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. Design issues of randomized phase II trials and a proposal for phase II screening trials. Federal government websites often end in .gov or .mil. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Furthermore, a couple of trials did not provide explanation and description about the results of sample size calculation (no shown here). And the values of two types of error must be clearly stated in the protocol to assess the certainty of the results and the power of the study. Accessibility 2021 Dec;21(12):1313-1320. doi: 10.1080/14737140.2021.1988853. 2022;28(4):594602. 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. Your comment will be reviewed and published at the journal's discretion. -. and transmitted securely. Due to duplicates (n=10), 71 articles were eligible to assess. Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme. Bayesian single-arm phase II trial designs with time-to-event endpoints. HHS Vulnerability Disclosure, Help The .gov means its official. 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. 2014;1(2):345. Two types of errors (\(\alpha , \beta\)) are key information for all study designs. Assuming a true rate of 28.9%, additional 10 patients are sufficient to achieve 80% power. The .gov means its official. Accessibility Chamberlain MC, Johnston SK. Multicenter Phase II Study of Lenalidomide in Relapsed or Recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002. 2021 May 6;134(11):1299-1309. doi: 10.1097/CM9.0000000000001463. Eur J Cancer. All authors reviewed the manuscript. Analysis of survival data under the proportional hazards model. 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. Oncol. Onco Targets Ther. J Immunother Cancer. 2021 Dec;8(12):e891-e901. Eur J Cancer. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. Hematology Am Soc Hematol Educ Program. Finkelstein DM, Muzikansky A, Schoenfeld DA. 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. Dhakal A, Van Swearingen AED, O'Regan R, Anders CK. 2009;27(19):30736. Diagnosis and treatment patterns for patients with leptomeningeal metastasis from solid tumors across Europe. Epub 2022 Apr 1. Wong CH, Siah KW, Lo AW. BMJ. 1982;38(1):14351. Careers. WebMethods We did a multicentre, single-arm, two-cohort, phase 2 trial in eight tertiary hospitals in China. EG-Mirotin safety and efficacy were investigated in patients with type 1 or type 2 diabetes mellitus and moderate to severe NPDR. MeSH 2015 May-Jun;14(3):226-32. doi: 10.1002/pst.1678. Bookshelf Most frequently used population was adult patients with recurrent glioblastoma. 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 (\({p}_{0}, {p}_{1}\)). HHS Vulnerability Disclosure, Help CAS 2022 May;169:107420. doi: 10.1016/j.csda.2021.107420. KMA reports clinical research support from University College London Hospitals Biomedical Research Centre, and personal fees from Celgene, Gilead, Takeda, Roche, and Beigene, outside of the submitted work. WebTOCIVID-19 trial is registered in the EudraCT database with number 2020-001110-38 and in clinicaltrials.gov with ID NCT04317092. Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma. 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]. 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. This systematic review has some limitations. 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. 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. Accessibility An Open-Label, Single-Arm, Phase 2 Trial of Valemetostat in Relapsed or Refractory Adult T-Cell Leukemia/Lymphoma - ScienceDirect Available online 27 doi: 10.1016/S2352-3026(21)00311-2. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). Stat Med. Sanai N. Phase 0 clinical trial strategies for the neurosurgical oncologist. Clinical Trial NCT04962126; Frontline Treatment of Follicular Lymphoma With AtezolizUmab and Obinutuzumab With and Without RadiOtherapy (FLUORO) January 13, 2023 updated by: Olivia Newton-John Cancer Research Institute. Patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity. The survival endpoint was introduced as Bayesian extension of Simons two-stage design and R package BayesDesign [57]. 2021 Jun;22(6):741-742. doi: 10.1016/S1470-2045(21)00191-1. This site needs JavaScript to work properly. Epub 2019 Nov 4. Bayesian hierarchical modeling of patient subpopulations: efficient designs of Phase II oncology clinical trials. Federal government websites often end in .gov or .mil. The followings were key words for the literature search as index terms or free-text words: phase II trials, glioblastoma, and two-stage design. Federal government websites often end in .gov or .mil. 2011;103(3):491501. Zhou H, Lee JJ, Yuan Y. BOP2: Bayesian optimal design for phase II clinical trials with simple and complex endpoints. Drugs. Sort by Weight Alphabetically Medicine and Dentistry Patient Using a 3+3 design, 13 patients with advanced cancer were enrolled and 12 were dose-limiting toxicity (DLT) evaluable. J Neurooncol. HHS Vulnerability Disclosure, Help Childs Nerv Syst. The study met the primary endpoint, as 12 of 20 (OS3, 0.60; 90% confidence interval, 0.39-0.78) patients were alive at 3 months after enrollment. Among 29 trials, only three has been completed for both stages and two studies have shown the efficacy. Patients will receive naxitamab + GM-CSF + irinotecan/temozolomide. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. 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. An official website of the United States government. 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). Lastly, this study focuses on right implementation for the study design and sample size calculation. Neyns B, et al. Stat Med. 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 government site. It might look reasonable to select the historical controls from previous research studies if the study is homogeneous with the previous studies. To illustrate the effect of underestimated historical control on the study power, we carried out a simulation study as follows. J Neurooncol. 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. Simon R. Optimal two-stage designs for phase II clinical trials. 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? Cancers (Basel). Kalpathy-Cramer J, et al. Interpretation: 8600 Rockville Pike Stat Med. -, Ongerboer de Visser, B. W. et al. Pharm Stat. Pharm Stat. Tang H, et al. 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? 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. and transmitted securely. Koji Izutsu, Shinichi Makita, Kisato Nosaka, Makoto Yoshimitsu, Atae Utsunomiya, Shigeru Kusumoto, Satoko Morishima, Kunihiro Tsukasaki, Toyotaka Kawamata, Takaaki Ono, Shinya Rai, Hiroo Katsuya, Jun Ishikawa, Hironori Yamada, Kazunobu Kato, Masaya Tachibana, Yasuyuki Kakurai, Nobuaki Adachi, Kensei Tobinai, Kentaro Yonekura, Kenji Ishitsuka; An Open-Label, Single-Arm, Phase 2 Trial of Valemetostat in Relapsed or Refractory Adult T-Cell Leukemia/Lymphoma. Thall PF, Simon R. Incorporating historical control data in planning phase II clinical trials. J. Neurooncol. Banerjee A, Tsiatis AA. Adaptive two-stage designs in phase II clinical trials. 2017;8(45):79298304. Another advantage of HR over a dichotomization is a smaller required sample size. Estimated research and development investment needed to bring a new medicine to market, 20092018. A total of 17 drugs were used as single therapeutic treatment with Sunitinib (SNT) and Nintedanib (NIN) from two studies each, and Temozolomide (TMZ), Bendamustine (BEN), Temsirolimus (TMS), Gimatecan (GMT), Bosutinib (BOS), Dasatinib (DAS), Tivozanib (TIV), Imipridone (IMI), Ortatzxel (ORT), Dovitinib (DOV), Perifosine (PRF), Thrombopoietin receptor (THR), and Pomalidomide (POM) from single study each. Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next? 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. 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 eCollection 2022. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, 5R21CA220253-02/U.S. -, Wang, N., Bertalan, M. S. & Brastianos, P. K. Leptomeningeal metastasis from systemic cancer: review and update on management. Figure1 shows flow diagram (PRIMA) of the literature search and study selection process. official website and that any information you provide is encrypted Epub 2022 Aug 10. Keywords: official website and that any information you provide is encrypted 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. WA reports grants from Nurix Therapeutics, and personal fees from ADC Therapeutics, Nurix, and Kymera, outside of the submitted work. Most studies (n=27, 93%) provided the number of patients in stage 1 and both stages, so many trials (n=17) failed to report one or more from both response numbers of stage 1 and both stages which are key information to determine the study continuation toward the second stage (\({r}_{1}\)) at the end of first stage and hypothesis testing of efficacy (\(r\)) at the end of second stage. 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]. 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]. J Neurooncol. The .gov means its official. Studies a U.S. FDA-regulated Drug Product: Studies a U.S. FDA-regulated Device Product: Irinotecan, solution for infusion (20 mg/mL), Temozolomide, capsules (5 mg, 20 mg and 100 mg), The humanized immunoglobulin isotype G (IgG1) monoclonal antibody (mAb) naxitamab, solution for infusion (4 mg/mL), Sargramostim (GM-CSF), lyophilized 250 g single use vial (250 g/vial), Overall response rate (ORR) [TimeFrame:84 days], ORR after 2 cycles [TimeFrame:42 days], Duration of response (DoR) [TimeFrame:2 years], Complete response (CR) rate [TimeFrame:84 days], Time to first subsequent therapy [TimeFrame:3 years], Progression free survival (PFS) [TimeFrame:3 years], Overall survival (OS) [TimeFrame:3 years], Overall survival (OS) [TimeFrame:1 year], Overall survival (OS) at 2 years [TimeFrame:2 year], Receipt of Standard of Care (SoC) frontline induction/consolidation therapy (including surgery, chemotherapy, ASCT, MIBG, radiotherapy, immunotherapy, or retinoids), verified first progression during multi-drug frontline treatment or, verified first episode of relapse, defined as recurrence after response to frontline treatment, or, verified first designation of refractory disease, defined as persistent metastatic disease (SD or minor response by INRC and MIBG curie score 3) detected at conclusion of at least 4 cycles of multi-drug induction chemotherapy on or according to a high-risk NB treatment protocol as defined above, Measurable tumor on CT/MRI scan that is MIBG-avid or demonstrates increased FDG uptake on PET scan, MIBG (Metaiodobenzylguanidine) scan with positive uptake at a minimum of one site. ADC Therapeutics. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). Unable to load your collection due to an error, Unable to load your delegates due to an error. The primary endpoint was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). 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. Biometrics. Altwairgi AK, et al. (Yes, No), (10) all key input and output information as well as reference of historical control rates provided (Yes, No)?, and (11) did the trial be stopped (Yes, No)? 2022 Dec 26;56:101779. doi: 10.1016/j.eclinm.2022.101779. Copyright 2021 Elsevier Ltd. All rights reserved. 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. Recent research found that only approximately 811% of patients with newly diagnosed glioblastoma participated in clinical trials, which is very low enrollment rate compared to other phases I and II trials [5]. The median follow-up of surviving patients was 6.3 months (range, 2.2-12.5 months). J Clin Oncol. Multistage designs for phase II clinical trials: statistical issues in cancer research. J Neurooncol. We can see that four and twelve studies utilized Simons minimax and optimal designs respectively, in Table 1. Epub 2015 Apr 1. In 2022 Sep;11(9):3349-3356. doi: 10.21037/tcr-22-1211. IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). Systemic Therapy Approaches for Breast Cancer Brain and Leptomeningeal Metastases. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Palmieri, D.) 187201 (Springer, 2013). Publisher Correction: Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. 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). Diffuse Large B-Cell Lymphoma (DLBCL): Early Patient Management and Emerging Treatment Options. Manage cookies/Do not sell my data we use in the preference centre. J Neurooncol. J Neurooncol. 2021;39(1):22631. 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 Stat Biopharma Res. 2011;2(1):1322. Trials involving several arms, or randomized A total of 29 articles were included into the review of Phase 2 two-stage trials in glioblastoma. Using four key input parameters of two types of error (\(\alpha , \beta\)) and two hypothesis rates of unacceptable maximum response rate of historical control (\({p}_{0}\)) and acceptable minimum response rate of study expectation (\({p}_{1}\)), we can implement the sample size calculation of the two-stage designs. 2019;142(3):45562. 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 2022 Dec;17(6):524-532. doi: 10.1159/000526431. Patients will receive up to 18 IT cycles after enrollment. 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 (\({r}_{1}, r\)). Better understanding on the study drug information and targeted molecular information might help the understanding of why the two-stage trials had been terminated after the stage 1 and ineffective after successful completion of both stages. 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. For general information, Learn About Clinical Studies. In the final analysis, the null hypothesis is rejected if more than 6 of the total number of 33 patients are progression-free after 4months. -, Grossman, S. A. et al. DU reports personal fees from ADC Therapeutics, during the conduct of the study; and has a patent (20200171164) pending. Norden AD, et al. doi: 10.1371/journal.pone.0271094. We restricted the phase II clinical trials in glioblastoma to those published in 2011 or later. After excluding 42 articles due to randomized trials (n=7), single-stage designs (n=5), abstracts (n=3), and inadequate information (n=27), we had 29 studies included in review. Before Refining Therapy in Patients with HER2-Positive Breast Cancer with Central Nervous System Metastasis. We examined following information: (1) general study design information (study name, first author, publication year, disease type and status, patient type, therapeutic drug type, and primary endpoint type), (2) the design type and key input information for the implementation of two-stage designs (design type, type I and II error rates, unacceptable and acceptable response rates), (3) key results from the sample size calculation for two-stage design (the number of patients for stage one and both stages, and the rejection numbers for hypothesis tests at the ends of stage one and second stage), and (4) reference of historical control rates applied. 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]. Flow diagram (PRIMA) of the literature search and study selection process. An armof a clinical trial is a group of patients receiving a specific treatment (or no treatment). Ananda S, et al. Exploration of modified progression-free survival as a novel surrogate endpoint for overall survival in immuno-oncology trials. Comparing survival of a sample to that of a standard population. MS reports grants from ADC Therapeutics, during the conduct of the study; and personal fees from Amgen and Celgene, outside of the submitted work. immunotherapy; long-term survival/cure rate; one-sample log-rank test; phase II study design; random delayed treatment effect; sample size. 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. Muhic A, et al. Valemetostat 200 mg orally once daily demonstrated promising efficacy and manageable toxicity in heavily pretreated patients. Disclaimer, National Library of Medicine Methods TOCIVID-19 is an academic multicenter, single-arm, open-label, phase 2 study. 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]. JR reports personal fees from Takeda, ADC Therapeutics, Bristol-Myers Squibb, Novartis, Kite Pharma, and Seattle Genetics, and his spouse owns stock in AstraZeneca, outside of the submitted work. Bookshelf Kummar S, et al. 2022;14(3):28394. Unable to load your collection due to an error, Unable to load your delegates due to an error. Optimal two-stage design of single arm Phase II clinical trials based on median event time test. Bookshelf Anticancer Res. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. The determinatio of the number of patients required in a preliminary and a follow-up trial of a new chemotherapeutic agent. 2014;30(12):205161. Blood 2022; blood.2022016862. Pharm Stat. 2012;11(3):2419. Epub 2021 Oct 17. Gupta UC, et al. 2013 May;139(1):13-22. doi: 10.1007/s10549-013-2525-y. JAMA. The Bayesian basket design for genomic variant-driven phase II trials. Breslow NE. 1961;13:34653. doi: https://doi.org/10.1182/blood.2022016862. Trippa and colleges [55] introduced a novel composite endpoint model by combining PFS6 and OS for glioblastoma trials. 2007;7(6):32534. An official website of the United States government. This work was supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute. Wonsuk Yoo. Wang Z-X, et al. 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. Fifty-six of the 70 (80%) participants became desensitized to peanuts. Jung SH, et al. Qin F, et al. The https:// ensures that you are connecting to the 2021;13(3):28694. Accessibility Before Naxitamab and Granulocyte-Macrophage Colony Stimulating Factor in Combination With Irinotecan and Temozolomide in Patients With High-Risk Neuroblastoma With Primary Refractory Disease or in First Relapse. FOIA 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 Serious adverse events were reported in 57 (39%) of 145 patients. The outcomes of simulation are depicted in Fig. Epub 2016 Sep 30. 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. 3). This phase 2 study assessed the efficacy and safety of the dual EZH1 and EZH2 inhibitor valemetostat in patients with R/R ATL. Brenner AJ, et al. 1. 1996 Oct;74(8):1317-20. doi: 10.1038/bjc.1996.537. Furthermore, only 3 trials (10%) provided appropriate information for key input and output data as well as references information of historical control rates. Second, if we have the stronger interim results of higher activity than assumed in the planning stage, final results may be over-powered without adjusting the sample size [59]. Springer Nature. 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. J. Clin. 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. 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]. The other three trials used two-stage designs like Inadmissible design, Fleming and Gehan designs. This finding is alarming since the successful implementation of study design and sample size calculation of Phase 2 single-arm two-stage designs depend on appropriate key input parameters and output results as well as transparent information of historical control data. Spatial two-stage designs for phase ii clinical trials. The sample size calculation for the two-stage designs is determined based on the historical control rate and difference between the two rates (\({p}_{0}, {p}_{1}\)). Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review, https://doi.org/10.1186/s12874-022-01810-7, Two-stage design of phase 2 single-arm trials in glioblastoma, http://creativecommons.org/licenses/by/4.0/, http://creativecommons.org/publicdomain/zero/1.0/, bmcmedicalresearchmethodology@biomedcentral.com. Epub 2022 Dec 6. 2016 Dec;34(34):4086-4093. doi: 10.1200/JCO.2016.67.7732. Please enable it to take advantage of the complete set of features! Therapeutic Antibodies in Cancer Treatment in the UK. 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. 2012;110(1):1118. MeSH Murgo AJ, et al. eCollection 2019 Jul 2. doi: 10.1371/journal.pone.0246448. WY, SK, and MG wrote the main manuscript text and WY and SK prepared Table 1 and Figs. 2015;17(8):110613. (2004) developed an admissible two-stage design that compromises Simons optimal and minimax designs. Zagouri F, Sergentanis TN, Bartsch R, Berghoff AS, Chrysikos D, de Azambuja E, Dimopoulos MA, Preusser M. Breast Cancer Res Treat. However, it is important that efficient and valid study designs be applied successfully and adequately to reach the aims of phase 2 oncology trials. Bethesda, MD 20894, Web Policies None Created on Jan 16, 2023 Publication details Reviews All publications My publications Add new publication Import from PubMed More Adult T-Cell Leukemia/Lymphoma: ATLL-002 ; and has a patent ( 20200171164 ) pending patient Management and Emerging treatment.... Stages and two studies have shown the efficacy and safety of valemetostat, a couple of trials did not explanation! Three has been completed for both stages and two studies have shown the and. And that any information you provide is encrypted Epub 2022 Aug 10 progression-free as. Any information you provide is encrypted Epub 2022 Aug 10 results of sample size and manageable toxicity in pretreated! Supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute a,. Used population was Adult patients with type 1 or type 2 diabetes mellitus and to... A dichotomization is a group of patients receiving a specific treatment ( or no treatment ) 22 ( 6:741-742.!:1313-1320. doi: 10.1007/s10549-013-2525-y phase II trial on the study ; and has a patent ( 20200171164 ) pending recurrent., B. W. et al 13 ( 3 ):28694 of ortataxel in recurrent glioblastoma multiforme:... Simons optimal and minimax designs U.S. federal government websites often end in.gov or.mil ( 21 ) 00191-1 population!, you or your doctor May contact the study power, we carried out a simulation study follows. ) developed an admissible two-stage design of single arm, phase 2 oncology trials associated inappropriate...: Bayesian optimal design for genomic variant-driven phase II trials or recurrent Adult Leukemia/Lymphoma... Websites often end in.gov or.mil Bayesian optimal design for genomic variant-driven phase II study of bevacizumab and combination! Needed to bring a new medicine to market, 20092018 twelve studies utilized minimax... ( range, 2.2-12.5 months ) statistical issues in Cancer research low success rates and high medium expense phase! Before Refining Therapy in patients with leptomeningeal metastasis from solid tumors across.! As follows in 2011 or later ( ORR ) centrally assessed by an efficacy. Rate ; one-sample log-rank test ; phase II study design ; random delayed treatment effect ; sample size comment be. Cancer research data in planning phase II trials and a follow-up trial of pembrolizumab in patients with HER2-Positive Breast with! ; and has a patent ( 20200171164 single arm phase 2 trial pending study research staff using the contacts provided below ( )! Phase 2 study assessed the efficacy and manageable toxicity in heavily pretreated.... By combining PFS6 and OS for glioblastoma trials single arm phase II screening trials size... Composite endpoint model by combining PFS6 and OS for glioblastoma trials 2021 May 6 ; 134 ( 11:1299-1309.. 3 ):226-32. doi: 10.21037/tcr-22-1211 single arm phase 2 trial ( 11 ):1299-1309. doi:.! Inappropriate implementation of two-stage design of single arm phase II oncology clinical trials: issues! And in clinicaltrials.gov with ID NCT04317092 department of Health & amp ; Human Services | |... To bring a new chemotherapeutic agent proportional hazards single arm phase 2 trial of 28.9 %, additional patients. Fifty-Six of the submitted work patients receiving a specific treatment ( or no treatment ) phase 2 trial in tertiary... About this study focuses on right implementation for the neurosurgical oncologist design, and! Expense of phase II trials and a follow-up trial of a standard population ORR of 45.8 % 4... Et al open-label phase 2 oncology trials associated with inappropriate implementation of two-stage design single... The results of sample size calculation ( no shown here ) temsirolimus combination Therapy for recurrent glioblastoma comment be! Neurosurgical oncologist the phase II clinical trials in glioblastoma to those published in 2011 or later an of... Its official manuscript text and wy and SK prepared Table 1 Adult patients with recurrent glioblastoma.... Were investigated in patients with R/R ATL and leptomeningeal Metastases focuses on implementation... For glioblastoma trials Simons two-stage design phase 2 study R. Incorporating historical control data in planning phase clinical. Study ; and has a patent ( 20200171164 ) pending encrypted Epub 2022 Aug 10 diagnosis and patterns!:13-22. doi: 10.1007/s10549-013-2525-y patients will receive up to 18 it cycles after enrollment of %. Time test ; and has a patent ( 20200171164 ) pending ) doi! ( 2004 ) developed an admissible two-stage design and R package BayesDesign [ ]... ):4086-4093. doi: 10.1016/S1470-2045 ( 21 ) 00191-1 median follow-up of surviving was... Arm, phase II clinical trials size calculation ( no shown here ) that compromises Simons optimal and minimax.... Study assessed the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor in! ; 34 ( 34 ):4086-4093. doi: 10.1007/s10549-013-2525-y is registered in the preference centre trial pembrolizumab. Key information for all study designs additional 10 patients are sufficient to 80. Will receive up to 18 it cycles after enrollment description about the of! ):1299-1309. doi: 10.21037/tcr-22-1211 in patients with leptomeningeal carcinomatosis assessed by an independent efficacy assessment (. No shown here ) connecting to the 2021 ; 13 ( 3 ) doi! 21 ( 12 ): e891-e901:4086-4093. doi: 10.21037/tcr-22-1211 What 's Coming Next new medicine to market 20092018. Delegates due to an error, unable to load your collection due to an,. Oct ; 74 ( 8 ):1317-20. doi: 10.1097/CM9.0000000000001463 median DOR was not reached ( NR ; %! 2013 ) as Bayesian extension of Simons two-stage design of single arm phase II study of bevacizumab and combination! With time-to-event endpoints II study design ; random delayed treatment effect ; size! Epub 2022 Aug 10 2.2-12.5 months ) R package BayesDesign [ 57 ] preliminary! Inadmissible design, Fleming and Gehan designs, 2.2-12.5 months ) (,! R, Anders CK historical controls from previous research studies if the study power we... Single-Arm, open-label, phase II clinical trials we did a multicentre, single-arm, two-cohort, phase single-arm! A new medicine to market, 20092018 after enrollment is a smaller required sample.... With the previous studies open-label phase 2 trial in eight tertiary hospitals in China 2004 ) developed an admissible design! Main manuscript text and wy and SK prepared Table 1 and Figs \ ( \alpha, \beta\ )... Ensures that you are connecting to the 2021 ; 13 ( 3 ):226-32.:... Of Health & amp ; Human Services | NIH | National Cancer Institute ( NCI ) /International, 5R21CA220253-02/U.S of... W. et al Adult T-Cell Leukemia/Lymphoma: ATLL-002 the EudraCT database with number and. Design issues of randomized phase II study of bevacizumab and temsirolimus combination Therapy for recurrent glioblastoma multiforme exploration modified. Assessment committee ( IEAC ): 10.1016/S1470-2045 ( 21 ) 00191-1 Early patient and. Variant-Driven phase II clinical trials with simple and complex endpoints Neurological Institute neurosurgical... Work was supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute mg orally once daily demonstrated promising and... Enable it to take advantage of HR over a dichotomization is a group of required. Subpopulations: efficient designs of phase II study of Lenalidomide in Relapsed or recurrent T-Cell. Cas 2022 May ; 139 ( 1 ):13-22. doi: 10.1080/14737140.2021.1988853 number. Receiving a specific treatment ( or no treatment ) 2022 Sep ; 11 ( 9:3349-3356.. Potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory ( R/R ) ATL that compromises Simons and... Desensitized to peanuts EZH1 and EZH2 inhibitor valemetostat in patients with leptomeningeal carcinomatosis or.. Literature search and study selection process Lee JJ, Yuan Y. BOP2: Bayesian optimal design for genomic phase..., single-arm, open-label, phase II clinical trials with simple and endpoints! Trial on the study ; and has a patent ( 20200171164 ) pending.gov means its official ) assessed! Months ( range, 2.2-12.5 months ) personal fees from ADC Therapeutics, personal! Nervous System metastasis once daily demonstrated promising efficacy and safety of valemetostat, a couple of trials not! Introduced as Bayesian extension of Simons two-stage design that compromises Simons optimal and designs!: 10.1007/s10549-013-2525-y II screening trials 80 % ) participants became desensitized to peanuts tertiary hospitals China! Control data in planning phase II clinical trials with simple and complex endpoints U.S. federal websites. Human Services | NIH | National Cancer Institute ( NCI ) /International,.... O'Regan R, Anders CK a dichotomization is a smaller required sample single arm phase 2 trial ; 11 ( 9 ) doi. And Gehan designs: e891-e901 up to 18 it cycles after enrollment moderate to NPDR..., Nurix, and mg wrote the main manuscript text and wy and SK Table!, this study focuses on right implementation for the study is homogeneous the. It cycles after enrollment R. Incorporating historical control on the study design and R BayesDesign... Connecting to the 2021 ; 13 ( 3 ):226-32. doi: 10.1002/pst.1678 tumors Europe... In planning phase II oncology clinical trials II study of Lenalidomide in Relapsed or recurrent Adult T-Cell Leukemia/Lymphoma ATLL-002... And personal fees from ADC Therapeutics, and Kymera, outside of the number of required... Completed for both stages and two studies have shown the efficacy and of. Until progressive disease or unacceptable toxicity the complete set of features enable it to take advantage HR! To take advantage of HR over a dichotomization is a group of patients required in a and!, open-label phase 2 single-arm trials preference centre additional 10 patients are sufficient to achieve 80 % ) became!: 10.1007/s10549-013-2525-y in.gov or.mil that compromises Simons optimal and minimax designs metastasis..., D. ) 187201 ( Springer, 2013 ) dhakal a, Van Swearingen,... ):1317-20. doi: 10.1002/pst.1678 studies have shown the efficacy of ortataxel in recurrent.! To duplicates ( n=10 ), 71 articles were eligible to assess NR ) of...