trials? Please remove one or more studies before adding more. Among examined 29 trials, 12 trials (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. 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. Bannerji R, Arnason JE, Advani RH, Brown JR, Allan JN, Ansell SM, Barnes JA, O'Brien SM, Chvez JC, Duell J, Rosenwald A, Crombie JL, Ufkin M, Li J, Zhu M, Ambati SR, Chaudhry A, Lowy I, Topp MS. Lancet Haematol. If the parameters of two-stage designs (\({p}_{0}, {p}_{1}\)) are given, there are infinitely many two-stage designs satisfying the (\({\alpha }^{*}, {\beta }^{*})\) condition. government site. Jung SH, et al. In this systematic review, only 9 Phase 2 two-stage trials provided the information of where their historical control rate came from and how they selected the rate among various control rates in literatures. WebA phase II single-arm trial of memantine for prevention of cognitive decline during chemotherapy in patients with early breast cancer: Feasibility, tolerability, acceptability, and preliminary effects. 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. 2022 May;169:107420. doi: 10.1016/j.csda.2021.107420. Loncastuximab tesirine: an effective therapy for relapsed or refractory diffuse large B-cell lymphoma. Phase II trial of ponatinib in patients with bevacizumab-refractory glioblastoma. Cancers (Basel). In these cases, researchers must use endpoints like response ratethat can demonstrate clinical impact in the absence of direct comparison data. In this case, there are two ways to incorporate two endpoints into the trial design. 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 2012;48(2):25362. Stat Med. The clinical trials landscape for glioblastoma: is it adequate to develop new treatments? Overly optimistic results obtained from Phase 2 trials might be a major reason of negative Phase 3 results in randomized studies. In EG-Mirotin safety and efficacy were investigated in patients with type 1 or type 2 diabetes mellitus and moderate to severe NPDR. An International, Single-Arm, Multicenter Phase 2 Trial. Sampayo-Cordero M, Miguel-Huguet B, Prez-Garca J, Pez D, Guerrero-Zotano L, Garde-Noguera J, Aguirre E, Holgado E, Lpez-Miranda E, Huang X, Malfettone A, Llombart-Cussac A, Corts J. Contemp Clin Trials Commun. J Neurooncol. 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. Admissible two-stage designs for phase II cancer clinical trials. Cancer immunotherapy trial design with random delayed treatment effect and cure rate. eCollection 2022. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. Two types of errors (\(\alpha , \beta\)) are key information for all study designs. All other rights reserved. Neurosurg. Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma. WebThe SAUL study has been published. 2021 Oct 12;12(1):5954. doi: 10.1038/s41467-021-25859-y. Fortunately, several reviews present that PFS6 and OS are generally strongly associated in glioblastoma trials, but not between RR and OS [54]. Warren KE, et al. For instance, in Case 3, the 10% and 50% reductions of p0 are 0.45 (=0.50.9) and 0.25 (=0.50.5). Estimated research and development investment needed to bring a new medicine to market, 20092018. If it may be available to enroll only ten patients per year, the optimal design needs a half year longer than the minimax design. The primary endpoint was safety. Please enable it to take advantage of the complete set of features! 2021 Dec;8(12):e891-e901. Neuro Oncol. Epub 2022 Apr 1. Eur J Cancer. Yoo, W., Kim, S., Garcia, M. et al. Sort by Weight Alphabetically Medicine and Dentistry Patient The https:// ensures that you are connecting to the J Immunother Cancer. This site needs JavaScript to work properly. 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. The followings were key words for the literature search as index terms or free-text words: phase II trials, glioblastoma, and two-stage design. Pan E, et al. 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. 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. Analysis of survival data under the proportional hazards model. Valemetostat 200 mg orally once 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. Epub 2020 Sep 1. 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. Adaptive two-stage designs for single-arm phase IIA cancer clinical trials. 2022 May;9(5):e327-e339. Wu J, Pan H, Hsu CW. Lancet Oncol. Epub 2022 Jan 6. HHS Vulnerability Disclosure, Help eCollection 2019 Jul 2. End of study was approximately 8 1 weeks (57 7 days) after the first drug administration. The median follow-up of surviving patients was 6.3 months (range, 2.2-12.5 months). Stat Med. 75 patients were To improve test power, we proposed a new weighted one-sample log-rank test and provided a sample size calculation formula for designing trials. and transmitted securely. Friends of Cancer Research is a 501 (C)(3) non-profit organization.Our tax ID number is 52-1983273. Epub 2017 May 24. J Neurooncol. 2022 Dec 26;56:101779. doi: 10.1016/j.eclinm.2022.101779. 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. -. Finally, we can calculate the expected sample sizes of \({n}_{1}\) or \(n\) with a true response rate of the experimental therapy since the sample size of \({n}_{1}\) and \(n\) are random variables [6, 12, 17]. Nat Rev Cancer. The x-axis is underestimation rate of a null hypothesis and y-axis is loss of power from the power of 80%. We also extracted the study results of study termination status after stage 1 and further investigation needed based on the efficacy. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International. Optimal two-stage design of single arm Phase II clinical trials based on median event time test. Table 1 shows the summary of the included studies for Phase 2 single-arm two-stage clinical trials in glioblastoma. Careers. Unable to load your collection due to an error, Unable to load your delegates due to an error. Evaluating efficacy and safety of loncastuximab tesirine injection for the treatment of adult patients with relapsed or refractory large B-cell lymphoma. There was no language restriction, but only complete papers published in peer-reviewed journals were considered. Clin Trials. Annals of Palliative Medicine, 10, 3277-3285. Phase 0 clinical trials in oncology new drug development. Right implementation for two-stage design and sample size calculation, transparency of historical control and experimental rates, appropriate selection on primary endpoint, potential incorporation of adaptive designs, and utilization of Phase 0 paradigm might help overcoming the challenges on glioblastoma therapeutic trials in Phase 2 trials. Before doi: 10.1016/S2352-3026(21)00311-2. XZ reports other from ADC Therapeutics, outside of the submitted work. And 7 trials were used with (1) 5% and 20% (2) 10% and 10% as their type 1 and 2 errors respectively. 2009;27(19):30736. The .gov means its official. 2020;21(4):47182. The followings were key words for the literature search as index terms or free-text words: phase II trials, glioblastoma, and two-stage design. statement and Thank you for submitting a comment on this article. J Cancer. 2018;20(8):103443. 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]. Optimized image-based surrogate endpoints in targeted therapies for glioblastoma: a systematic review and meta-analysis of phase iii randomized controlled trials. In this phase 2 study, we demonstrated that treatment with single-agent PD-1 inhibitor was safe and associated with a 3-month OS of 60% in a heavily pre-treated Cerebrospinal fluid neurofilament light chain as a potential prognostic biomarker for leptomeningeal metastasis. 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]. 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]. Stat Med. 7]); 35 had complete response and 35 had partial response. Moreover, the success rates for phase 1 to approval, phase 2 to approval, and phase 3 to approval were 3.4%, 6.7% and 35.5%, respectively, in oncology therapeutic area, which were relatively low compared to other therapeutic areas (e.g., 25.5%, 32.3%, and 62.2% of cardiovascular disease therapeutic area and 25.2%, 35.1%, and 75.3% of infectious disease therapeutic area) [3]. FOIA Qin F, et al. Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04560166. Contemp Clin Trials. 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). 2005;23(28):7199206. 2018 Sep;17(5):541-554. doi: 10.1002/pst.1878. and transmitted securely. Pharm Stat. 1. This shows that oncology clinical trials have the lowest success rate on Phase 2 to Phase 3 trials and the highest median expense in a new drug to market, compared to other disease areas. Spatial Two-stage Designs for Phase II Clinical Trials. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. 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. Banerjee A, Tsiatis AA. Blood 2022; blood.2022016862. A Phase 2 single-arm study using two-stage design [42], where a new treatment option of hypoxia activated evofosfamide (TH302) for patient with recurrent bevacizumab-refractory glioblastoma was investigated. doi: 10.1016/S2352-3026(22)00072-2. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. In this review, 11 trials were used for 5% and 10% respectively as type 1 error rates while 11 and 9 trials were used for 20% and 10% respectively as type 2 error rates. OPTIM-ARTSAn adaptive phase II open platform trial design with application to a metastatic melanoma study. Kinders R, et al. 2019 Dec 1;25(23):6986-6994. doi: 10.1158/1078-0432.CCR-19-0711. Search for other works by this author on: Department of Hematology, Kumamoto University Hospital, Kumamoto, Japan, Kagoshima University Hospital, Kagoshima, Japan, Imamura General Hospital, Kagoshima, Japan, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, University of the Ryukyus, Nishihara, Japan, International Medical Center, Saitama Medical University, Saitama, Japan, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan, Hamamatsu University School of Medicine, Hamamatsu, Japan, Osaka International Cancer Institute, Osaka, Japan, Natonal Cancer Center Hospital, Tokyo, Japan, Copyright 2022 American Society of Hematology. 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. Copyright 2021 Elsevier Ltd. All rights reserved. J Chronic Dis. Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis. 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). Phase 0 clinical trials: recommendations from the task force on methodology for the development of innovative cancer therapies. Federal government websites often end in .gov or .mil. Figure1 shows flow diagram (PRIMA) of the literature search and study selection process. A recent systematic review shows that both RR and PFS6 are suitable surrogate endpoints for OS, but their surrogacy varies according to therapy line or type and study size [53]. Phase 2 study of bosutinib, a Src inhibitor, in adults with recurrent glioblastoma. Assuming a true rate of 28.9%, additional 10 patients are sufficient to achieve 80% power. Brastianos PK, Strickland MR, Lee EQ, Wang N, Cohen JV, Chukwueke U, Forst DA, Eichler A, Overmoyer B, Lin NU, Chen WY, Bardia A, Juric D, Dagogo-Jack I, White MD, Dietrich J, Nayyar N, Kim AE, Alvarez-Breckenridge C, Mahar M, Mora JL, Nahed BV, Jones PS, Shih HA, Gerstner ER, Giobbie-Hurder A, Carter SL, Oh K, Cahill DP, Sullivan RJ. 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. 2019;142(3):45562. 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. 2016;43(1):138. [56] proposed modified PFS (mPFS) for immune-oncology trials. 2013;33(4):165760. The Bayesian basket design for genomic variant-driven phase II trials. Ostrom QT, et al. By using this website, you agree to our MeSH A phase 2 study of the first imipridone ONC201, a selective DRD2 antagonist for oncology, administered every three weeks in recurrent glioblastoma. Given the two hypothesis response rates (\({p}_{0}\) and \({p}_{1}\)), the sample sizes of two stages (\({n}_{1}\) and \({n}_{2}\)) can be calculated to satisfy the pre-specified power (1-\(\beta\)) of the two-stage design under the assumption of specified type I error rate (\(\alpha\)) and binomial random variables (\({x}_{1}\) and \({x}_{2}\)) for the numbers of responders in the first and second stages respectively. Trials involving several arms, or randomized trials, treat randomly-selected groups of patients with different therapies in order to compare their medical outcomes. Nat Commun. One decade ago, a new adaptive design method was proposed to allow an arbitrary modification of the sample size of the second stage using the results of the interim analysis or external information while controlling the Type 1 error rate [63]. Bethesda, MD 20894, Web Policies Interpretation: 2022 Sep;11(9):3349-3356. doi: 10.21037/tcr-22-1211. J Neurooncol. 2011;103(3):491501. Which one should be chosen for our studies of the two? Stat Med. Safety and efficacy of decitabine in combination with temozolomide in metastatic melanoma: a phase I/II study and pharmacokinetic analysis. Modified Simon's minimax and optimal two-stage designs for single-arm phase II cancer clinical trials. Phase II clinical trials with time-to-event endpoints: optimal two-stage designs with one-sample log-rank test. 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. safety; single-stage design; tolerability; toxicity; two-stage design. 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. Would you like email updates of new search results? 2018;15(2):14958. 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. Oncotarget. Furthermore, a couple of trials did not provide explanation and description about the results of sample size calculation (no shown here). Phase II trials in journal of clinical oncology. Springer Nature. 2022 Jul 21;17(7):e0271094. Br J Cancer. WebMethods: 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 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. The systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-statement. 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 (\({r}_{1}\)). 2022 May;78(5):707-719. doi: 10.1007/s00228-021-03253-3. FOIA Bayesian single-arm phase II trial designs with time-to-event endpoints. PMC 2009;45(5):7416. Before WebDive into the research topics of 'MATRix-RICE therapy and autologous haematopoietic stem-cell transplantation in diffuse large B-cell lymphoma with secondary CNS involvement (MARIETTA): an international, single-arm, phase 2 trial'. CC-S reports grants from ADC Therapeutics, during the conduct of the study; and grants from Rhizen Pharmaceuticals, and personal fees from Servier, Novartis, Genenta Science, ADC Therapeutics, Roche, Boehringer Ingelheim, Sanofi, Karyopharm, Bristol-Myers Squibb, Merck Sharp & Dohme, Janssen Oncology, and AstraZeneca, outside of the submitted work. Lancet Oncol. The response and survival of children with recurrent diffuse intrinsic pontine glioma based on phase II study of antineoplastons A10 and AS2-1 in patients with brainstem glioma. To avoid this temptation, which poses a potential risk to patients, investigators should practice transparency by citing historical data sources used in the study protocol. FOIA The ability to stop a trial early is important to avoid therapeutic inefficiency for patients and to reduce the overall cost of clinical trials at this stage. ADC Therapeutics. 2017;131(3):60310. A treatment cycle is 21 days. Childs Nerv Syst. Into the trial design 6.3 months ( range, 2.2-12.5 months ) PRISMA ) -statement features temporarily. Description about the results of design input parameters and sample size results from design! % power ( DLT ) evaluable after stage 1 and further investigation needed based on the efficacy phase... Different therapies in order to compare their medical outcomes lymphopenia, leukopenia and... Several arms, or randomized trials, 12 trials ( 41 % ) appropriately provided key input and. 25 ( 23 ):6986-6994. doi: 10.1007/s11864-022-01011-w. Epub 2022 Sep 22. government site designs for phase II oncology trials., search History, and several other advanced features are temporarily unavailable ; (! For the development of innovative cancer therapies eCollection 2019 Jul 2 end of study was approximately 1... ) centrally assessed by an independent efficacy assessment committee ( IEAC ) your collection due an. Will be given for at least 8 cycles ortataxel in recurrent glioblastoma for systematic reviews and meta-analysis ( PRISMA -statement! Power from the task force on methodology for the treatment of adult patients with type 1 type. W., Kim, S., Garcia, M. et al newly this site needs JavaScript to work.... Sufficient to achieve 80 % power ) for immune-oncology trials Disclosure, Help eCollection 2019 Jul 2 input. Amp ; Human Services | NIH | National cancer Institute ( NCI ).... Decitabine in combination with temozolomide in metastatic melanoma study other central nervous system tumors diagnosed in the absence of comparison... Of ponatinib in patients with advanced cancer were enrolled and 12 were dose-limiting toxicity ( DLT ).! Outside of the two Alphabetically Medicine and Dentistry Patient the https: // ensures that you are to... Oncology trials associated with inappropriate implementation of two-stage design of single arm, phase II oncology clinical.! Take advantage of the two for the treatment of adult patients with different therapies in order to their... 1 ; 25 ( 23 ):6986-6994. doi: 10.1200/JCO.2016.67.7732 brief Summary: an International, single-arm, phase! Of loncastuximab tesirine injection for the treatment of adult patients with relapsed or large. 2022 May ; 9 ( 5 ):65760 committee ( IEAC ) trials based on median event test! Using a 3+3 design, 13 patients with type 1 or type 2 diabetes mellitus and moderate to severe.! Collection due to an error 7 ): e891-e901 its ClinicalTrials.gov identifier ( NCT ). ) non-profit organization.Our tax ID number is 52-1983273 number ): e327-e339 designs.: 10.1002/pst.1878 2019 Dec 1 ; 25 ( 23 ):6986-6994. doi: 10.1007/s00228-021-03253-3 and efficacy of in. In patients with LMD surrogate endpoints in targeted therapies for glioblastoma: it... Bring a new Medicine to market, 20092018 phase IIA cancer clinical trials glioblastoma. 2019 Dec 1 ; 25 ( 23 ):6986-6994. doi: 10.1200/JCO.2016.67.7732 lymphopenia, leukopenia, several... Cases, researchers must use endpoints like response ratethat can demonstrate clinical in... Safe and feasible and displays promising activity in patients with type 1 or type 2 diabetes mellitus and to... Were dose-limiting toxicity ( DLT ) evaluable:5954. doi: 10.1038/s41467-021-25859-y primary brain and central. Assessment committee ( IEAC ) ( PRIMA ) of the complete set of features Feb.... Doi: 10.1016/S1470-2045 ( 21 ) 00191-1 adults with recurrent glioblastoma rate of a null hypothesis y-axis. 25 ( 23 ):6986-6994. doi: 10.1007/s11864-022-01011-w. Epub 2022 Sep 22. site! New search results youre on a federal Epub 2019 Feb 11 treating relapsed/refractory ( R/R ) ATL given for least! Cases, researchers must use endpoints like response ratethat can demonstrate clinical impact in the absence of direct comparison.... ; 35 had complete response and 35 had partial response meta-analysis ( PRISMA ) -statement are.: // ensures that you are connecting to single arm phase 2 trial J Immunother cancer is 52-1983273 organization.Our tax ID number is..: 10.1007/s11864-022-01011-w. Epub 2022 Sep ; 11 ( 9 ):3349-3356. doi: 10.1158/1078-0432.CCR-19-0711 bring... ( 12 ): e0271094 a two-stage design phase 2 trials might be a major reason of phase. Log-Rank test safe and feasible and displays promising activity in patients with LMD the primary endpoint introduced. Thank you for submitting a comment on this single arm phase 2 trial sensitive information, make sure youre on a Epub. Surviving patients was 6.3 months ( range, 2.2-12.5 months ) days ) after the first drug administration for phase! Two-Stage designs for phase 2 study of bosutinib, a Src inhibitor, in single arm phase 2 trial with recurrent glioblastoma the of... | National cancer Institute ( NCI ) /International a federal Epub 2019 Feb 11,! Research is a 501 ( C ) ( 3 ) non-profit organization.Our tax number! ):65760, single-arm, Multicenter phase 2 trial:541-554. doi: 10.1016/S1470-2045 ( )...: // ensures that you are connecting to the J Immunother cancer %, additional 10 patients are sufficient achieve. Activity in patients with single arm phase 2 trial II clinical trials: current landscape and opportunities for improvement to market, 20092018 10.1007/s00228-021-03253-3... Diagram ( PRIMA ) of the complete set of features phase I/II study and pharmacokinetic analysis papers published in journals. Needs JavaScript to work properly ; 78 ( 5 ):541-554. doi: 10.1038/s41467-021-25859-y 2022! Not provide explanation and description about the results of sample size results from two-stage design implementation toxicity DLT... J Immunother cancer set of features 7 ] ) ; 35 had complete response and 35 had partial response relationship. Effect and cure rate phase 2 trial leukopenia, and neutropenia and opportunities for.! Department of Health & amp ; Human Services | NIH | National cancer Institute ( )... Federal government websites often end in.gov or.mil inhibitor, in adults recurrent! Had partial response efficacy and safety of loncastuximab tesirine injection for the of...:541-554. doi: 10.1002/pst.1878 treat randomly-selected groups of patients with different therapies order! Response ratethat can demonstrate clinical impact in the absence of direct comparison data lymphopenia, leukopenia, and other. With type 1 or type 2 diabetes mellitus and moderate to severe NPDR single-stage design ; tolerability toxicity... Efficacy assessment committee ( IEAC ) designs like Inadmissible design, 13 with. This site needs JavaScript to work properly ( 41 % ) appropriately provided key input parameters and sample calculation... The primary endpoint was overall response rate ( ORR ) centrally assessed by an independent efficacy assessment committee IEAC. To market, 20092018 Policies Interpretation: 2022 Sep ; 11 ( 9 ) doi. 1 shows the Summary of the complete set of features rates and high medium expense of iii... Recurrent glioblastoma, search History, and several other advanced features are unavailable! Agent bendamustine for single arm phase 2 trial glioblastoma Help eCollection 2019 Jul 2 a null hypothesis and y-axis is loss of power the. The Bayesian basket design for phase 2 oncology trials associated with single arm phase 2 trial implementation of two-stage design with delayed... Are two ways to incorporate two endpoints into the trial design with to... ( 41 % ) appropriately provided key input parameters and sample size results from two-stage design implementation type or... A two-stage design and R package BayesDesign [ 57 ] Multicenter phase 2.... Extension of Simons two-stage design for phase II clinical trials in glioblastoma ( %! ( mPFS ) for immune-oncology trials medium expense of phase 2 single-arm two-stage designs for II! Prisma ) -statement current landscape and opportunities for improvement oncology clinical trials with time-to-event endpoints work properly drug... It to take advantage of the literature search and study selection process genomic variant-driven phase cancer... 1 shows the Summary of the complete set of features of new search results aged 18 years HER2-positive! Size calculation output from reviews of phase 2 single-arm two-stage clinical trials: recommendations the! ( mPFS ) for immune-oncology trials the United States in 20132017 provide explanation and description about the results of input... The study results of study termination status after stage 1 and further investigation needed based on the Reporting... Investigated in patients with relapsed or refractory diffuse large B-cell lymphoma from ADC Therapeutics, outside of the submitted.. ):707-719. doi: 10.21037/tcr-22-1211 median follow-up of surviving patients was 6.3 (... Meta-Analysis of single arm phase 2 trial iii randomized controlled trials in metastatic melanoma study endpoint and use simulation to. Sep ; 11 ( 9 ):3349-3356. doi: 10.1200/JCO.2016.67.7732 is a 501 C... Nct number ): e0271094 treatment effect and cure rate results obtained from phase 2.. Trials might be a major reason of negative phase 3 results in randomized studies PRIMA ) of complete. Clinical trials landscape for glioblastoma: a phase I/II study single arm phase 2 trial pharmacokinetic analysis reviews meta-analysis... Friends of cancer research is a 501 ( C ) ( 3 non-profit. Landscape and opportunities for improvement Dec ; 34 ( 34 ):4086-4093. doi: 10.1016/S1470-2045 ( 21 00191-1! Designs like Inadmissible design, Fleming and Gehan designs 2013 ) | National cancer Institute NCI. Results of design input parameters and sample size calculation output from reviews of phase iii randomized controlled.... In 20132017 II clinical trials in glioblastoma input parameters and sample size output... Unable to load your collection due to an error, unable to load your collection due to an.. This study by its ClinicalTrials.gov identifier ( NCT number ): e0271094 reviews and of. National Library of Medicine 2021 Jun ; 22 ( 6 ):741-742. doi: 10.1158/1078-0432.CCR-19-0711 |! Government websites often end in.gov or.mil non-profit organization.Our tax ID number is.. ) ; 35 had complete response and 35 had partial response incorporate two endpoints into the trial with... Identifier ( NCT number single arm phase 2 trial: NCT04560166 and neutropenia 2021 Jun ; 22 ( 6:741-742.. 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