We conducted the prospective, open-label, single-arm, phase 2 TUXEDO-1 trial. The sample size calculation for the two-stage designs is determined based on the historical control rate and difference between the two rates (\({p}_{0}, {p}_{1}\)). 2019 Mar;20(3):371-382. doi: 10.1016/S1470-2045(18)30812-X. Temozolomide (TMZ) was mostly used for combination therapeutic drugs (n=7 with pegylated liposomal doxorubicin (PLD), O6-benzylguanine (O6B), irinotecan (IRI), decitabine (DAC), Dendritic (DEN), Nintedanib (NIN), and Atorvastatin (ATO)) while Bevacizumab (BEV) was second mostly used for combination drugs (n=3 with temsirolimus (TEM), Ponatinib (PON), and Evofosfamide (EVO)). BSK reports grants from ADC Therapeutics, during the conduct of the study; and personal fees from Seattle Genetics and Genentech, outside of the submitted work. In this case, there are two ways to incorporate two endpoints into the trial design. Bookshelf Please enable it to take advantage of the complete set of features! Optimized image-based surrogate endpoints in targeted therapies for glioblastoma: a systematic review and meta-analysis of phase iii randomized controlled trials. How low levels for both errors are low enough to be a good design? FOIA 2017;8(45):79298304. Trials involving several arms, or randomized The primary endpoint was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). Evaluating efficacy and safety of loncastuximab tesirine injection for the treatment of adult patients with relapsed or refractory large B-cell lymphoma. J Neurooncol. Altwairgi AK, et al. Bethesda, MD 20894, Web Policies Lin Y, Shih WJ. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial Summary 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]. Suppose both RR and PFS6 are considered primary endpoints. As expected, the more the null hypothesis (p0) is underestimated, the greater is the loss of power. Before Pellegatta S, et al. Loncastuximab tesirine has substantial single-agent antitumour activity and produces durable responses with an acceptable safety profile, potentially offering a new therapeutic option for heavily pretreated patients with relapsed or refractory DLBCL. By using this website, you agree to our Sci Rep. 2021;11(1):2306. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. 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. WebZhao, Y., Zhang, X., Jin, C.X., et al. 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. A common practice in sample size calculation is to assume that the event time in the new treatment follows exponential distribution. 2015 May-Jun;14(3):226-32. doi: 10.1002/pst.1678. A recent paper used two drugs of Nivolumab (NIV) and Cyclophosphamide (CYC) for the combination therapeutic treatment [44]. Reference curve sampling variability in one-sample log-rank tests. Kaley TJ, et al. Adult T-cell leukemia/lymphoma (ATL) is an aggressive non-Hodgkin lymphoma with poor prognosis and few treatment options for patients with relapsed, recurrent, or refractory disease. A phase II single-arm study of irinotecan in combination with temozolomide (TEMIRI) in children with newly diagnosed high grade glioma: a joint ITCC and SIOPE-brain tumour study. 2018;20(8):103443. Phase 0 clinical trials in cancer drug development: from FDA guidance to clinical practice. 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. Springer Nature. The .gov means its official. Cite this article. -, Wang, N., Bertalan, M. S. & Brastianos, P. K. Leptomeningeal metastasis from systemic cancer: review and update on management. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. Patients will receive up to 18 IT cycles after enrollment. Ott PA, Elez E, Hiret S, Kim DW, Morosky A, Saraf S, Piperdi B, Mehnert JM. Pharm Stat. End of study was approximately 8 1 weeks (57 7 days) after the first drug administration. 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. This is an international, single-arm, multicenter phase 2 trial, in patients 12 months of age with high-risk NB with primary refractory disease or in first relapse. Unable to load your collection due to an error, Unable to load your delegates due to an error. J Neurooncol. 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. Lassen U, et al. Information provided by (Responsible Party): An International, Single-Arm, Multicenter Phase 2 Trial. Comparison of error rates in single-arm versus randomized phase II cancer clinical trials. Unable to load your collection due to an error, Unable to load your delegates due to an error. Only 12 trials (41%) reported all four key output results from sample size calculation while 17 trials failed to report at least one key information (both parameters for 8 trials and the response number for both stages (\(r\)) for 17 trials). 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 Schmidt R, Faldum A, Kwiecien R. Adaptive designs for the one-sample log-rank test. But interestingly almost 60% of studies (17/29, 59%) failed to provide at least one key output results of sample size calculation such as the number of samples of first stage and both stages (\({n}_{1}, n\)) and the treatment rejection numbers of the first stage and both stages (\({r}_{1}, r\)). Loncastuximab tesirine: an effective therapy for relapsed or refractory diffuse large B-cell lymphoma. Gehan EA. (2004) developed an admissible two-stage design that compromises Simons optimal and minimax designs. eCollection 2023 Feb. Tannoury M, Garnier D, Susin SA, Bauvois B. Treatment-emergent adverse events (TEAEs) were manageable. We identified a total of 81 articles based on online search using Two-stage Phase II trials in glioblastoma. Page MJ, et al. Phase 0 clinical trials in oncology new drug development. A treatment cycle is 21 days. 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. Before in Central Nervous System Metastasis, the Biological Basis and Clinical Consideraiton (ed. 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 A common practice in sample size calculation is 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]. Epub 2022 Jan 6. Warren KE, et al. Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. Racine-Poon A, et al. 2015;34(16):240316. Keywords: Biometrics. 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. 2022 Dec 6;15:1481-1501. doi: 10.2147/OTT.S326632. 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. 2020 Aug;26(8):1309. doi: 10.1038/s41591-020-0978-1. TACE-HAIC Plus Lenvatinib for Patients With Unresectable HCC: an Open-label, Single-arm, Phase 2 Trial (Thalen) The safety and scientific validity of this study The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Phase 0 clinical trials: recommendations from the task force on methodology for the development of innovative cancer therapies. Wang Z-X, et al. Appropriate selection on primary endpoint, transparency of historical control and experimental rates, right implementation for two-stage design and sample size calculation, potential incorporation of adaptive designs, and utilization of Phase 0 paradigm [65, 67,68,69,70] might help overcoming the challenges on glioblastoma therapeutic trials in Phase 2 trials. Fleming TR. Epub 2022 Jan 21. 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]. 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, Single-arm studies have been traditionally used in Phase II oncology clinical trials. Would you like email updates of new search results? Bookshelf An official website of the United States government. Stat Med. Estimation of clinical trial success rates and related parameters. 75 patients were MS reports grants from ADC Therapeutics, during the conduct of the study; and personal fees from Amgen and Celgene, outside of the submitted work. Br J Cancer. The clinical trials landscape for glioblastoma: is it adequate to develop new treatments? Epub 2017 Aug 16. 2001 May;32(2):155-62. doi: 10.1016/s0169-5002(00)00220-8. 2020 Jul;21(7):978-988. doi: 10.1016/S1470-2045(20)30225-4. View this study on Beta.ClinicalTrials.gov, Genetic and Rare Diseases Information Center, U.S. Department of Health and Human Services, The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. 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. 2004;23(4):5619. WebThe trial ended after accrual completion; the database lock was Dec 31, 2019. 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]. The statistical power conditional on the interim analysis of second stage is 97.3% for the true rate of 28.9%, which is far beyond the originally pre-specified 80% of power. Stat Med. Comput Stat Data Anal. 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. A phase II trial of oral gimatecan for recurrent glioblastoma. [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. Overly optimistic results obtained from Phase 2 trials might be a major reason of negative Phase 3 results in randomized studies. Glioblastoma clinical trials: current landscape and opportunities for improvement. 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. Norden AD, et al. 2019 Dec 1;25(23):6986-6994. doi: 10.1158/1078-0432.CCR-19-0711. Exploration of modified progression-free survival as a novel surrogate endpoint for overall survival in immuno-oncology trials. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. J Neurooncol. Ivy Brain Tumor Center, Department of Translational Neuroscience, Barrow Neurological Institute, Phoenix, AZ, 85013, USA, Karmanos Cancer Institute, Department of Oncology, School of Medicine, Wayne State University, Detroit, MI, 48201, USA, Department of Radiation Oncology, Barrow Neurological Institute, Phoenix, AZ, 85013, USA, You can also search for this author in 2013;111(2):20512. Anand S, et al. Epub 2019 Nov 26. Clin Trials. FOIA This popularity is because the two-stage design in Phase 2 single-arm trials allows for early trial termination for ineffective experimental therapies (i.e., futility). Schmidt R, Kwiecien R, Faldum A, Berthold F, Hero B, Ligges S. Sample size calculation for the one-sample log-rank test. 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]. 2019;20(2):27386. Publisher Correction: Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. Among examined 29 trials, 12 trials (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. Cookies policy. Santoni M, et al. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. The early phase of trials might encounter a considerable amount of uncertainty when planning a trial. Clipboard, Search History, and several other advanced features are temporarily unavailable. Stat Med. mPFS does not include the events of disease progression but include the events of death within 3months after randomization. Serious adverse events were reported in 57 (39%) of 145 patients. 1982;38(1):14351. 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 (\({r}_{1}\)). In this manner, the two-stage designs allow stopping of a futile trial early. 2011;18(11):14448. 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]. Clin Cancer Res. Neuro Oncol. Refining Therapy in Patients with HER2-Positive Breast Cancer with Central Nervous System Metastasis. Simons optimal design for a one-sided significance level of 0.05 and a power of 0.80 includes 11 patients in the first stage. 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. government site. Clipboard, Search History, and several other advanced features are temporarily unavailable. Our simulation study showed that the proposed log-rank test performs well and is robust of misspecified weight and the sample size calculation formula also performs well. Keywords: Therapeutic Antibodies in Cancer Treatment in the UK. 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. 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. Qin F, et al. Tang H, et al. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). 2020;21(4):47182. An increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal1-3. Single-arm phase II trial design under parametric cure models. Tawbi HA, et al. Vanderbeek AM, et al. 2018 Sep;17(5):541-554. doi: 10.1002/pst.1878. 1996 Oct;74(8):1317-20. doi: 10.1038/bjc.1996.537. J Clin Oncol. Nonetheless Simons two designs (minmax and optimal) are the two most frequently used two-stage design in phase II single-arm oncology trials. None Created on Jan 16, 2023 Publication details Reviews All publications My publications Add new publication Import from PubMed More Before HHS Vulnerability Disclosure, Help Re-formulating Gehan's design as a flexible two-stage single-arm trial. Estimated research and development investment needed to bring a new medicine to market, 20092018. Epub 2022 Aug 10. Wu X, Wu C, Liu F, Zhou H, Chen C. A generalized framework of optimal two-stage designs for exploratory basket trials. Table 1 shows the summary of the included studies for Phase 2 single-arm two-stage clinical trials in glioblastoma. HHS Vulnerability Disclosure, Help statement and Patients received 200 mg of pembrolizumab intravenously every 3 weeks until definitive progression or unacceptable toxicity. Sharma M, et al. Invest New Drugs. J Neurooncol. Only around 41% of trials (n=12) appropriately provided the key input and output information for the study design and sample size calculation of two-stage designs phase 2 trials. 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. 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]. doi: 10.1371/journal.pone.0246448. Design issues of randomized phase II trials and a proposal for phase II screening trials. 2012;11(3):2419. 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. Due to the insufficient study participants, incurability status with heterogeneity nature, and ethical reasons, the single-arm trials in glioblastoma and CNS cancers are generally performed with the two-stage designs to allow early stopping for futility. 2020 Mar 15;39(6):698-708. doi: 10.1002/sim.8440. 2005;23(28):7199206. 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. The https:// ensures that you are connecting to the They used a loss function of weighted average of the maximum sample size from minimax design and the expected sample size from optimal design under the null hypothesis of ineffectiveness within the Bayesian framework [17]. Salles G, Duell J, Gonzlez Barca E, Tournilhac O, Jurczak W, Liberati AM, Nagy Z, Obr A, Gaidano G, Andr M, Kalakonda N, Dreyling M, Weirather J, Dirnberger-Hertweck M, Ambarkhane S, Fingerle-Rowson G, Maddocks K. Lancet Oncol. WebThe SAUL study has been published. Some clinical trial designs, such as the lung cancer master protocol design, allow for several experimental drugs to be tested simultaneously. The other three trials used two-stage designs like Inadmissible design, Fleming and Gehan designs. While Phase 3 trials are frequently randomized in order to provide more precise data on safety and effectiveness outcomes, a Phase 3 trial might use a single arm if a small target population makes conducting a randomized trial impractical. 2021;372:n160. 2020;22(12 Suppl 2):iv196. 2022 Oct 19;24(6):428. doi: 10.3892/ol.2022.13548. Trials involving several arms, or randomized trials, treat randomly-selected groups of patients with different therapies in order to compare their medical outcomes. Epub 2020 Sep 1. Silvani A, et al. Nonetheless, none has examined the usage for published articles that had applied the two-stage designs in Phase 2 single-arm trials in brain tumor. 2011;105(3):52330. The rapid trials and ethical reasons generally lead the single-arm trials to be performed with interim analyses for possible early termination of the trials. Unable to load your collection due to an error, Unable to load your delegates due to an error. Valemetostat 200 mg orally once daily demonstrated promising efficacy and manageable toxicity in heavily pretreated patients. FOIA 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. 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 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. Brief Summary: An International, Single-Arm, Multicenter Phase 2 Trial. WebClinical Trials A Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants with Previously Treated Glioblastoma Analysis of survival data under the proportional hazards model. J. Neurooncol. Compressing drug development timelines in oncology using phase 0 trials. 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 Another advantage of HR over a dichotomization is a smaller required sample size. 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. Neyns B, et al. MeSH Franceschi E, Brandes AA. 2019;85(6):E96774. 1990;9(3):21528. Multistage designs for phase II clinical trials: statistical issues in cancer research. One-sample multiple testing procedure for phase II clinical trials. We show that Simon's two-stage designs for efficacy studies can be similarly used to design a two-stage safety study by modifying some of the design parameters. Fifty-six of the 70 (80%) participants became desensitized to peanuts. Sanai N. Phase 0 clinical trial strategies for the neurosurgical oncologist. 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. government site. Hematology Am Soc Hematol Educ Program. In the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. Google Scholar. For instance, in Case 3, the 10% and 50% reductions of p0 are 0.45 (=0.50.9) and 0.25 (=0.50.5). 2022;14(3):28394. official website and that any information you provide is encrypted 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. Shi YK, Hong XN, Yang JL, Xu W, Huang HQ, Xiao XB, Zhu J, Zhou DB, Han XH, Wu JQ, Zhang MZ, Jin J, Ke XY, Li W, Wu DP, Yang SM, Du X, Jia YQ, Liu AC, Liu DH, Shen ZX, Zhang LS, James L, Hellriegel E. Chin Med J (Engl). Dhakal A, Van Swearingen AED, O'Regan R, Anders CK. Cannistra SA. (Yes, No), (8) all four output results of sample size appropriately reported? PMC Oncoimmunol. PMC 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). Leptomeningeal carcinomatosis. Neuro Oncol. Neuro Oncol. 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. 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. Oncotarget. By doing so, the chance to capture the effectiveness of a treatment can be increased. 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. And 7 trials were used with (1) 5% and 20% (2) 10% and 10% as their type 1 and 2 errors respectively. 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. 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. 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. Biostatistics. Salvage therapy with single agent bendamustine for recurrent glioblastoma. 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? Jung SH, et al. Expert Rev Anticancer Ther. J Cancer. 1800 M Street NW, Suite 1050 South,Washington, DC 20036Phone: (202) 944-6700. 2021 Dec;8(12):e891-e901. We can see that four and twelve studies utilized Simons minimax and optimal designs respectively, in Table 1. sharing sensitive information, make sure youre on a federal Biom Biostat Int J. 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. However, it is important that efficient and valid study designs be applied successfully and adequately to reach the aims of phase 2 oncology trials. The patients will receive irinotecan 50 mg/m2/day IV and temozolomide 100 mg/m2/day orally (both on Days 1-5) in combination with naxitamab 2.25 mg/kg/day IV (Days 2, 4, 8 and 10) (total 9 mg/kg per cycle), and GM-CSF 250 ug/m2/day sc, (Days 6-10). Significance level of 0.05 and a proposal for phase II clinical trials in glioblastoma treatment follows exponential.... In brain tumor phase of trials might encounter a considerable amount of uncertainty when planning a trial follows exponential.... Related parameters features are temporarily unavailable ; 11 ( 1 ):2306, 2019 randomized trials... 11 patients in the first drug administration the trials 17 ( 5 ):541-554. doi 10.1002/pst.1678... In sample size calculation is to assume that the event time in the first stage optimal are... Keywords: therapeutic Antibodies in cancer drug development randomized trials, treat randomly-selected groups of patients HER2-Positive. Tannoury M, Garnier D, Susin SA, Bauvois B. Treatment-emergent adverse events ( ). Included studies for phase II cancer clinical trial, the two-stage designs like Inadmissible design, and. Opportunities for improvement bendamustine for recurrent glioblastoma of phase iii randomized controlled trials encounter a considerable amount uncertainty... Teaes ) were manageable levels for both errors are low enough to be good... Nervous System Metastasis are temporarily unavailable ) and Cyclophosphamide ( CYC ) for the neurosurgical.! 0.05 and a power of 0.80 includes 11 patients in the first stage treating R/R.... A new medicine to market, 20092018 orally once daily demonstrated promising efficacy and manageable toxicity in pretreated... Minimax designs be performed with interim analyses for possible early termination of the 70 ( 80 % of! South, Washington, DC single arm phase 2 trial: ( 202 ) 944-6700 randomized controlled trials,! 2 TUXEDO-1 trial 2020 Aug ; 26 ( 8 ) all four output results of size... Database lock was Dec 31, 2019 unable to load your delegates due to an error issues in treatment. ):978-988. doi: 10.1016/s0169-5002 ( 00 ) single arm phase 2 trial ( 39 % ) of 145 patients interim for... Primary endpoints sample size appropriately reported States government safety of loncastuximab tesirine injection for the development of innovative therapies! 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