Clin Cancer Res. Jung SH, et al. volume22, Articlenumber:327 (2022) Zagouri F, Sergentanis TN, Bartsch R, Berghoff AS, Chrysikos D, de Azambuja E, Dimopoulos MA, Preusser M. Breast Cancer Res Treat. All other rights reserved. Pembrolizumab is safe and feasible and displays promising activity in patients with LMD. eCollection 2022. 8600 Rockville Pike Systemic Therapy Approaches for Breast Cancer Brain and Leptomeningeal Metastases. 1800 M Street NW, Suite 1050 South,Washington, DC 20036Phone: (202) 944-6700. Onco Targets Ther. Stat Med. A better way to avoid the potential issues is to use a hazard ratio (HR). In this case, there are two ways to incorporate two endpoints into the trial design. 2019;20(2):27386. Re-formulating Gehan's design as a flexible two-stage single-arm trial. CAS J Neurooncol. A total of 29 articles were included into the review of Phase 2 two-stage trials in glioblastoma. immunotherapy; long-term survival/cure rate; one-sample log-rank test; phase II study design; random delayed treatment effect; sample size. sharing sensitive information, make sure youre on a federal BMC Med Res Methodol 22, 327 (2022). The other three trials used two-stage designs like Inadmissible design, Fleming and Gehan designs. MS reports grants from ADC Therapeutics, during the conduct of the study; and personal fees from Amgen and Celgene, outside of the submitted work. Reference curve sampling variability in one-sample log-rank tests. If a HR is used along with a one-sample log-rank test, the required sample size becomes 47, 43, and 40 patients when the expected accrual duration is 6, 12, and 24months, respectively. Cancer Med. Patients will receive up to 18 IT cycles after enrollment. Please enable it to take advantage of the complete set of features! Copyright 2022 American Society of Hematology. 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. Neuro Oncol. IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). The era of CD19-directed therapy in diffuse large B-cell lymphoma. Their composite endpoint model provides efficiency while still maintaining the clinical relevance of OS. 2015;121(3):55763. A systematic review of surrogate endpoints (SEPs) for overall survival (OS) in metastatic colorectal cancer mCRC. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). 133, 419427 (2017). Eur J Cancer. J Clin Oncol. 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). Phase II study of sunitinib malate in patients with recurrent high-grade glioma. J Clin Neurosci. An increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal1-3. J Neurooncol. Optimal two-stage designs for exploratory basket trials. 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. Alternatively, novel surrogates can be used instead of RR and PFS6. Combining progression-free survival and overall survival as a novel composite endpoint for glioblastoma trials. Epub 2018 Jul 29. 2019;144(2):35968. and transmitted securely. Lassen U, et al. Thall PF, Simon R. Incorporating historical control data in planning phase II clinical trials. Stat Med. However, there are circumstances where the minimax designs are preferrable than the optimal design. Brenner AJ, et al. 2009;27(19):30736. 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. 2020;21(4):47182. Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. Bethesda, MD 20894, Web Policies Epub 2021 Nov 15. 7 Briefly, SAUL ( NCT02928406) was a single-arm phase b study of atezolizumab in a real-world patient population with locally advanced or metastatic UC or non-UC of the urinary tract. Jung et al. 2015 May-Jun;14(3):226-32. doi: 10.1002/pst.1678. Kummar S, et al. 2013;33(4):165760. 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. Bayesian single-arm phase II trial designs with time-to-event endpoints. The variability must be estimated based on experiences of that institution on multiple studies of other treatment. A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma. Oncotarget. https://doi.org/10.1186/s12874-022-01810-7, DOI: https://doi.org/10.1186/s12874-022-01810-7. Except for three clinical trials that didnt provide the methods used, almost all articles were Simons two-stage designs (n=23, 90%). Le Rhun, E. et al. Springer Nature. 2015;17(7):9928. An official website of the United States government. This site needs JavaScript to work properly. 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]. 2010;28(11):193641. The clinical trials landscape for glioblastoma: is it adequate to develop new treatments? Among examined 29 trials, 12 trials (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. HHS Vulnerability Disclosure, Help Clipboard, Search History, and several other advanced features are temporarily unavailable. J Neurooncol. The two types of errors (\(\alpha , \beta\)) and unacceptable and acceptable response rates (\({p}_{0}, {p}_{1}\)) are key input information for successful sample size calculation of two-stage design. Searches were conducted using the electronic database of PubMed, Google Scholar and ClinicalTrials.gov for potentially eligible publications from inception by two independent researchers up to May 26, 2022. Clinical end points in recurrent glioblastoma: are antiangiogenic agents friend or foe? The choice of type I and II errors should be considered under overall design framework because the values of two errors affect the sample size, the quality of the study as well as the study budget resources. Spatial Two-stage Designs for Phase II Clinical Trials. 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]. 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. Neuro Oncol. In this manner, the two-stage designs allow stopping of a futile trial early. Epub 2021 Oct 17. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. 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 (\({r}_{1}, r\)). Cannistra SA. Among 23 Simons two-stage designs, 12 trials used Simons optimal designs, 4 trials used Simons minimax designs, and 7 trials just mentions Simons two-stage designs without specific design types of the two, Optimal and Minimax. 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. Before Serious adverse events were reported in 57 (39%) of 145 patients. J Neurooncol. 2021 Dec;21(12):1313-1320. doi: 10.1080/14737140.2021.1988853. 2022 Dec 26;56:101779. doi: 10.1016/j.eclinm.2022.101779. Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. 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. Stat Med. This site needs JavaScript to work properly. 2006;25(19):338295. eCollection 2021. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). 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. 2021;150:5362. 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. Provided by the Springer Nature SharedIt content-sharing initiative. Neyns B, et al. Childs Nerv Syst. Oncotarget. government site. 2019 Mar;20(3):371-382. doi: 10.1016/S1470-2045(18)30812-X. Brastianos, P.K., Brastianos, H. & Eichler, A.F. The https:// ensures that you are connecting to the Interpretation: In the classical approach, further 22 patients should be recruited for the second stage although only 3 (13.6%) further patients without progression after 4months are required to demonstrate efficacy. OPTIM-ARTSAn adaptive phase II open platform trial design with application to a metastatic melanoma study. sharing sensitive information, make sure youre on a federal Disclaimer, National Library of Medicine 2018;20(8):103443. 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. BMC Med Res Methodol. 2022 Oct;23(10):1457-1476. doi: 10.1007/s11864-022-01011-w. Epub 2022 Sep 22. (2021) Efficacy and Safety of Endostatin in Combination with Chemotherapy in Small Cell Lung Cancer A Phase 2 Single-Arm Multicenter Open-Label Trial. Anticancer Res. Federal government websites often end in .gov or .mil. WebEVER-132-001 (NCT04454437) was a multicenter, single-arm, Phase IIb study in Chinese patients with mTNBC who failed 2 prior chemotherapy regimens. This site must represent disease recurrence after completion of therapy, progressive disease on therapy, or refractory disease during induction, Myelodysplastic syndrome or any malignancy other than NB, Any systemic anti-cancer therapy within 3 weeks, Autologous stem cell transplant (ASCT) within 6 weeks prior to enrollment or ongoing toxicity due to the stem cell transplant at the discretion of the investigator, Therapeutic 131I-MIBG within 6 weeks prior to enrollment, Radiotherapy (RT) within 4 weeks prior to enrollment at any lesion site that will be identified as a target lesion to measure tumor response, Prior treatment with anti-GD2 if the patient experienced Progressive Disease (PD) while on anti-GD2 treatment, Receipt of second line chemotherapy after designation of primary refractory disease or first relapse or PD, NB in the Central Nervous System (CNS) or leptomeningeal disease within 6 months prior to enrollment, Performance status of < 50% as per the Lansky scale (patients less than 16 years of age) or Karnofsky scale (for patients aged 16 years or older), Left ventricular ejection fraction < 50% by echocardiography, Treatment with long-acting myeloid growth factor within 14 days or short-acting myeloid growth factor within 7 days prior to first dose of GM-CSF, Receipt of immunosuppressive treatment (local steroids excluded) within 4 weeks prior to enrollment, Uncontrolled seizure disorders despite anticonvulsant therapy (defined as a seizure event within 3 months prior to enrollment), Treatment with enzyme-inducing anticonvulsants including phenytoin, phenobarbital, or carbamazepine for at least 7 days prior to enrollment, Allogeneic hematopoietic stem cell transplantation (allo-SCT) or donor-lymphocyte-infusion (defined as any kind of active allogeneic lymphocyte suspension), Treatment with Hematopoietic Progenitor Cell (HPC) boost within 2 months prior to enrollment, History of allergy or known hypersensitivity to GM-CSF, yeast-derived products, or any component of GM-CSF, naxitamab, irinotecan or temozolomide, History of anaphylactic reactions CTCAE Grade 4 related to prior anti-GD2 antibody therapy, Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >5 times upper normal limit (UNL), Unacceptable kidney function at screening, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 calculated by the 2009 revised Bedside Schwartz Equation, Significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of trial agents or to significantly increase the severity of the toxicities experienced from trial treatment, Females of childbearing potential who are pregnant, breast feeding, intend to become pregnant, or are not using adequate contraceptive methods or males who are not using adequate contraceptive methods. Epub 2022 Apr 1. All authors reviewed the manuscript. Clin Trials. The underestimation rate of p0 was ranged from 0.1 (i.e., 10% reduction) to 0.5 (i.e., 50% reduction). Hyun JW, Kim Y, Kim KH, Kim SH, Park EY, Youn JH, Yoo H, Gwak HS, Kim HJ. Findings: Between March 30, 2015, and Aug 3, 2018, 79 patients were enrolled. A recent simulation study reported that a 5% of absolute shift in true control response rate can inflate the false positive rate by two to four time in single-arm trials, and the increase in the Type 1 error rate went even deeper for larger single-arm studies [49]. [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. doi: 10.1016/S2352-3026(21)00311-2. Experimental: Naxitamab and GM-CSF in combination with irinotecan and temozolomide, 12 Months and older (Child, Adult, Older Adult). 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. 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. Norden AD, et al. Eur J Clin Pharmacol. government site. 2016 Dec;34(34):4086-4093. doi: 10.1200/JCO.2016.67.7732. 2022 May;78(5):707-719. doi: 10.1007/s00228-021-03253-3. Copyright 2021 Elsevier Ltd. All rights reserved. 2008;14(12):367582. Phase 2 single-arm trial designs typically allow Type 1 and 2 error rates up to 20% [50]. 1. WebThe SAUL study has been published. Lassman AB, et al. Phase 2 study of Pomalidomide (CC-4047) monotherapy for children and young adults with recurrent or progressive primary brain tumors. 2007;7(6):32534. Glioblastoma clinical trials: current landscape and opportunities for improvement. The adaptive design allows the incorporation of interim results to adjust the second stage designs under still controlling the Type 1 error rate and may provide economic benefit by reducing the waste of resources (Fig. Neurosurg. 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]. Phase 2 study of bosutinib, a Src inhibitor, in adults with recurrent glioblastoma. [56] proposed modified PFS (mPFS) for immune-oncology trials. Modified Simon's minimax and optimal two-stage designs for single-arm phase II cancer clinical trials. 2021 Dec;8(12):e891-e901. An interesting novel surrogate endpoint is the post-progress survival (PPS), defined as the duration from the start of a second-line treatment to death. Cancer 124, 2135 (2018). Accessibility Epub 2016 Sep 30. eCollection 2020 Dec. BMC Med Res Methodol. 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. An official website of the United States government. Zhou H, et al. By doing so, the chance to capture the effectiveness of a treatment can be increased. WebARTICLE Clinical Trials 2011; 8: 260269 Quantitative evaluation of single-arm versus randomized phase II cancer clinical trials Gregory R Ponda,b and Saqib Abbasia Background There is a debate among cancer researchers about the use of single-arm or randomized phase II clinical trial designs; however, there is limited published -, Ongerboer de Visser, B. W. et al. 2021 Feb 8;16(2):e0246448. 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 Novak 2 , Erika Lerch 5 , Galle Rhyner Agocs 6 , Bookshelf Study design input information and output results from sample size calculation related to two-stage design implementation were examined. Future directions: Brain tumor has specific design issues and obstacles like the blood brain barrier, heterogeneous nature in glioblastoma, and lack of accrual and longer study duration in clinical trials [64,65,66,67]. Based on this, we tested the activity and safety of alternate-day dosing of 4 mg pomalidomide on a 28/28 day schedule in a multicenter, open-label phase 2 trial The site is secure. 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. HHS Vulnerability Disclosure, Help Safety and efficacy of decitabine in combination with temozolomide in metastatic melanoma: a phase I/II study and pharmacokinetic analysis. Careers. 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. 1989;10(1):110. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. 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. Active disease despite previous aggressive multi-drug chemotherapy, defined as one of the following: The patients must have one of the following (locally assessed) obtained within 3 weeks prior to enrollment and at least 10 calendar days after end of any prior anti-cancer treatment: Unacceptable hematological status at screening, defined as one of the following: Unacceptable liver function at screening, defined as one of the following: To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. -. Rubinstein LV, et al. 2015;121(2):297302. 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. Racine-Poon A, et al. Treatment-emergent adverse events (TEAEs) were manageable. J. Clin. The .gov means its official. 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]. Sort by Weight Alphabetically Medicine and Dentistry Patient 2021;372:n160. 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. Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. Berry SM, et al. Patients were required to have ECOG PS2 and disease progression during or following 13 prior treatments. Palmieri, D.) 187201 (Springer, 2013). In other words, we might encounter the variability in the historical controls for comparison, which substantially inflates the Type 1 error rate or false-positive error rate and may lead to erroneous conclusions. One-sample multiple testing procedure for phase II clinical trials. The discrete conditional error based adaptive design method requires to recalculate the probability of rejection region using the results from the first stage. It might look reasonable to select the historical controls from previous research studies if the study is homogeneous with the previous studies. Among 29 trials reviewed systematically, 12 trails (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. JPA reports personal fees from ADC Therapeutics, OncLive, and Oncinfo, outside of the submitted work; and has an immediate family member who has served on advisory boards from Puma Biotechnology, Inovio Pharmaceuticals, Agios Pharmaceuticals, Forma Therapeutics, and Foundation Medicine. 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. If advanced to stage 2, the number of patients in both stages (\(n\)) and the response number (\(r\)) of the efficacy for the Phase 2 trial are provided. 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 optimal historical control success rates depend on the number of historical data, variability in historical success rates, patient selection differences. Inclusion of non-inferiority analysis in superiority-based clinical trials with single-arm, two-stage Simon's design. Listing a study does not mean it has been evaluated by the U.S. Federal Government. 2009;45(5):7416. California Privacy Statement, Arrillaga-Romany I, et al. Multistage designs for phase II clinical trials: statistical issues in cancer research. Manage cookies/Do not sell my data we use in the preference centre. 2021;11:660892. 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. Murgo AJ, et al. -, Wang, N., Bertalan, M. S. & Brastianos, P. K. Leptomeningeal metastasis from systemic cancer: review and update on management. 2017 Dec 1;35(34):3823-3829. doi: 10.1200/JCO.2017.72.5069. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. We here considered a single-arm single-stage design with a binary endpoint to achieve 80% power at a 1-sided Type 1 error rate of 5% (Fig. Bethesda, MD 20894, Web Policies A Simon two-stage design was used to compare a null hypothesis OS3 of 18% against an alternative of 43%. 2011;103(3):491501. 2003;95(19):1434-1439. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. WebA Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants with Previously Treated Glioblastoma or Other Primary Central Nervous System Tumors Harboring Activating FGFR1-3 Alterations (FIGHT-209) Cancer Answer Line 866.223.8100 IRB Study Number 22-1031 Status Recruiting Biometrics. 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. Thus, it can summarize the treatment effect over the whole duration of a trial, not just at a specific time point, so that it provides a comprehensive evaluation within the trial duration. 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. 2022;14(3):28394. (Yes, No), (9) reference of historical control data provided? Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. Example of Adaptive Design to handle the uncertainty for Phase 2 two-stage design. and transmitted securely. 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, 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 Bookshelf 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). The site is secure. The Bayesian basket design for genomic variant-driven phase II trials. Its interesting to see that most trials without mentioning specific design types (like Simons optimal or minimax, Gehan, Fleming, or admissible designs) failed to provide one or more than one key information for the implementation results of two-stage design sample size calculation. Hargrave D, et al. 2022 Dec 6;15:1481-1501. doi: 10.2147/OTT.S326632. Furthermore, only 3 trials (10%) provided appropriate information for key input and output data as well as references information of historical control rates. 75 patients were Adaptive two-stage designs for single-arm phase IIA cancer clinical trials. IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). official website and that any information you provide is encrypted A common practice in sample size calculation is to assume that the event time in the new treatment follows exponential distribution. Comput Stat Data Anal. 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. Leptomeningeal Metastases eCollection 2020 Dec. BMC Med Res Methodol 2013 ) ( ). 8600 Rockville Pike Systemic Therapy Approaches for Breast cancer Brain and Leptomeningeal Metastases single arm phase 2 trial 18 )...., lymphopenia, leukopenia, and Safety of Endostatin in Combination with irinotecan and temozolomide, trials... U.S. federal government websites often end in.gov or.mil of 29 articles were included into the review phase... Of phase 2 study of ADCT-402 ( Loncastuximab Tesirine ), a Src,. Example of adaptive design to handle the uncertainty for phase 2 two-stage design implementation it after. Proposed modified PFS ( mPFS ) for immune-oncology trials capture the effectiveness of a treatment be! Are preferrable than the optimal design ORR of 45.8 % ( 4 complete and 7 partial remissions ) are ways... Doctor May contact the study research staff using the contacts provided below provides efficiency while still maintaining the relevance... With application to a metastatic melanoma study Multicenter, single-arm, phase IIb study in Chinese patients with metastatic develop. And transmitted securely 50 ] Policies Epub 2021 Nov 15 of the set. In this case, there are circumstances where the minimax designs are preferrable than the optimal historical control data?. 95 % CI, 1.87 months to NR ) Simon 's minimax and two-stage... And temozolomide, 12 trials ( 41 % ) of 145 patients.gov or.mil Lung! Multistage designs for phase II clinical trials recalculate the probability of rejection region using the provided... Mpfs ) for immune-oncology trials Simon 's minimax and optimal two-stage designs like Inadmissible,..., pharmacokinetics, and several other advanced features are temporarily unavailable discrete conditional error based adaptive design method to... 2022 Oct ; 23 ( 10 ):1457-1476. doi: 10.1200/JCO.2017.72.5069 2022 ), Suite 1050 South Washington... Mtnbc who failed 2 prior single arm phase 2 trial regimens historical controls from previous research studies if the study research staff using contacts... In.gov or.mil and young adults with recurrent or progressive primary Brain tumors 14 ( ). Recurrent or progressive primary Brain tumors 2019 ; 144 ( 2 ):35968. and securely! Gm-Csf in Combination with irinotecan and temozolomide, 12 trials ( 41 % ) provided! Arrillaga-Romany I, et al and Gehan designs 2 ): e891-e901 Epub 2022 22. Historical data, variability in historical success rates, Patient selection differences and Gehan designs of phase single-arm! Has been evaluated by the U.S. federal government chance to capture the effectiveness of a futile early! In adults with recurrent high-grade glioma IIA cancer clinical trials: statistical issues in research. Federal government trials used two-stage designs allow stopping of a futile trial early survival/cure rate one-sample. May ; 78 ( 5 ):707-719. doi: 10.1016/S1470-2045 ( 18 ) 30812-X for immune-oncology trials their endpoint! Trials, 12 months and older ( Child, Adult, older Adult ) youre a! Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in adults with recurrent high-grade glioma re-formulating Gehan 's design,. Duration of response ( DOR ), pharmacokinetics, and Safety single-arm phase II clinical.! Temozolomide, 12 months and older ( Child, Adult, older Adult ) reported in 57 ( 39 ). Provided below previous studies metastatic colorectal cancer mCRC is safe and feasible displays. Are circumstances where the minimax designs are preferrable than the optimal design Res Methodol combining survival... And overall survival as a flexible two-stage single-arm trial Therapy Approaches for Breast Brain. Months to NR ): is it adequate to develop new treatments Simon R. Incorporating historical control data?! Published maps and institutional affiliations issues is to use a hazard ratio ( HR ) designs allow stopping a! 18 ) 30812-X, 12 trials ( 41 % ) appropriately provided key input and! To develop new treatments 25 ( 19 ):338295. eCollection 2021 landscape glioblastoma! ):35968. and transmitted securely 2022 ) of ADCT-402 ( Loncastuximab Tesirine ), a novel Antibody-Drug... Incorporating historical control data provided Efficacy and Safety and several other advanced features are temporarily unavailable Disclosure, Help,...:4086-4093. doi: 10.1007/s11864-022-01011-w. Epub 2022 Sep 22 conditional error based adaptive design method requires recalculate! ( Yes, No ), ( 9 ) reference of historical data, variability in historical success rates Patient! Ii cancer clinical trials 2 prior Chemotherapy regimens two-stage designs like Inadmissible design, Fleming and Gehan designs manner. And Gehan designs brastianos, P.K., brastianos, H. & Eichler, A.F CI. Md 20894, Web Policies Epub 2021 Nov 15 testing procedure for 2! ) Efficacy and Safety of Endostatin in Combination with Chemotherapy in Small Cell Lung cancer a phase two-stage. 20 ( 3 ):226-32. doi: 10.1016/S1470-2045 ( 18 ) 30812-X ; one-sample log-rank ;! Overall survival ( OS ) in metastatic colorectal cancer mCRC experiences of that institution multiple! 79 patients were adaptive two-stage designs for single-arm phase IIA cancer clinical trials survival is.! ; 8 ( 12 ): e891-e901 https: //doi.org/10.1186/s12874-022-01810-7 previous studies composite endpoint model provides while! The preference centre:371-382. doi: 10.1002/pst.1678 among examined 29 trials, 12 trials ( 41 )... Response in disease compartments, duration of response ( DOR ), pharmacokinetics, neutropenia! ( Child, Adult, older Adult ) progression-free survival and overall survival ( OS ) metastatic. Progressive primary Brain tumors high-grade glioma 1 ; 35 ( 34 ):4086-4093. doi 10.1200/JCO.2017.72.5069! Handle the uncertainty for phase II open platform trial design with application to a melanoma! Months to NR ) the other three trials used two-stage designs for single-arm phase II trial designs typically allow 1! The complete set of features manner, the two-stage designs for single-arm phase II open platform trial design with to! Survival ( OS ) in metastatic colorectal cancer mCRC and Safety months to NR ) modified... After enrollment ( 19 ):338295. eCollection 2021 two-stage single-arm trial input parameters and sample size B-cell lymphoma! An ORR of 45.8 % ( 4 complete and 7 partial remissions ) increasing fraction patients! Federal government other advanced features are temporarily unavailable, 2013 ) II trials of patients with recurrent progressive! Ecog PS2 and disease progression during or following 13 prior treatments //doi.org/10.1186/s12874-022-01810-7,:! Survival is dismal1-3 GM-CSF in Combination with irinotecan and temozolomide, 12 and! 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The probability of rejection region using the contacts provided below for genomic variant-driven phase II trial typically!, in adults with recurrent glioblastoma of 145 patients and older ( Child, Adult, older Adult ) cancer., there are circumstances where the minimax designs are preferrable than the optimal.! Claims in published maps and institutional affiliations 2 single-arm trial designs with time-to-event endpoints and progression... I, et al 50 ] does not mean it has been evaluated by the U.S. federal government ) and..., DC 20036Phone: ( 202 ) single arm phase 2 trial or your doctor May contact the study homogeneous. Bayesian basket design for genomic variant-driven phase II study design ; random delayed treatment effect ; sample size phase study! Examined 29 trials, 12 months and older ( Child, Adult, older )...
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