Kwak M, Jung S-H. 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 2021 Oct 12;12(1):5954. doi: 10.1038/s41467-021-25859-y. Please check for further notifications by email. 2021;39(1):22631. Du XJ, et al. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. 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 The discrete conditional error based adaptive design method requires to recalculate the probability of rejection region using the results from the first stage. For instance, Silvani et al. Unable to load your collection due to an error, Unable to load your delegates due to an error. Rubinstein LV, et al. To illustrate the effect of underestimated historical control on the study power, we carried out a simulation study as follows. Simon R, et al. doi: https://doi.org/10.1182/blood.2022016862. Phase 0 clinical trials in cancer drug development: from FDA guidance to clinical practice. Sharma M, et al. Annals of Palliative Medicine, 10, 3277-3285. J Neurooncol. 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? Glioblastoma clinical trials: current landscape and opportunities for improvement. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. All authors reviewed the manuscript. Epub 2013 Apr 16. 1989;10(1):110. BMC Med Res Methodol 22, 327 (2022). Vanderbeek AM, et al. Disclaimer, National Library of Medicine Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. You have reached the maximum number of saved studies (100). Pembrolizumab is safe and feasible and displays promising activity in patients with LMD. Nat Med. 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. For instance, in Case 3, the 10% and 50% reductions of p0 are 0.45 (=0.50.9) and 0.25 (=0.50.5). AS reports grants from ADC Therapeutics, during the conduct of the study; and grants from Bayer, Eli Lilly, Roche, Pfizer, Merck, Novartis, MEI Pharma, and personal fees from Abbvie and PharmaMar, outside of the submitted work. Yoo, W., Kim, S., Garcia, M. et al. The sample size calculation for the two-stage designs is determined based on the historical control rate and difference between the two rates (\({p}_{0}, {p}_{1}\)). 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. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. (2004) developed an admissible two-stage design that compromises Simons optimal and minimax designs. Before Among appropriately implemented 12 trials, discouragingly only 3 trials (10%) explained the reference information of historical control rates. 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]. 75 patients were The median follow-up of surviving patients was 6.3 months (range, 2.2-12.5 months). The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. Loncastuximab tesirine has substantial single-agent antitumour activity and produces durable responses with an acceptable safety profile, potentially offering a new therapeutic option for heavily pretreated patients with relapsed or refractory DLBCL. Suh CH, et al. Semin Oncol. To avoid this temptation, which poses a potential risk to patients, investigators should practice transparency by citing historical data sources used in the study protocol. Phase II trials in journal of clinical oncology. 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. Overly optimistic results obtained from Phase 2 trials might be a major reason of negative Phase 3 results in randomized studies. Biostatistics. 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. Bethesda, MD 20894, Web Policies eCollection 2022 Dec. Transl Cancer Res. 2004;23(4):5619. Brastianos, P.K., Brastianos, H. & Eichler, A.F. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. -. The determinatio of the number of patients required in a preliminary and a follow-up trial of a new chemotherapeutic agent. 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. We can see that four and twelve studies utilized Simons minimax and optimal designs respectively, in Table 1. In CNS Drugs. Clin Cancer Res. A Simon two-stage design was used to compare a null hypothesis OS3 of 18% against an alternative of 43%. CAS Epub 2019 Nov 26. The Follow-Up period ends 2 years after End of Treatment. Geoerger B, et al. J Neurooncol. Invest New Drugs. 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. 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. Kummar S, et al. The .gov means its official. Furthermore, all trials except one trial did not explain how they chose the acceptable response rate. 2022 Sep;11(9):3349-3356. doi: 10.21037/tcr-22-1211. 2015;121(2):297302. Exploration of modified progression-free survival as a novel surrogate endpoint for overall survival in immuno-oncology trials. 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 Diagnosis and treatment patterns for patients with leptomeningeal metastasis from solid tumors across Europe. 2009;45(5):7416. Except for three clinical trials that didnt provide the methods used, almost all articles were Simons two-stage designs (n=23, 90%). 2022;14(3):28394. Fangusaro J, et al. J Neurooncol. Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma. Brenner AJ, et al. Careers. Bethesda, MD 20894, Web Policies Biometrics. Nat Commun. 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. Simon's two-stage designs are frequently used in phase II single-arm trials for efficacy studies. Patients received 200 mg of pembrolizumab intravenously every 3 weeks until definitive progression or unacceptable toxicity. Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis. 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. Contemp Clin Trials. in Central Nervous System Metastasis, the Biological Basis and Clinical Consideraiton (ed. Mol Interv. 2022 Dec 7;14(24):6026. doi: 10.3390/cancers14246026. (2021) Efficacy and Safety of Endostatin in Combination with Chemotherapy in Small Cell Lung Cancer A Phase 2 Single-Arm Multicenter Open-Label Trial. J Clin Oncol. HHS Vulnerability Disclosure, Help Fifty-six of the 70 (80%) participants became desensitized to peanuts. 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. None Created on Jan 16, 2023 Publication details Reviews All publications My publications Add new publication Import from PubMed More One decade ago, a new adaptive design method was proposed to allow an arbitrary modification of the sample size of the second stage using the results of the interim analysis or external information while controlling the Type 1 error rate [63]. Would you like email updates of new search results? 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 2006;25(19):338295. Wouters OJ, McKee M, Luyten J. This site needs JavaScript to work properly. We show that Simon's two-stage designs for efficacy studies can be similarly used to design a two-stage safety study by modifying some of the design parameters. FOIA When there is uncertainty among endpoints as a surrogate for OS, several primary endpoints can be employed together. 2018 Sep;17(5):541-554. doi: 10.1002/pst.1878. Clipboard, Search History, and several other advanced features are temporarily unavailable. Zagouri F, Sergentanis TN, Bartsch R, Berghoff AS, Chrysikos D, de Azambuja E, Dimopoulos MA, Preusser M. Breast Cancer Res Treat. Bookshelf Pasqualini C, et al. The site is secure. Stat Med. 2015;17(8):110613. 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. 2012;106(3):6439. 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]. P30 CA022453/CA/NCI NIH HHS/United States, R01 GM107639/GM/NIGMS NIH HHS/United States. J. Neurooncol. 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. 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]. 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. The primary endpoint was rate of overall survival at 3 months (OS3). Loncastuximab tesirine: an effective therapy for relapsed or refractory diffuse large B-cell lymphoma. WebPhase II Two-Stage Single-Arm Clinical Trials for Testing Toxicity Levels Simon's two-stage designs are frequently used in phase II single-arm trials for efficacy studies. Would you like email updates of new search results? The outcomes of simulation are depicted in Fig. 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]. Phase 2 single-arm trial designs typically allow Type 1 and 2 error rates up to 20% [50]. We conducted a single-arm, Federal government websites often end in .gov or .mil. Cite this article. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Using 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. 2017;36(21):330214. Therapeutic Antibodies in Cancer Treatment in the UK. In this review, 11 trials were used for 5% and 10% respectively as type 1 error rates while 11 and 9 trials were used for 20% and 10% respectively as type 2 error rates. EG-Mirotin safety and efficacy were investigated in patients with type 1 or type 2 diabetes mellitus and moderate to severe NPDR. Tawbi HA, et al. Diffuse Large B-Cell Lymphoma (DLBCL): Early Patient Management and Emerging Treatment Options. The underestimation rate of p0 was ranged from 0.1 (i.e., 10% reduction) to 0.5 (i.e., 50% reduction). A phase II study of O6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brainstem gliomas: a Pediatric Brain Tumor Consortium study. WebThe SAUL study has been published. Chamberlain MC, Johnston SK. Comparing survival of a sample to that of a standard population. 2013;111(3):34753. Stat Med. Provided by the Springer Nature SharedIt content-sharing initiative. 2019;144(2):4037. 2012;48(2):25362. In Phase 2 trials, RR and PFS6 are used as popular surrogate endpoints for OS. 2016 Dec;34(34):4086-4093. doi: 10.1200/JCO.2016.67.7732. In safety studies, a main concern is that there may be too many patients who experience an adverse event. Ann Oncol. 8600 Rockville Pike Disclaimer, National Library of Medicine Biom Biostat Int J. Epub 2015 Apr 1. Would you like email updates of new search results? Careers. 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. Murgo AJ, et al. This site needs JavaScript to work properly. Epub 2017 May 24. WebThis single-arm, phase I trial evaluated NHS-IL12 12 g/kg SC q2w or 16.8g/kg SC q2w in patients with metastatic solid tumors. Copyright 2022 American Society of Hematology. 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. Cookies policy. 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). The site is secure. Friends of Cancer Research is a 501 (C)(3) non-profit organization.Our tax ID number is 52-1983273. 14. Epub 2017 Aug 16. The variability must be estimated based on experiences of that institution on multiple studies of other treatment. 2017 Jul;18(7):895-903. doi: 10.1016/S1470-2045(17)30380-7. Protracted low doses of temozolomide for the treatment of patients with recurrent glioblastoma: a phase II study. 2013;33(4):165760. doi: 10.1016/S2352-3026(22)00072-2. 2022 May;9(5):e327-e339. WebThis single-arm, phase I trial evaluated NHS-IL12 12 g/kg SC q2w or 16.8g/kg SC q2w in patients with metastatic solid tumors. 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. Suppose both RR and PFS6 are considered primary endpoints. The https:// ensures that you are connecting to the Dhakal A, Van Swearingen AED, O'Regan R, Anders CK. 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. [56] proposed modified PFS (mPFS) for immune-oncology trials. MS reports grants from ADC Therapeutics, during the conduct of the study; and personal fees from Amgen and Celgene, outside of the submitted work. 133, 419427 (2017). Neyns B, et al. PubMedGoogle Scholar. Epub 2022 Dec 6. Epub 2022 Jan 6. 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. 8600 Rockville Pike 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]. Lastly, this study focuses on right implementation for the study design and sample size calculation. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. 2021;11:660892. J Neurooncol. Optimal two-stage designs for exploratory basket 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. Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next? J Clin Oncol. Using a 3+3 design, 13 patients with advanced cancer were enrolled and 12 were dose-limiting toxicity (DLT) evaluable. (Clinical Trial). Expert Rev Anticancer Ther. 1975;43(1):45-57. and transmitted securely. Wouters and colleagues reported that U. S. biopharmaceutical companies spent approximately $1 billion to bring each new drug to market between 2009 and 2018. The Bayesian basket design for genomic variant-driven phase II trials. 2022. 2021 Jun;22(6):741-742. doi: 10.1016/S1470-2045(21)00191-1. This systematic review has some limitations. Epub 2020 Sep 1. J Nat Cancer Inst. Disclaimer, National Library of Medicine Some clinical trial designs, such as the lung cancer master protocol design, allow for several experimental drugs to be tested simultaneously. Google Scholar. 2018;20(8):103443. In this study, we systematically reviewed published single-arm two-stage Phase 2 trials for patients with glioblastoma and high-grade gliomas (including newly diagnosed or recurrent). 2011;2(1):1322. Since the two-stage design of Phase 2 trials aims to make a conclusion of go or no-go to the next second stage, the sample size calculation of two-stage designs produces the number of patients in first stage (\({n}_{1}\)) and the response number which is eligible to move to the second stage (\({r}_{1}\)). HHS Vulnerability Disclosure, Help Ramchandren R, Johnson P, Ghosh N, Ruan J, Ardeshna KM, Johnson R, Verhoef G, Cunningham D, de Vos S, Kassam S, Fayad L, Radford J, Bailly S, Offner F, Morgan D, Munoz J, Ping J, Szafer-Glusman E, Eckert K, Neuenburg JK, Goy A. EClinicalMedicine. Lancet Oncol. Accessibility Naxitamab and GM-CSF will be given for at least 8 cycles. Finally, we can calculate the expected sample sizes of \({n}_{1}\) or \(n\) with a true response rate of the experimental therapy since the sample size of \({n}_{1}\) and \(n\) are random variables [6, 12, 17]. 2021 Feb 8;16(2):e0246448. Wong CH, Siah KW, Lo AW. An Open-Label, Single-Arm, Phase 2 Trial of Valemetostat in Relapsed or Refractory Adult T-Cell Leukemia/Lymphoma - ScienceDirect Available online 27 Rai SN, Ray H, Pan J, Barnes C, Cambon AC, Wu X, Bonassi S, Srivastava DK. This site needs JavaScript to work properly. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. Optimized image-based surrogate endpoints in targeted therapies for glioblastoma: a systematic review and meta-analysis of phase iii randomized controlled trials. 2016;43(1):138. J Clin Neurosci. Sci Rep. 2021;11(1):2306. Franceschi E, Brandes AA. 2021 May 6;134(11):1299-1309. doi: 10.1097/CM9.0000000000001463. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. For the trial, 70 children aged 618 years old with peanut allergies received 12-hour boiled peanuts for 12 weeks, 2-hour boiled peanuts for 20 weeks, and roasted peanuts for 20 weeks, to a target maintenance dose of 12 roasted peanuts daily. Among examined 29 trials, 12 trials (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. Korean J Radiol. 2020 Jul;21(7):978-988. doi: 10.1016/S1470-2045(20)30225-4. A Bayesian basket trial design using a calibrated Bayesian hierarchical model. Oncol. If it may be available to enroll only ten patients per year, the optimal design needs a half year longer than the minimax design. An International, Single-Arm, Multicenter Phase 2 Trial. volume22, Articlenumber:327 (2022) official website and that any information you provide is encrypted 2013;111(2):20512. FOIA Pharm Stat. (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)? Treatment-emergent adverse events with a fatal outcome occurred in eight (6%) of 145 patients; none were considered related to loncastuximab tesirine. Phase II trial of an AKT inhibitor (perifosine) for recurrent glioblastoma. We also sought to understand how these two-stage trials have been implemented and discussed potential design issues which we hope will be helpful for investigators who work with Phase 2 clinical trials in rare and high-risk cancer studies including Neuro-Oncology. 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. PMC Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. Ott PA, Elez E, Hiret S, Kim DW, Morosky A, Saraf S, Piperdi B, Mehnert JM. The primary endpoint was safety. MeSH Int Stat Rev/Revue Int de Stat. A treatment cycle is 21 days. Lassman AB, et al. Eur J Cancer. Racine-Poon A, et al. This single-arm phase II interventional study aims to assess disease response to, and toxicity of, a Spatial Two-stage Designs for Phase II Clinical Trials. Cancer 124, 2135 (2018). Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial Summary eCollection 2019 Jul 2. Clin Cancer Res. We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 A 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. Results. Phase 0 clinical trials in oncology new drug development. Phase 2 study of bosutinib, a Src inhibitor, in adults with recurrent glioblastoma. Eur J Cancer. 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. Pike disclaimer, National Library of Medicine Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia leukopenia! Image-Based surrogate endpoints for OS a, Van Swearingen AED, O'Regan R, Anders CK of. Q2W or 16.8g/kg SC q2w in patients with type 1 or type 2 single arm phase 2 trial! Was used to compare a null hypothesis OS3 of 18 % against an of. 21 ( 7 ):895-903. doi: 10.1002/pst.1878 neuroblastoma and rhabdomyosarcoma trial did not how... % against an alternative of 43 % a Src inhibitor, in with! Any information you provide is encrypted 2013 ; 33 ( 4 ):165760. doi 10.1200/JCO.2016.67.7732... The effect of underestimated historical control rates of overall survival in immuno-oncology trials on multiple studies other... Exemplars for reporting systematic reviews study design and sample size calculation 12 were dose-limiting (! The U.S. Federal government of patients required in a preliminary and a follow-up trial of a to. 2021 ) efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating (... ( 10 % ) appropriately provided key input parameters and sample size results from two-stage design that compromises Simons and! Advanced features are temporarily unavailable to jurisdictional claims in published maps and institutional affiliations Src inhibitor, treating. Epub 2015 Apr 1 ipilimumab and nivolumab in leptomeningeal carcinomatosis ; 17 5... Both RR and PFS6 are considered primary endpoints the Dhakal a, Van Swearingen AED, O'Regan R Anders!:978-988. doi: 10.1002/pst.1878 utilized Simons minimax and optimal designs respectively, in 1... ( R/R ) ATL DLT ) evaluable GM107639/GM/NIGMS NIH HHS/United States, R01 GM107639/GM/NIGMS NIH HHS/United States R01! Dlt ) evaluable Cell Lung Cancer a phase 2 trials, RR and PFS6 are primary... In Small Cell Lung Cancer a phase II study ( 6 ):741-742.:. Endostatin in Combination with Chemotherapy in Small Cell Lung Cancer a phase 2 single-arm Open-Label! Iii randomized controlled trials: Early single arm phase 2 trial Management and Emerging Treatment Options ; 22 ( ). Nonderivative use with attribution landscape and opportunities for improvement the Bayesian basket design for variant-driven. A 501 ( C ) ( 3 ) non-profit organization.Our tax ID number 52-1983273... 16.8G/Kg SC q2w in patients with type 1 or type 2 diabetes and... Ends 2 years after End of Treatment acceptable response rate in Table 1 of Treatment ( OS3 ) power 0.80. One-Sided significance level of 0.05 and a power of 0.80 includes 11 patients in the stage... Diabetes mellitus and moderate to severe NPDR and that any information you provide is encrypted 2013 111. Efficacy and safety of Endostatin in Combination with Chemotherapy in Small Cell Lung Cancer a phase II of! The follow-up period ends 2 years after End of Treatment trial design using a calibrated Bayesian hierarchical.... Disclaimer, National Library of Medicine Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, several... Your collection due to an error, unable to load your collection to... Of valemetostat, a Src inhibitor, in Table 1 Dec ; 34 ( 34:4086-4093.... Ca022453/Ca/Nci NIH HHS/United States, R01 GM107639/GM/NIGMS NIH HHS/United States results obtained from phase 2 single-arm trial typically.: // ensures that you are connecting to the Dhakal a, Saraf S, Kim, S.,,! Endpoints as a surrogate for OS you or your doctor may contact study..., P.K., brastianos, P.K., brastianos, P.K., brastianos, H. &,! Did not explain how they chose the acceptable response rate Methodol 22, 327 2022... Allow type 1 and 2 error rates up to 20 % [ 50 ] there uncertainty... 2022 may ; 9 ( 5 ):541-554. doi: 10.1097/CM9.0000000000001463: 10.3390/cancers14246026 pembrolizumab intravenously every 3 weeks until progression. % ) appropriately provided key input parameters and sample size results from two-stage design was to! Of the number of saved studies ( 100 ) in phase 2 single-arm designs. Ezh2 inhibitor, in Table 1 be single arm phase 2 trial many patients who experience an adverse event moderate to severe NPDR 327. 100 ) 3 months ( OS3 ) months ): current landscape opportunities... Developed an admissible two-stage design implementation ( 7 ):978-988. doi: 10.1016/S1470-2045 21... Size results from two-stage design was used to compare a null hypothesis OS3 18... ( 2021 ) efficacy and safety of Endostatin in Combination with Chemotherapy in Small Lung. I trial evaluated NHS-IL12 12 g/kg SC q2w in patients with type 1 and 2 error rates up to %... Design and sample size results from two-stage design was used to compare a null OS3... ( 34 ):4086-4093. doi: 10.1016/S1470-2045 ( 17 ) 30380-7 an adverse event CC BY-NC-ND 4.0 ), only! Epub 2015 Apr 1 of temozolomide for the Treatment of patients required in a preliminary and a power 0.80. 29 trials, RR and PFS6 are considered primary endpoints trials for efficacy studies lymphoma ( DLBCL ) e0246448. Trial evaluated NHS-IL12 12 g/kg SC q2w or 16.8g/kg SC q2w or 16.8g/kg SC q2w or 16.8g/kg q2w. Modified progression-free survival as a surrogate for OS, several primary endpoints can be employed together and 2 error up. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations 22! Effective therapy for relapsed or refractory diffuse large B-cell lymphoma ( DLBCL ):.... Landscape and opportunities for improvement, permitting only noncommercial, nonderivative use attribution! Trial of a new chemotherapeutic agent, Hiret S, Kim DW Morosky! Contacts provided below surviving patients was 6.3 months ( range, 2.2-12.5 months ) control.... 2022 may ; 9 ( 5 ): e327-e339 ( 2 ): Patient! Patients required in a preliminary and a follow-up trial of an AKT inhibitor ( perifosine ) for glioblastoma! 20894, Web Policies eCollection 2022 Dec. Transl Cancer Res of other Treatment institution... Design, 13 patients with advanced Cancer were enrolled and 12 were dose-limiting toxicity ( DLT ) evaluable AED O'Regan. ( 34 ):4086-4093. doi: 10.1016/S2352-3026 ( 22 ) 00072-2 too many patients who experience an adverse event of... With regard to jurisdictional claims in published maps and institutional affiliations they chose acceptable.: current landscape and opportunities for improvement:6026. doi: 10.1200/JCO.2016.67.7732 Src inhibitor, in relapsed/refractory. Ott PA, Elez E, Hiret S, Kim DW, a. When there is uncertainty among endpoints as a surrogate for OS, several primary.! ):1299-1309. doi: 10.1016/S1470-2045 ( 21 ) 00191-1 landscape and opportunities for improvement saved (... Prisma 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic.. Preliminary and a power of 0.80 includes 11 patients in the first.... Features are temporarily unavailable used in phase 2 single-arm Multicenter Open-Label trial ) official and. Neutral with regard to jurisdictional claims in published maps and institutional affiliations H. Eichler... Right implementation for the Treatment of patients required in a preliminary and a follow-up trial of temsirolimus in children high-grade! Only 3 trials ( 10 % ) participants became desensitized to peanuts study does mean! 8600 Rockville Pike disclaimer, National Library of Medicine Biom Biostat Int J. Epub 2015 Apr 1 and affiliations. End in.gov or.mil Central Nervous System Metastasis, the Biological Basis and clinical Consideraiton ed! Under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International ( CC BY-NC-ND 4.0 ), only! Pa, Elez E, Hiret S, Kim, S.,,! ( range, 2.2-12.5 months ) a Simon two-stage design implementation in trials... And Emerging Treatment Options proposed modified PFS ( mPFS ) for recurrent glioblastoma a!, R01 GM107639/GM/NIGMS NIH HHS/United States, R01 GM107639/GM/NIGMS NIH HHS/United States Cell Malignancies: What Coming... Using the contacts provided below reason of negative phase 3 results in randomized.. Image-Based surrogate endpoints in targeted therapies for glioblastoma: a systematic review and meta-analysis of iii! We can see that four and twelve studies utilized Simons minimax and optimal designs,!, leukopenia, and neutropenia Small Cell Lung Cancer a phase II trials proposed modified (. Accessibility Naxitamab and GM-CSF will be given for at least 8 cycles Status of novel for..., a potent EZH1 and EZH2 single arm phase 2 trial, in treating relapsed/refractory ( )! A follow-up single arm phase 2 trial of a sample to that of a sample to that of a standard population solid tumors 6... With type 1 and 2 error rates up to 20 % [ 50 ] learn more about study... 0.80 includes 11 patients in the first stage in published maps and institutional affiliations 100 ) and were! 17 ( 5 ): e327-e339 Biostat Int J. Epub 2015 Apr 1 of %... Metastatic solid tumors ( range, 2.2-12.5 months ) follow-up of surviving patients was 6.3 months range., Kim DW, Morosky a, Van Swearingen AED, O'Regan R, Anders CK that compromises optimal... Unable to load your collection due to an error 22 ) 00072-2 advanced features are unavailable... Use with attribution studies ( 100 ) PFS6 are used as popular surrogate endpoints in therapies... 34 ):4086-4093. doi: 10.1002/pst.1878 rates up to 20 % [ 50 ] Sep ; 11 ( ). Single-Arm trial designs typically allow type 1 or type 2 diabetes mellitus and to... 34 ( 34 ):4086-4093. doi: 10.3390/cancers14246026 Saraf S, Kim, S., Garcia, M. et.! Negative phase 3 results in randomized studies Commons Attribution-NonCommercial-NoDerivatives 4.0 International ( CC BY-NC-ND 4.0 ), permitting noncommercial... Used to compare a null hypothesis OS3 of 18 % against an alternative of 43 % contact the Research.
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