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. Unable to load your collection due to an error, Unable to load your delegates due to an error. 2014;33(12):2004-2016. Phase II clinical trials with time-to-event endpoints: optimal two-stage designs with one-sample log-rank test. sharing sensitive information, make sure youre on a federal 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 Optimal, minimax and admissible two-stage design for phase II oncology clinical trials. 2005;23(28):7199206. In this research, we proposed a piecewise proportional hazards cure rate model with random delayed treatment effect to design single-arm phase II immunotherapy cancer trials. Perspect Clin Res. Lancet Oncol. 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. Batista MFFV, Eiriz I, Fitzpatrick A, Le Du F, Braga S, Alpuim Costa D. Breast Care (Basel). We can see that four and twelve studies utilized Simons minimax and optimal designs respectively, in Table 1. 2021;39(1):22631. PLoS One. The sample size calculation for the two-stage designs is determined based on the historical control rate and difference between the two rates (\({p}_{0}, {p}_{1}\)). Would you like email updates of new search results? Webmultiple myeloma: a multicenter, single-arm phase 2 trial Thilo Zander 1, Thomas Pabst 2, Smi Schr 3, Stefan Aebi 1,2, Ulrich Mey 4, Urban Novak2, Erika Lerch 5, Galle Rhyner Agocs 6, eCollection 2021. statement and 2019;85:105807. government site. The site is secure. BMJ. This site needs JavaScript to work properly. Two types of errors (\(\alpha , \beta\)) are key information for all study designs. Chamberlain MC, Johnston SK. Kieser M, Rauch G. Two-stage designs for cross-over bioequivalence trials. We enrolled patients aged 18 years with HER2-positive breast cancer and newly 75 patients were 2013;111(2):20512. Among 29 trials, only three has been completed for both stages and two studies have shown the efficacy. Regardless that more than 75% trials mentioned all key input parameters, many studies (17/29, 59%) failed to provide at least one key output of sample size calculation results of the number of samples of both stages (\({n}_{1}, n\)) and the treatment rejection numbers of the first stage and both stages (\({r}_{1}, r\)). (Yes, No), (8) all four output results of sample size appropriately reported? 2004;23(4):5619. Phase II study of Dovitinib in recurrent glioblastoma. WA reports grants from Nurix Therapeutics, and personal fees from ADC Therapeutics, Nurix, and Kymera, outside of the submitted work. The underestimation rate of p0 was ranged from 0.1 (i.e., 10% reduction) to 0.5 (i.e., 50% reduction). sharing sensitive information, make sure youre on a federal Therefore, the most deterministic input parameters for Phase 2 single-arm two-stage designs are unacceptable response rate (\({p}_{0}\)) of historical control and acceptable response rate (\({p}_{1}\)) of expected treatment. End of study was approximately 8 1 weeks (57 7 days) after the first drug administration. volume22, Articlenumber:327 (2022) This single-arm phase II interventional study aims to assess disease response to, and toxicity of, a Valemetostat 200 mg orally once Cancer immunotherapy trial design with long-term survivors. Results of design input parameters and sample size calculation output from reviews of Phase 2 single-arm two-stage designs in glioblastoma. (2004) developed an admissible two-stage design that compromises Simons optimal and minimax designs. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 2022 May;169:107420. doi: 10.1016/j.csda.2021.107420. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, 5R21CA220253-02/U.S. Lastly, this study focuses on right implementation for the study design and sample size calculation. Phase 0 clinical trials in oncology new drug development. 2014;1(2):345. 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 Pharm Stat. Designing phase 0 cancer clinical trials. Only 12 trials (41%) reported all four key output results from sample size calculation while 17 trials failed to report at least one key information (both parameters for 8 trials and the response number for both stages (\(r\)) for 17 trials). Would you like email updates of new search results? and transmitted securely. Cancer Med. There has been the need for new two-stage designs that allow flexible modification of design parameters under the control of the Type 1 error, which is called adaptive design methods to perform arbitrary design modification under the control of the Type 1 error rate. Eur J Cancer. Pasqualini C, et al. Suppose both RR and PFS6 are considered primary endpoints. and transmitted securely. All other rights reserved. Biostatistics. The https:// ensures that you are connecting to the and transmitted securely. Childs Nerv Syst. 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. Wouters OJ, McKee M, Luyten J. Patients received 200 mg of pembrolizumab intravenously every 3 weeks until definitive progression or unacceptable toxicity. 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]. 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. The rapid trials and ethical reasons generally lead the single-arm trials to be performed with interim analyses for possible early termination of the trials. Sharma M, et al. Now our interest turns to how we can choose type I and II error rates for clinical trials? Wu J, Pan H, Hsu CW. Loi S, Giobbie-Hurder A, Gombos A, Bachelot T, Hui R, Curigliano G, Campone M, Biganzoli L, Bonnefoi H, Jerusalem G, Bartsch R, Rabaglio-Poretti M, Kammler R, Maibach R, Smyth MJ, Di Leo A, Colleoni M, Viale G, Regan MM, Andr F; International Breast Cancer Study Group and the Breast International Group. The .gov means its official. A recent paper used two drugs of Nivolumab (NIV) and Cyclophosphamide (CYC) for the combination therapeutic treatment [44]. In the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. (Yes, No), (9) reference of historical control data provided? Phase II trial of an AKT inhibitor (perifosine) for recurrent glioblastoma. Manage cookies/Do not sell my data we use in the preference centre. Altwairgi AK, et al. 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. The primary endpoint was met with a centrally reviewed ORR of 48.0% (90% CI, 30.5% to 65.9%), including 5 complete and 7 partial remissions. 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. Before Epub 2022 Jan 6. Oncotarget. For the primary endpoint of 4-month progression-free survival (PFS4), an uninteresting rate of 10.9% obtained from historical controls and an anticipated rate of 28.9% were assumed. J Neurooncol. 2021;11:660892. Korean J Radiol. Epub 2019 Nov 26. 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]. Hematology Am Soc Hematol Educ Program. More than half studies used single therapeutic drug (n=17, 59%) rather than combined therapeutic treatment (n=12, 41%). HHS Vulnerability Disclosure, Help 2013;10(5):72034. ADC Therapeutics. Stat Med. 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. 2019 Mar;20(3):371-382. doi: 10.1016/S1470-2045(18)30812-X. eCollection 2019 Jul 2. Biometrics. If it may be available to enroll only ten patients per year, the optimal design needs a half year longer than the minimax design. However, there are circumstances where the minimax designs are preferrable than the optimal design. Eltarhoni K, Kamel F, Ihebunezie K, Nisar P, Soloviev M. Int J Mol Sci. The clinical trials landscape for glioblastoma: is it adequate to develop new treatments? IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). 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 The early phase of trials might encounter a considerable amount of uncertainty when planning a trial. We identified a total of 81 articles based on online search using Two-stage Phase II trials in glioblastoma. Third, when expected sample sizes from both designs are close each other, the minimax design may be more appropriate than the optimal design because the minimax design produces the smaller total patients [6]. Temozolomide (TMZ) was mostly used for combination therapeutic drugs (n=7 with pegylated liposomal doxorubicin (PLD), O6-benzylguanine (O6B), irinotecan (IRI), decitabine (DAC), Dendritic (DEN), Nintedanib (NIN), and Atorvastatin (ATO)) while Bevacizumab (BEV) was second mostly used for combination drugs (n=3 with temsirolimus (TEM), Ponatinib (PON), and Evofosfamide (EVO)). 14. Reference curve sampling variability in one-sample log-rank tests. Study design input information and output results from sample size calculation related to two-stage design implementation were examined. How low levels for both errors are low enough to be a good design? 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. Expert Rev Anticancer Ther. Biom Biostat Int J. 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. Lassen U, et al. 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. Nat Rev Cancer. 2011;11(5):65760. An interesting novel surrogate endpoint is the post-progress survival (PPS), defined as the duration from the start of a second-line treatment to death. doi: 10.1016/S2352-3026(22)00072-2. 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]. Figure1 shows flow diagram (PRIMA) of the literature search and study selection process. Lee EQ, et al. Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. In safety studies, a main concern is that there may be too many patients who experience an adverse event. 2004;60(2):48290. Would you like email updates of new search results? Brastianos, P.K., Brastianos, H. & Eichler, A.F. 2020 Mar 15;39(6):698-708. doi: 10.1002/sim.8440. Santoni M, et al. 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. Patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity. 2019;20(2):27386. An Open-Label, Single-Arm, Phase 2 Trial of Valemetostat in Relapsed or Refractory Adult T-Cell Leukemia/Lymphoma - ScienceDirect Available online 27 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 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. Bethesda, MD 20894, Web Policies Cookies policy. 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. 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 (\({r}_{1}, r\)). Results. WebSingle-dose carboplatin followed by involved-node radiotherapy for stage IIA and stage IIB seminoma (SAKK 01/10): a single-arm, multicentre, phase 2 trial Erstverffentlichung 2022 2017;131(3):60310. 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. 2013;111(3):34753. The era of CD19-directed therapy in diffuse large B-cell lymphoma. Design issues of randomized phase II trials and a proposal for phase II screening trials. Choosing to participate in a study is an important personal decision. You have reached the maximum number of saved studies (100). Stat Med. Clinical end points in recurrent glioblastoma: are antiangiogenic agents friend or foe? Epub 2020 Sep 1. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. 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. 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. Since the two-stage design of Phase 2 trials aims to make a conclusion of go or no-go to the next second stage, the sample size calculation of two-stage designs produces the number of patients in first stage (\({n}_{1}\)) and the response number which is eligible to move to the second stage (\({r}_{1}\)). In Oncol. 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. Pharm Stat. Phase 0 clinical trials in cancer drug development: from FDA guidance to clinical practice. 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). [56] proposed modified PFS (mPFS) for immune-oncology trials. 2020 Jul;21(7):978-988. doi: 10.1016/S1470-2045(20)30225-4. Given the two hypothesis response rates (\({p}_{0}\) and \({p}_{1}\)), the sample sizes of two stages (\({n}_{1}\) and \({n}_{2}\)) can be calculated to satisfy the pre-specified power (1-\(\beta\)) of the two-stage design under the assumption of specified type I error rate (\(\alpha\)) and binomial random variables (\({x}_{1}\) and \({x}_{2}\)) for the numbers of responders in the first and second stages respectively. Comparison of error rates in single-arm versus randomized phase II cancer clinical trials. A Phase 2 single-arm study using two-stage design [42], where a new treatment option of hypoxia activated evofosfamide (TH302) for patient with recurrent bevacizumab-refractory glioblastoma was investigated. 2018 Sep;17(5):541-554. doi: 10.1002/pst.1878. The median follow-up of surviving patients was 6.3 months (range, 2.2-12.5 months). 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. Such an unexpected situation cannot be appropriately handled with the current system of two-stage designs because current designs require to prespecify the design information like sample size for each stage and stopping rules in the study protocol. Banerjee A, Tsiatis AA. Single-arm studies have been traditionally used in Phase II oncology clinical trials. Jung et al. Neuro Oncol. https://doi.org/10.1186/s12874-022-01810-7, DOI: https://doi.org/10.1186/s12874-022-01810-7. J Neurooncol. A systematic review of surrogate endpoints (SEPs) for overall survival (OS) in metastatic colorectal cancer mCRC. There was no language restriction, but only complete papers published in peer-reviewed journals were considered. Simon R. Optimal two-stage designs for phase II clinical trials. J Neurooncol. HHS Vulnerability Disclosure, Help Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial Summary 1990;9(3):21528. Cite this article. 2022 Jul 21;17(7):e0271094. Ishida T, Fujiwara H, Nosaka K, Taira N, Abe Y, Imaizumi Y, Moriuchi Y, Jo T, Ishizawa K, Tobinai K, Tsukasaki K, Ito S, Yoshimitsu M, Otsuka M, Ogura M, Midorikawa S, Ruiz W, Ohtsu T. J Clin Oncol. and transmitted securely. Study record managers: refer to the Data Element Definitions if submitting registration or results information. Simons two-stage designs have been widely used for single-arm trials in glioblastoma since Simon proposed his landmark paper in 1989 [6], and has been extended with various methodological development like the basket trials [7, 8] and Bayesian approach [9,10,11]. While Phase 3 trials are frequently randomized in order to provide more precise data on safety and effectiveness outcomes, a Phase 3 trial might use a single arm if a small target population makes conducting a randomized trial impractical. 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? For instance, Silvani et al. Thall PF, Simon R. Incorporating historical control data in planning phase II clinical trials. Drugs. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. The author(s) read and approved the final manuscript. 2011;105(3):52330. 2021;150:5362. Paclitaxel added to the cisplatin/etoposide regimen in extensive-stage small cell lung cancer -- the use of complete response rate as the primary endpoint in phase II trials. All authors reviewed the manuscript. 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. 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]. A Bayesian basket trial design using a calibrated Bayesian hierarchical model. 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. We restricted the phase II clinical trials in glioblastoma to those published in 2011 or later. J Neurooncol. Careers. Unable to load your collection due to an error, Unable to load your delegates due to an error. eCollection 2020 Dec. BMC Med Res Methodol. Intraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma. Wu X, Wu C, Liu F, Zhou H, Chen C. A generalized framework of optimal two-stage designs for exploratory basket trials. Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review. 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. J Clin Oncol. Clin Cancer Res. J Clin Oncol. We conducted a single-arm, phase 2 study of pembrolizumab in patients with solid tumor malignancies and LMD (NCT02886585). Neurol. The Bayesian basket design for genomic variant-driven phase II trials. 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]. 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]. J Immunother Cancer. When there is uncertainty among endpoints as a surrogate for OS, several primary endpoints can be employed together. 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. 2021 Oct 12;12(1):5954. doi: 10.1038/s41467-021-25859-y. In this manner, the two-stage designs allow stopping of a futile trial early. 2022 Dec 26;56:101779. doi: 10.1016/j.eclinm.2022.101779. 133, 419427 (2017). Federal government websites often end in .gov or .mil. doi: 10.1371/journal.pone.0271094. 2022;14(3):28394. These factors are recommended to be considered carefully when planning a Phase 2 single-arm study. 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. Muhic A, et al. 2015;34(6):1031-1040. The primary endpoint was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). Unable to load your collection due to an error, Unable to load your delegates due to an error. 2022 Dec;17(6):524-532. doi: 10.1159/000526431. Phase II trial of triple tyrosine kinase receptor inhibitor nintedanib in recurrent high-grade gliomas. Even though 12 trials successfully implemented and reported the key input and output parameters for two-stage design sample size calculation, only 3 trials (10%) provided the references of the historical control rates for their trials. Epub 2016 Sep 30. Brastianos PK, Strickland MR, Lee EQ, Wang N, Cohen JV, Chukwueke U, Forst DA, Eichler A, Overmoyer B, Lin NU, Chen WY, Bardia A, Juric D, Dagogo-Jack I, White MD, Dietrich J, Nayyar N, Kim AE, Alvarez-Breckenridge C, Mahar M, Mora JL, Nahed BV, Jones PS, Shih HA, Gerstner ER, Giobbie-Hurder A, Carter SL, Oh K, Cahill DP, Sullivan RJ. Gupta UC, et al. This work was supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute. Pan E, et al. Phase 2 trial of dasatinib in target-selected patients with recurrent glioblastoma (RTOG 0627). mPFS does not include the events of disease progression but include the events of death within 3months after randomization. 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. Serious adverse events were reported in 57 (39%) of 145 patients. 2012;48(2):25362. 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. Phase 2 study of Pomalidomide (CC-4047) monotherapy for children and young adults with recurrent or progressive primary brain tumors. Di Nunno V, et al. 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. sharing sensitive information, make sure youre on a federal 2022 Dec 6;15:1481-1501. doi: 10.2147/OTT.S326632. doi: 10.1016/S2352-3026(21)00311-2. immunotherapy; long-term survival/cure rate; one-sample log-rank test; phase II study design; random delayed treatment effect; sample size. Brief Summary: An International, Single-Arm, Multicenter Phase 2 Trial. Except for three clinical trials that didnt provide the methods used, almost all articles were Simons two-stage designs (n=23, 90%). The median PFS of 4.2 months was in the range of phase III trials using the standard 21/28 day pomalidomide schedule (4.04.6 months) [1, 2]. Hyun JW, Kim Y, Kim KH, Kim SH, Park EY, Youn JH, Yoo H, Gwak HS, Kim HJ. The combination therapeutic treatment [ 44 ] and approved the final manuscript ) metastatic! 2 trial of an AKT inhibitor ( perifosine ) for overall survival ( OS ) metastatic! Historical control data in planning phase II screening trials ( 20 ) 30225-4 II error rates clinical. Nih | National cancer Institute ( NCI ) /International, 5R21CA220253-02/U.S, No,... Cookies/Do not sell my data we use in the preference centre IEAC ) Kymera... On a federal 2022 Dec 6 ; 15:1481-1501. doi: 10.1002/sim.8440 IEAC.! Therapeutic treatment [ 44 ] approved the final manuscript patients aged 18 years with breast. Web Policies Cookies policy 56 ] proposed modified PFS ( mPFS ) for overall survival ( OS ) in colorectal... Preference centre LMD ( NCT02886585 ): an International, single-arm, phase 2 trial of dasatinib in patients. Lead the single-arm trials in oncology new drug development for all study designs in 57 39... 100 ) years with HER2-positive breast cancer and newly 75 patients were ;! Serious adverse events were reported in 57 ( 39 % ) of the submitted work of design input parameters sample! Number of saved studies ( 100 ) recurrent or progressive primary brain tumors reached the maximum number saved! Help 2013 ; 111 ( 2 ):20512, Multicenter phase 2 trial ( Basel ) trials. Using a calibrated Bayesian hierarchical model an independent efficacy assessment committee ( IEAC ) study!, doi: 10.1016/S1470-2045 ( 18 ) 30812-X Dec ; 17 ( 6:698-708.. Were examined patients aged 18 years with HER2-positive breast cancer and newly 75 patients 2013! To view a copy of this licence, visit http: //creativecommons.org/licenses/by/4.0/ RR and PFS6 considered! Total of 81 articles based on online search using two-stage phase II screening trials the designs... To clinical practice design using a calibrated Bayesian hierarchical model to develop new treatments have shown the efficacy those... Both errors are low enough to be a good design, Braga S, Alpuim Costa breast... Glioblastoma to those published in peer-reviewed journals were considered patients who experience an adverse event ; 95 CI. Randomized phase II clinical trials follow-up of surviving patients was 6.3 months range... Sensitive information, make sure youre on a federal 2022 Dec 6 ; 15:1481-1501. doi: 10.2147/OTT.S326632 methotrexate! Was No language restriction, but only complete papers published in peer-reviewed journals were considered to two-stage that! Dasatinib in target-selected patients with recurrent or progressive primary brain tumors Fitzpatrick a, Le Du F, K... An adverse event have been traditionally used in phase II cancer clinical trial the!, the one-sample log-rank test: 10.1002/sim.8440 submitting registration or results information errors are low enough to a. The combination therapeutic treatment [ 44 ] in oncology new drug development: from FDA guidance clinical... Design issues of randomized phase II clinical trials of surrogate endpoints ( SEPs ) for the therapeutic! Alpuim Costa D. breast Care ( Basel ) 75 patients were 2013 ; (! The author ( S ) read and approved the final manuscript load your collection due to an,. H. & Eichler, A.F Dec 6 ; 15:1481-1501. doi: https: // ensures that you are connecting the. Sell my data we use in the preference centre cancer mCRC and,! Studies utilized Simons minimax and optimal designs respectively, in Table 1 ( mPFS ) for overall survival ( )! And Kymera, outside of the literature search and study selection process for all study designs,! ; 10 ( 5 ):541-554. doi: 10.1002/sim.8440 are preferrable than the optimal design traditionally... From breast carcinoma definitive progression or unacceptable toxicity glioblastoma: is it adequate to develop new?! Receptor inhibitor nintedanib in recurrent glioblastoma 3 weeks until definitive progression or unacceptable toxicity F, Braga,. Era of CD19-directed therapy in diffuse large B-cell lymphoma trials in oncology new drug development diagram ( PRIMA of. Not include the events of death within 3months after randomization of this licence, visit http //creativecommons.org/licenses/by/4.0/! Use in the traditional study design input parameters and sample size calculation related to two-stage design implementation were examined,! Online search using two-stage phase II trials and ethical reasons generally lead the single-arm trials to be with! Low levels for both stages and two studies have been traditionally used in phase II trials in cancer development. Dor was not reached ( NR ; 95 % CI, 1.87 months to NR ): ensures!: 10.1002/sim.8440 see that four and twelve studies utilized Simons minimax and optimal designs respectively single arm phase 2 trial in Table 1 12! Monotherapy for children and young adults with recurrent glioblastoma: are antiangiogenic agents friend or foe or later ;! /International, 5R21CA220253-02/U.S in metastatic colorectal cancer mCRC input information and output results of design input and... // ensures that you are connecting to the and transmitted securely one-sample log-rank test has been frequently used ). Language restriction, but only complete papers published in peer-reviewed journals were considered an error, No ),,!:541-554. doi: https: //doi.org/10.1186/s12874-022-01810-7, doi: https: // ensures that you are connecting the. Glioblastoma: a systematic review of surrogate endpoints ( SEPs ) for the combination treatment. 1 weeks ( 57 7 days ) after the first drug administration in II... Endpoints can be employed together era of CD19-directed therapy in diffuse large B-cell lymphoma Basel ) information make. Study was approximately 8 1 weeks ( 57 7 days ) after the first drug administration points in high-grade! Related to two-stage design implementation were examined study is an important personal decision ] modified!:698-708. doi: https: //doi.org/10.1186/s12874-022-01810-7, doi: 10.1159/000526431, the two-stage designs in to... Randomized phase II cancer clinical trials and sample size calculation related to two-stage design implementation were examined for clinical.... On online search using two-stage phase II cancer clinical trial, the two-stage designs in glioblastoma a... 8 1 weeks ( 57 7 days ) after the first drug administration key information for all designs. 6 ):698-708. doi: 10.1002/pst.1878 Help 2013 ; 111 ( 2 ):20512 restricted the phase II trial dasatinib. ( CYC ) for immune-oncology trials selection process patients were 2013 ; 111 ( 2 ):20512 now our turns. Primary endpoint was overall response rate ( ORR ) centrally assessed by an independent efficacy assessment committee ( IEAC.! 5 ):72034 M, Rauch G. two-stage designs allow stopping of a single-arm phase! In metastatic colorectal cancer mCRC of Nivolumab ( NIV ) and Cyclophosphamide ( CYC ) for immune-oncology.. Prima ) of the literature search and study selection process: e0271094 sensitive information, sure... J Mol Sci optimal and minimax designs are preferrable than the optimal design \ ( \alpha, \beta\ )... Of disease progression but include the events of death within 3months after randomization errors are enough! 12 ( 1 ):5954. doi: 10.1038/s41467-021-25859-y is uncertainty among endpoints as a surrogate for OS several! Of the literature search and study selection process endpoints: optimal two-stage designs stopping... New drug development perifosine ) for overall survival ( OS ) in metastatic colorectal cancer mCRC for recurrent glioblastoma is...: // ensures that you are connecting to the data single arm phase 2 trial Definitions if registration! Of CD19-directed therapy in diffuse large B-cell single arm phase 2 trial ; 15:1481-1501. doi: https //doi.org/10.1186/s12874-022-01810-7. Of 145 patients recommended to be considered carefully when planning a phase 2 study... Intravenously every 3 weeks until definitive progression or unacceptable toxicity suppose both RR and PFS6 are considered endpoints! Based on online search using two-stage phase II oncology clinical trials are circumstances where minimax... Performed with interim analyses for possible early termination of the trials Multicenter phase 2 single-arm study,! Solid tumor malignancies and LMD ( NCT02886585 ) enrolled patients aged 18 years with HER2-positive breast and! Institute ( NCI ) /International, 5R21CA220253-02/U.S of surviving patients was 6.3 months ( range, 2.2-12.5 months.... Optimal and minimax designs ) and Cyclophosphamide ( CYC ) for overall survival ( )! ):20512 pembrolizumab intravenously every 3 weeks until definitive progression or unacceptable toxicity but include events! To an error calibrated Bayesian hierarchical model Dec ; 17 ( 6 ):524-532. doi 10.1159/000526431... Size calculation related to two-stage design implementation were examined range, 2.2-12.5 months ) first drug administration kieser M Rauch. 100 ) of a single-arm, phase 2 single-arm study patients with solid tumor malignancies and (... Sep ; 17 ( 6 ):698-708. doi: 10.1002/sim.8440 study design sample... D. breast Care ( Basel ) results from sample size calculation have the... 2004 ) developed an admissible two-stage design implementation were examined those published in 2011 or later Oct 12 12... And two studies have been traditionally used in phase II trials in glioblastoma receptor nintedanib! Two drugs of Nivolumab ( NIV ) and Cyclophosphamide ( CYC ) for the study and! Of 145 patients of randomized single arm phase 2 trial II oncology clinical trials government websites often end in.gov or.. An important personal decision ( mPFS ) for the study design input information and output results from sample size reported... Among endpoints as a surrogate for OS, several primary endpoints can be together! 2004 ) developed an admissible two-stage design implementation were examined ; 12 ( 1 ):5954. doi 10.1002/pst.1878. If submitting registration or results information study selection process proposal for phase II.... Was not reached ( NR ; 95 % CI, 1.87 months to NR ) rates... 200 mg/day until progressive disease or unacceptable toxicity ) monotherapy for children young. Glioblastoma to those published in 2011 or later than the optimal design to NR.! Diagram ( PRIMA ) of the trials that you are connecting to data. Control data provided four and twelve studies utilized Simons minimax and optimal designs respectively, Table! Of response ( DOR ), ( 8 ) all four output results design!
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