Lassen U, et al. Phase II and biomarker study of programmed cell death protein 1 inhibitor nivolumab and metronomic cyclophosphamide in paediatric relapsed/refractory solid tumours: Arm G of AcSe-ESMART, a trial of the European innovative therapies for children with cancer consortium. Disclaimer, National Library of Medicine https://doi.org/10.1186/s12874-022-01810-7, DOI: https://doi.org/10.1186/s12874-022-01810-7. Kim and Wong (2022) recently introduced novel designs that compromise on the two optimality criteria using the spatial information on the first stage's required sample size and the total required sample size [52]. Listing a study does not mean it has been evaluated by the U.S. Federal Government. If the parameters of two-stage designs (\({p}_{0}, {p}_{1}\)) are given, there are infinitely many two-stage designs satisfying the (\({\alpha }^{*}, {\beta }^{*})\) condition. Patients will receive naxitamab + GM-CSF + irinotecan/temozolomide. Murgo AJ, et al. Such a study design may not be suitable for immunotherapy cancer trials, when both long-term survivors (or even cured patients from the disease) and delayed treatment effect are present, because exponential distribution is not appropriate to describe such data and consequently could lead to severely underpowered trial. volume22, Articlenumber:327 (2022) Mateos et al. Trials involving several arms, or randomized trials, treat randomly-selected groups of patients with different therapies in order to compare their medical outcomes. 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 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. EG-Mirotin safety and efficacy were investigated in patients with type 1 or type 2 diabetes mellitus and moderate to severe NPDR. Mol Interv. Kim S, Wong WK. 2021 Dec;8(12):e891-e901. Together they form a unique fingerprint. 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. Cancers (Basel). Glioblastoma clinical trials: current landscape and opportunities for improvement. Table 1 is the summary of the included studies [18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46]. Altwairgi AK, et al. In addition, the several trials provided wrong results from sample size calculation even if they reported all related key information for two-stage design implementation (not shown in table). J Clin Oncol. ADC Therapeutics. Neuro Oncol. Would you like email updates of new search results? 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. MS reports grants from ADC Therapeutics, during the conduct of the study; and personal fees from Amgen and Celgene, outside of the submitted work. 2001 May;32(2):155-62. doi: 10.1016/s0169-5002(00)00220-8. Epub 2022 Aug 10. 2019;10(14):321423. National Cancer Center Hospital, Tokyo, Japan. government site. Estimation of clinical trial success rates and related parameters. [56] proposed modified PFS (mPFS) for immune-oncology trials. Keywords: In Multicenter Phase II Study of Lenalidomide in Relapsed or Recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002. WebIn the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. Burzynski SR, et al. Cancer immunotherapy trial design with cure rate and delayed treatment effect. 2019 Jul 2;10(42):4255-4261. doi: 10.18632/oncotarget.26981. Jung SH, et al. 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. Diagnosis and treatment patterns for patients with leptomeningeal metastasis from solid tumors across Europe. 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 Estimated research and development investment needed to bring a new medicine to market, 20092018. Du XJ, et al. This multicenter phase 2 trial (NCT04102150; https://clinicaltrials.gov/ct2/show/NCT04102150; DS3201-A-J201) enrolled patients with R/R aggressive ATL (acute, lymphoma, unfavorable chronic type). This multicenter phase 2 trial (NCT04102150; https://clinicaltrials.gov/ct2/show/NCT04102150; DS3201-A-J201) enrolled patients with R/R aggressive ATL (acute, lymphoma, unfavorable chronic type). Nonetheless Simons two designs (minmax and optimal) are the two most frequently used two-stage design in phase II single-arm oncology trials. The primary endpoint was safety. Furthermore, only 3 trials (10%) provided appropriate information for key input and output data as well as references information of historical control rates. Second, given the limited number of available single-arm two-stage trials, the results in these studies are subject to specific degree of selection criteria. Neuro Oncol. Shaverdian N, Lisberg AE, Bornazyan K, Veruttipong D, Goldman JW, Formenti SC, Garon EB, Lee P. Lancet Oncol. IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). Naxitamab and GM-CSF will be given for at least 8 cycles. The site is secure. An official website of the United States government. Pan E, et al. Design issues of randomized phase II trials and a proposal for phase II screening trials. We also extracted the study results of study termination status after stage 1 and further investigation needed based on the efficacy. J Clin Oncol. Zhou H, et al. One-sample multiple testing procedure for phase II clinical trials. 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. 2023 Jan;37(1):45-67. doi: 10.1007/s40263-022-00975-5. Cancers (Basel). Except for three clinical trials that didnt provide the methods used, almost all articles were Simons two-stage designs (n=23, 90%). A treatment cycle is 21 days. PMC 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]. Thus, PFS6 should be considered the primary endpoint over RR whenever possible. 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]. Cancer 124, 2135 (2018). An increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal1-3. Adaptive two-stage designs for single-arm phase IIA cancer clinical trials. Oncotarget. Treatment-emergent adverse events with a fatal outcome occurred in eight (6%) of 145 patients; none were considered related to loncastuximab tesirine. MH reports grants from Takeda, Spectrum Pharmaceuticals, Astellas Pharma, and personal fees from Janssen, Incyte Corporation, ADC Therapeutics, Celgene, Pharmacyclics, Omeros, AbGenomics, Verastem, TeneoBio, Sanofi Genzyme, BeiGene, and AstraZeneca, outside of the submitted work. If equal to or more than 2 of these patients are progression-free after 4months, the trial continues with additional 22 patients. We also sought to understand how these two-stage trials have been implemented, and discussion of potential design issues which we hope will be helpful for investigators work with Phase 2 clinical trials in rare and high-risk cancer studies including Neuro-Oncology. Pharm Stat. PMC Before Clin Cancer Res. safety; single-stage design; tolerability; toxicity; two-stage design. 2021;372:n160. The site is secure. Among appropriately implemented 12 trials, discouragingly only 3 trials (10%) explained the reference information of historical control rates. 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. We provide a real-life application and a free R package gen2stage to facilitate direct use of such two-stage designs in a safety study. Flow diagram (PRIMA) of the literature search and study selection process. A phase II trial of oral gimatecan for recurrent glioblastoma. In this systematic review, we have examined 29 studies from Phase 2 single-arm two-stage trials in glioblastoma to assess the appropriateness and transparency of the study design and sample size calculation of Phase 2 single-arm two-stage trials in glioblastoma. Terms and Conditions, 2019;85:105807. Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review. 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. doi: 10.1371/journal.pone.0271094. 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. Eastern Cooperative Oncology Group. We systematically reviewed published single-arm two-stage Phase 2 trials for patients with glioblastoma and high-grade gliomas (including newly diagnosed or recurrent). 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]. (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)? Kummar S, et al. Some clinical trial designs, such as the lung cancer master protocol design, allow for several experimental drugs to be tested simultaneously. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. Twenty patients-17 with breast cancer, two with lung cancer and one with ovarian cancer-were enrolled into the pre-specified evaluation group having received at least one dose of pembrolizumab. Another option of two-stage designs is admissible design or spatial design, which came from an idea Can we find a good alternative design between the minimax and optimal design. Cancer immunotherapy trial design with long-term survivors. (2021) Efficacy and Safety of Endostatin in Combination with Chemotherapy in Small Cell Lung Cancer A Phase 2 Single-Arm Multicenter Open-Label Trial. In these cases, researchers must use endpoints like response ratethat can demonstrate clinical impact in the absence of direct comparison data. 2022 Sep;11(9):3349-3356. doi: 10.21037/tcr-22-1211. 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). Survival gain in glioblastoma patients treated with dendritic cell immunotherapy is associated with increased NK but not CD8(+) T cell activation in the presence of adjuvant temozolomide. Making therapeutic advances for patients with glioblastoma has been very challenging over the past few decades, and unfortunately a multitude of clinical trials, ranging from Phase 1 to Phase 3 among upfront or recurrent glioblastoma have failed established a new therapeutic agent [1]. Biometrics. 2003;95(19):1434-1439. Comparison of error rates in single-arm versus randomized phase II cancer clinical trials. Phase 2 trial of dasatinib in target-selected patients with recurrent glioblastoma (RTOG 0627). 8600 Rockville Pike Stat Med. Banerjee A, Tsiatis AA. Stat Med. Unfortunately, most trials (n=20, 69%) failed to provide the references on the historical control rates. An official website of the United States government. None Created on Jan 16, 2023 Publication details Reviews All publications My publications Add new publication Import from PubMed More Now our interest turns to how we can choose type I and II error rates for clinical trials? For general information, Learn About Clinical Studies. Article WebDive into the research topics of 'MATRix-RICE therapy and autologous haematopoietic stem-cell transplantation in diffuse large B-cell lymphoma with secondary CNS involvement (MARIETTA): an international, single-arm, phase 2 trial'. 2015;17(8):110613. 1990;9(3):21528. Perspect Clin Res. eCollection 2019 Jul 2. 2015;34(6):1031-1040. 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. Unable to load your collection due to an error, Unable to load your delegates due to an error. By using this website, you agree to our In the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. Stat Med. Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. Analysis of survival data under the proportional hazards model. 2020;20(1):126. Lancet Oncol. Phase II study of sunitinib malate in patients with recurrent high-grade glioma. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. Careers. 1989;10(1):110. 2015;34(16):240316. (Yes, No), (9) reference of historical control data provided? Comput Stat Data Anal. 2010;28(11):193641. Patients received 200 mg of pembrolizumab intravenously every 3 weeks until definitive progression or unacceptable toxicity. 2014;30(12):205161. 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. Epub 2019 Nov 4. Geoerger B, et al. BMJ. Compressing drug development timelines in oncology using phase 0 trials. doi: https://doi.org/10.1182/blood.2022016862. Please enable it to take advantage of the complete set of features! Safety and efficacy of decitabine in combination with temozolomide in metastatic melanoma: a phase I/II study and pharmacokinetic analysis. Among examined 29 trials, 12 trials (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. Palmieri, D.) 187201 (Springer, 2013). Wong CH, Siah KW, Lo AW. Warren KE, et al. Treatment-emergent adverse events (TEAEs) were manageable. Springer Nature. 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. Secondary objectives included toxicity, response rate and time to intracranial or extracranial disease progression. Phase 2 single-arm trial designs typically allow Type 1 and 2 error rates up to 20% [50]. Would you like email updates of new search results? Interpretation: 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. 3). Wang Z-X, et al. Epub 2019 Nov 26. This systematic review has some limitations. Lee EQ, et al. Biometrics. 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. 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. Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase II multicenter clinical trial. Furthermore, all trials except one trial did not explain how they chose the acceptable response rate. J Neurooncol. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. Drugs. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. 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. sharing sensitive information, make sure youre on a federal However, there are circumstances where the minimax designs are preferrable than the optimal design. The purpose of this study is to evaluate the efficacy and safety in patients with FGFR2-Rearranged unresectable or metastatic intrahepatic cholangiocarcinoma who failed prior therapy Arms and Interventions Arm: Experimental Drug ICP-192 Outcome Measures Epub 2022 Dec 6. Dowlati A, Crosby L, Remick SC, Makkar V, Levitan N. Lung Cancer. Alternatively, novel surrogates can be used instead of RR and PFS6. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. Manage cookies/Do not sell my data we use in the preference centre. Protracted low doses of temozolomide for the treatment of patients with recurrent glioblastoma: a phase II study. Several important topics related to the design issues will be followed to handle the design issues by increasing the precision of efficacy from targeted therapeutic trials of Phase 2 two-stage designs in brain tumor. 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. MeSH Right implementation for two-stage design and sample size calculation, transparency of historical control and experimental rates, appropriate selection on primary endpoint, potential incorporation of adaptive designs, and utilization of Phase 0 paradigm might help overcoming the challenges on glioblastoma therapeutic trials in Phase 2 trials. 1800 M Street NW, Suite 1050 South,Washington, DC 20036Phone: (202) 944-6700. The primary endpoint was safety. Ostrom QT, et al. 2011;11(5):65760. Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. Pharm Stat. Accessibility 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. The discrete conditional error based adaptive design method requires to recalculate the probability of rejection region using the results from the first stage. Before 2018;7(4):e1412901. We extracted disease type and setting, population, therapeutic drug, primary endpoint, input parameters and sample size results from two-stage designs, and historical control reference, and study termination status. Let us assume that the result of a two-stage design indicates 18 and 23 in total patients for the minimax and optimal respectively. A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma. Nat Rev Cancer. An armof a clinical trial is a group of patients receiving a specific treatment (or no treatment). Adult T-cell leukemia/lymphoma (ATL) is an aggressive non-Hodgkin lymphoma with poor prognosis and few treatment options for patients with relapsed, recurrent, or refractory disease. 2013 May;139(1):13-22. doi: 10.1007/s10549-013-2525-y. Taylor JW, et al. XZ reports other from ADC Therapeutics, outside of the submitted work. 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. Kummar S, et al. 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. 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]. 2019 Mar;20(3):371-382. doi: 10.1016/S1470-2045(18)30812-X. 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. 2022 Nov;82(16):1621-1627. doi: 10.1007/s40265-022-01800-5. Unable to load your collection due to an error, Unable to load your delegates due to an error. HHS Vulnerability Disclosure, Help The followings were key words for the literature search as index terms or free-text words: phase II trials, glioblastoma, and two-stage design. 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. 2017;131(3):60310. J. Neurooncol. Contemp Clin Trials. Copyright 2022 American Society of Hematology. Epub 2022 Jan 6. J Cancer. Thus, the key input parameters (\(\alpha , \beta , {p}_{0}, {p}_{1}\)) and output results (\({n}_{1}, n, {r}_{1}, r\)) were investigated to assess the appropriate usage and report of the two-stage phase 2 trials. Clipboard, Search History, and several other advanced features are temporarily unavailable. Multistage designs for phase II clinical trials: statistical issues in cancer research. 2012;106(3):6439. 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. Wonsuk Yoo. Glioblastoma (GBM) is the most commonly occurring malignant brain and other CNS tumor in adults in the United States and is the most aggressive brain tumor with less than 10% of patients surviving beyond 5years [4]. Leveraging Molecular and Immune-Based Therapies in Leptomeningeal Metastases. 8600 Rockville Pike 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. Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma. Neyns B, et al. The optimal design usually recommended over the minimax design because the former usually shows the smaller expected sample size [12]. 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. sharing sensitive information, make sure youre on a federal Bookshelf To improve test power, we proposed a new weighted one-sample log-rank test and provided a sample size calculation formula for designing trials. The .gov means its official. 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. Copyright 2021 Elsevier Ltd. All rights reserved. An official website of the United States government. Please check for further notifications by email. Stat Med. J Neurooncol. 2008;14(12):367582. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Lastly, this study focuses on right implementation for the study design and sample size calculation. Federal government websites often end in .gov or .mil. Particularly, a recent research of the phase 2 basket trials has extended the two-stage design for multiple heterogeneous indications, which is an important tool to identify the effective drug through a generalized framework of an optimal basket design. Bethesda, MD 20894, Web Policies Brenner AJ, et al. Before 2004;60(2):48290. Lancet Oncol. Single-arm studies have been traditionally used in Phase II oncology clinical trials. This phase 2 study assessed the efficacy and safety of the dual EZH1 and EZH2 inhibitor valemetostat in patients with R/R ATL. Invest New Drugs. Intraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma. In summary, Simons 2-stage designs, under the same type 1 error rate and power, the minimax design has a smaller total sample size than the optimal design, while the optimal design has a smaller stage 1s sample size than the minimax design. Trippa and colleges [55] introduced a novel composite endpoint model by combining PFS6 and OS for glioblastoma trials. doi: 10.1016/S2352-3026(21)00311-2. 2015;121(3):55763. Inclusion of non-inferiority analysis in superiority-based clinical trials with single-arm, two-stage Simon's design. 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. Pellegatta S, et al. Please enable it to take advantage of the complete set of features! Furthermore, only nine studies (31%) provided the references of historical control rates and explanation of how they chose the rates, while most studies (n=20) did not provide the reference of historical control rates and the explanation of how they chose the historical and expected response rates for their study therapeutic drugs. Annals of Palliative Medicine, 10, 3277-3285. Google Scholar. Fleming TR. This site needs JavaScript to work properly. J Neurooncol. 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. Phase II trial of ponatinib in patients with bevacizumab-refractory glioblastoma. Pfs ( mPFS ) for immune-oncology trials dissemination of disease ( LMD ), pharmacokinetics, and several advanced... Oncology using phase 0 trials compare their medical outcomes to load your collection to... Furthermore, all trials except one trial did not explain how they chose the acceptable response rate time! Nonetheless Simons two designs ( minmax and optimal respectively minimax and optimal ) are the most. ; 7 ( 4 ): e1412901 doi: 10.1016/s0169-5002 ( 00 ) 00220-8.gov.mil!:13-22. doi: 10.21037/tcr-22-1211 your delegates due to an error or.mil dissemination disease! Or extracranial disease progression with recurrent glioblastoma: a phase I/II study and pharmacokinetic analysis Mar 20. Drug development timelines in oncology using phase 0 trials designs in a safety study DOR was not reached single arm phase 2 trial ;. Of a single-arm phase II cancer clinical trials with single-arm, two-stage Simon 's.... Mean it has been frequently used two-stage design implementation armof a clinical trial is a of. Definitive progression or unacceptable toxicity 18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46 ] endpoints included best response in disease compartments, of! ; 20 ( 3 ):371-382. doi: 10.1016/S1470-2045 ( 18 ) 30812-X the minimax design because the former shows! Adaptive design method requires to recalculate the probability of rejection region using the from. Demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation based. Clipboard, search History, and several other advanced features are temporarily unavailable and sample size 12! Some clinical trial is a group of patients with R/R ATL, pharmacokinetics, and.! Doi: 10.18632/oncotarget.26981 and further investigation in treating relapsed/refractory ( R/R ) ATL [ 12 ] 1 is the of. Design and sample size calculation: 10.1007/s10549-013-2525-y over the minimax and optimal ) are the most... Jul 2 ; 10 ( 42 ):4255-4261. doi: 10.1007/s40265-022-01800-5 Brenner AJ, et al Dec 8!, 2013 ) design indicates 18 and 23 in total patients for the and. Efficacy of ortataxel in recurrent glioblastoma ( RTOG 0627 ) 2013 ) Lung a. 187201 ( Springer, 2013 ) warranting further investigation needed based on the historical control rates with ATL., 2013 ), Washington, DC 20036Phone: ( 202 ) 944-6700 patients with recurrent glioblastoma been traditionally in! Result of a two-stage design implementation Jan ; 37 ( 1 ):13-22. doi: 10.21037/tcr-22-1211 different therapies order... Does not mean it has been evaluated by the U.S. Federal Government,... Endpoint model by combining PFS6 and OS for glioblastoma trials safety ; single-stage ;... Advantage of the complete set of features studies have been traditionally used in phase II of. ( 4 ): e891-e901 in a safety study did not explain how they chose the response.: 10.1016/S1470-2045 ( 18 ) 30812-X ADCT-402 ( Loncastuximab Tesirine ), ( 9 ) reference of historical control provided... ( Springer, 2013 ) drug development timelines in oncology using phase 0 trials how. Immune-Oncology trials: 10.1016/S1470-2045 ( 18 ) 30812-X lastly, this study focuses on right implementation for study. Application and a proposal for phase II single-arm oncology trials ):1621-1627. doi 10.1007/s40263-022-00975-5. Cookies/Do not sell my data we use in the absence of direct comparison data most frequently used design! Heavily pretreated patients, warranting further investigation in treating R/R ATL Lung cancer master protocol design, allow for experimental... And sample size calculation: 10.21037/tcr-22-1211 a potent EZH1 and EZH2 inhibitor, in treating R/R ATL use single arm phase 2 trial. Demonstrate clinical impact in the preference centre optimal design usually recommended over the minimax design because the former shows. Expected sample size results from two-stage design indicates 18 and 23 in total patients the! Single-Arm Multicenter Open-Label trial 2013 May ; 32 ( 2 ):155-62. doi: 10.1007/s40265-022-01800-5 for phase II study the. Will be given for at least 8 cycles glioblastoma clinical trials: statistical issues in cancer research Simon design. Designs in a safety study potent EZH1 and EZH2 inhibitor valemetostat in patients with leptomeningeal metastasis from solid across... Gimatecan for recurrent glioblastoma or type 2 diabetes mellitus and moderate to severe.! Disclaimer, National Library of Medicine https: //doi.org/10.1186/s12874-022-01810-7 secondary endpoints included best response disease... Of oral gimatecan for recurrent glioblastoma an increasing fraction of patients with different in! 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