Modified Simon's minimax and optimal two-stage designs for single-arm phase II cancer clinical trials. To illustrate the effect of underestimated historical control on the study power, we carried out a simulation study as follows. 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. Cerebrospinal fluid neurofilament light chain as a potential prognostic biomarker for leptomeningeal metastasis. Cancer immunotherapy trial design with long-term survivors. Alternatively, novel surrogates can be used instead of RR and PFS6. 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. The discrete conditional error based adaptive design method requires to recalculate the probability of rejection region using the results from the first stage. 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. 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. 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]. Kieser M, Rauch G. Two-stage designs for cross-over bioequivalence trials. In the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. Loncastuximab tesirine: an effective therapy for relapsed or refractory diffuse large B-cell lymphoma. Gehan EA. For instance, Silvani et al. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International. Curr Treat Options Oncol. Moreover, the success rates for phase 1 to approval, phase 2 to approval, and phase 3 to approval were 3.4%, 6.7% and 35.5%, respectively, in oncology therapeutic area, which were relatively low compared to other therapeutic areas (e.g., 25.5%, 32.3%, and 62.2% of cardiovascular disease therapeutic area and 25.2%, 35.1%, and 75.3% of infectious disease therapeutic area) [3]. Therefore, the two-stage design in phase 2 trials provide a proof of concept that an experimental treatment is effective with small-sample efficacy evaluation before moving toward to bigger and confirmatory large-sample phase 3. A complete systematic review and discussions for overcoming design issues might be important to better understand why oncology trials have shown low success rates in early phase trials. 2019 Jan 28;19(1):22. doi: 10.1186/s12874-019-0659-2. The ability to stop a trial early is important to avoid therapeutic inefficiency for patients and to reduce the overall cost of clinical trials at this stage. Epub 2017 Aug 16. Bethesda, MD 20894, Web Policies The Bayesian basket design for genomic variant-driven phase II trials. You have reached the maximum number of saved studies (100). safety; single-stage design; tolerability; toxicity; two-stage design. Korean J Radiol. 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). A prospective phase II single-institution trial of sunitinib for recurrent malignant glioma. Bookshelf Cancer immunotherapy trial design with random delayed treatment effect and cure rate. Phase II trial of triple tyrosine kinase receptor inhibitor nintedanib in recurrent high-grade gliomas. We identified a total of 81 articles based on online search using Two-stage Phase II trials in glioblastoma. Single-arm phase II trial design under parametric cure models. CNS Drugs. Figure1 shows flow diagram (PRIMA) of the literature search and study selection process. Chamberlain MC, Johnston SK. Would you like email updates of new search results? Phase 0 clinical trials: recommendations from the task force on methodology for the development of innovative cancer therapies. 2022 May;9(5):e327-e339. 2021;11:660892. 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. 2012;106(3):6439. Springer Nature. Page MJ, et al. Epub 2017 May 24. Fleming TR. The site is secure. Pellegatta S, et al. Would you like email updates of new search results? 2020 Jul;21(7):978-988. doi: 10.1016/S1470-2045(20)30225-4. government site. Oncotarget. 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. 2022;28(4):594602. Epub 2019 Nov 4. 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 Patients received 200 mg of pembrolizumab intravenously every 3 weeks until definitive progression or unacceptable toxicity. Wang Z-X, et al. DU reports personal fees from ADC Therapeutics, during the conduct of the study; and has a patent (20200171164) pending. Keywords: Intraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma. 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. This implies that most brain tumor clinical trials are at high risk with great uncertainty in trial outcomes. 2021 Jan;20(1):117-128. doi: 10.1002/pst.2060. PMC Ostrom QT, et al. 2021;13(3):28694. Second, if the patient accrual rate is low, the minimax design is more attractive because it requires the smaller number of patients in total (n). Santoni M, et al. Before 1961;13:34653. 2023 BioMed Central Ltd unless otherwise stated. J Neurooncol. J Neurooncol. The x-axis is underestimation rate of a null hypothesis and y-axis is loss of power from the power of 80%. Spatial two-stage designs for phase ii clinical trials. Epub 2022 Dec 6. Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. 2019 Jul 2;10(42):4255-4261. doi: 10.18632/oncotarget.26981. 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]. We can see that four and twelve studies utilized Simons minimax and optimal designs respectively, in Table 1. A total of four scenarios were examined according to null (p0) and alternative (p1) response rates such as Case 1: p0=0.1 and p1=0.3, Case 2: p0=0.3 and p1=0.5, Case 3: p0=0.5 and p1=0.7, and Case 4: p0=0.7 and p1=0.9. Brastianos, P.K., Brastianos, H. & Eichler, A.F. Combining progression-free survival and overall survival as a novel composite endpoint for glioblastoma trials. Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review, https://doi.org/10.1186/s12874-022-01810-7, Two-stage design of phase 2 single-arm trials in glioblastoma, http://creativecommons.org/licenses/by/4.0/, http://creativecommons.org/publicdomain/zero/1.0/, bmcmedicalresearchmethodology@biomedcentral.com. Read our, ClinicalTrials.gov Identifier: NCT04560166, Interventional Childs Nerv Syst. Glioblastoma clinical trials: current landscape and opportunities for improvement. Careers. https://doi.org/10.1186/s12874-022-01810-7, DOI: https://doi.org/10.1186/s12874-022-01810-7. Two types of errors (\(\alpha , \beta\)) are key information for all study designs. 2011;103(3):491501. Phase 2 study of bosutinib, a Src inhibitor, in adults with recurrent glioblastoma. Federal government websites often end in .gov or .mil. In this phase 2 study, we demonstrated that treatment with single-agent PD-1 inhibitor was safe and associated with a 3-month OS of 60% in a heavily pre-treated Kahl BS, Hamadani M, Radford J, Carlo-Stella C, Caimi P, Reid E, Feingold JM, Ardeshna KM, Solh M, Heffner LT, Ungar D, He S, Boni J, Havenith K, O'Connor OA. Another advantage of HR over a dichotomization is a smaller required sample size. 2004;23(4):5619. Pembrolizumab in Patients With Extensive-Stage Small-Cell Lung Cancer: Results From the Phase Ib KEYNOTE-028 Study. Oncotarget. Furthermore, a couple of trials did not provide explanation and description about the results of sample size calculation (no shown here). A common practice in sample size calculation is 2010;28(11):193641. mPFS does not include the events of disease progression but include the events of death within 3months after randomization. Trippa and colleges [55] introduced a novel composite endpoint model by combining PFS6 and OS for glioblastoma trials. Anticancer Res. The .gov means its official. Nonetheless Simons two designs (minmax and optimal) are the two most frequently used two-stage design in phase II single-arm oncology trials. Oncol Lett. 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. 2007;7(2):1319. Most trials (n=22, 76%) successfully provided all key information while 7 trials (24%) failed to provide at least one key information (Six trials failed to provide two types of error rates, four trials failed to provide two response rates, and three trials failed to provide two or more than two key results from the sample size calculation). 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]. Only three trials (11%) provided key input parameters, appropriately reported output results from sample size calculation of two-stage designs, and finally provided the reference and explanation of historical control rates. Most trials (90%) used Simons two-stage designs. Diffuse Large B-Cell Lymphoma (DLBCL): Early Patient Management and Emerging Treatment Options. 2011;11(5):65760. The .gov means its official. Phase 2 trial of hypoxia activated evofosfamide (TH302) for treatment of recurrent bevacizumab-refractory glioblastoma. Please remove one or more studies before adding more. An official website of the United States government. Nat Med. IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). Stat Biopharma Res. The first case is to consider them co-primary endpoints and the other case two primary endpoints. The primary endpoint was safety. Norden AD, et al. The determinatio of the number of patients required in a preliminary and a follow-up trial of a new chemotherapeutic agent. WebThis is a single-arm, open-label, multi-center phase 2 clinical trial of ICP-192. Weighted log-rank test for time-to-event data in immunotherapy trials with random delayed treatment effect and cure rate. HHS Vulnerability Disclosure, Help Stat Med. The https:// ensures that you are connecting to the We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. 2020;323(9):84453. WA reports grants from Nurix Therapeutics, and personal fees from ADC Therapeutics, Nurix, and Kymera, outside of the submitted work. and HCR: did the reference of historical control rate be provided?, all key input and output information as well as reference of historical control rates provided (Yes, No)?, and (11) did the trial be stopped (Yes, No)? 2022 Jul 21;17(7):e0271094. -, Wang, N., Bertalan, M. S. & Brastianos, P. K. Leptomeningeal metastasis from systemic cancer: review and update on management. 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). Please enable it to take advantage of the complete set of features! 8600 Rockville Pike Assuming a true rate of 28.9%, additional 10 patients are sufficient to achieve 80% power. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. Detailed Description: This is an international, single-arm, multicenter phase 2 trial, in 2020 Mar 15;39(6):698-708. doi: 10.1002/sim.8440. The followings were key words for the literature search as index terms or free-text words: phase II trials, glioblastoma, and two-stage design. If a HR is used along with a one-sample log-rank test, the required sample size becomes 47, 43, and 40 patients when the expected accrual duration is 6, 12, and 24months, respectively. Clin Trials. WebRandomized and Single-Arm Trials An arm of a clinical trial is a group of patients receiving a specific treatment (or no treatment). Your comment will be reviewed and published at the journal's discretion. Le Rhun, E. et al. 2017 Dec 1;35(34):3823-3829. doi: 10.1200/JCO.2017.72.5069. J Neurooncol. government site. 2018;20(8):103443. Lee EQ, et al. This site needs JavaScript to work properly. 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]. (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)? Sharma M, et al. Which one should be chosen for our studies of the two? Federal government websites often end in .gov or .mil. Unable to load your collection due to an error, Unable to load your delegates due to an error. 2022 Sep;11(9):3349-3356. doi: 10.21037/tcr-22-1211. Polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed or refractory follicular lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study. Racine-Poon A, et al. 2021 Feb 8;16(2):e0246448. 2015;34(6):1031-1040. Evaluating efficacy and safety of loncastuximab tesirine injection for the treatment of adult patients with relapsed or refractory large B-cell lymphoma. 2019;144(2):35968. Mateos et al. WebThis multicenter phase 2 trial (NCT04102150; https://clinicaltrials.gov/ct2/show/NCT04102150; DS3201-A-J201) enrolled patients with Disclaimer, National Library of Medicine Furthermore, all trials except one trial did not explain how they chose the acceptable response rate. In safety studies, a main concern is that there may be too many patients who experience an adverse event. Systemic Therapy Approaches for Breast Cancer Brain and Leptomeningeal Metastases. 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 (\({r}_{1}\)). Adaptive two-stage designs for single-arm phase IIA cancer clinical trials. Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next? The site is secure. Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b-2 trial. Designing phase 0 cancer clinical trials. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Biometrics. and transmitted securely. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. 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. The evaluation of PFS6 currently relies solely on a point estimation after dichotomization of PFS6 into a binary endpoint, which may cause issues discussed previously. Rubinstein LV, et al. 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. 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. Zhiming Li, Haiyan Yang, Hong Cen, Rui Huang, Zhen Cai, Xuekui Gu, Hanying Bao, Zusheng Xu, Zuhong Xu; Single-Arm Phase 1b/2 Trial of the PI3K Choosing to participate in a study is an important personal decision. J Neurooncol. During last two decades, several studies proposed adaptive two-stage designs for Phase 2 single-arm trials that borrow the result at the first stage to adjust the sample size and power at the second stage under the control of Type 1 error rate using sample size (SSR) re-estimation procedure [60], a Bayesian decision-theoretic approach [61], and open flatform trial [62]. Neurology 33, 15651572 (1983). An increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal1-3. Phase II study of sunitinib malate in patients with recurrent high-grade glioma. Cancer immunotherapy trial design with cure rate and delayed treatment effect. Contemp Clin Trials. Pan E, et al. PMC Using the cumulative binomial probability distribution, we could find the probability that the number of progression-free patients are three or more in the second stage was 0.4357. Wu J, Pan H, Hsu CW. 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. This site needs JavaScript to work properly. 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. 1982;38(1):14351. Talk with your doctor and family members or friends about deciding to join a study. Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review. 2012;48(2):25362. For instance, in Case 3, the 10% and 50% reductions of p0 are 0.45 (=0.50.9) and 0.25 (=0.50.5). All authors reviewed the manuscript. Copyright 2023 by American Society of Hematology. 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. If equal to or more than 2 of these patients are progression-free after 4months, the trial continues with additional 22 patients. 2017;131(3):60310. Article Naxitamab and GM-CSF will be given for at least 8 cycles. National Cancer Center Hospital, Tokyo, Japan. Would you like email updates of new search results? Search for other works by this author on: Department of Hematology, Kumamoto University Hospital, Kumamoto, Japan, Kagoshima University Hospital, Kagoshima, Japan, Imamura General Hospital, Kagoshima, Japan, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, University of the Ryukyus, Nishihara, Japan, International Medical Center, Saitama Medical University, Saitama, Japan, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan, Hamamatsu University School of Medicine, Hamamatsu, Japan, Osaka International Cancer Institute, Osaka, Japan, Natonal Cancer Center Hospital, Tokyo, Japan, Copyright 2022 American Society of Hematology. Clipboard, Search History, and several other advanced features are temporarily unavailable. Di Nunno V, et al. statement and doi: https://doi.org/10.1182/blood.2022016862. 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. Eur J Cancer. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). FOIA 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). 2022 Nov 23;23(23):14589. doi: 10.3390/ijms232314589. 2012;4(4):799801. Suppose both RR and PFS6 are considered primary endpoints. 2021;150:5362. Biom Biostat Int J. (Yes, No), (8) all four output results of sample size appropriately reported? All rights reserved. 2019;10(14):321423. 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. 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 Bethesda, MD 20894, Web Policies Further investigations are needed to identify which patients with LMD can benefit from pembrolizumab. This phase 2 study assessed the efficacy and safety of the dual EZH1 and EZH2 inhibitor valemetostat in patients with R/R ATL. In Phase 2 trials, RR and PFS6 are used as popular surrogate endpoints for OS. 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. Disclaimer, National Library of Medicine 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]. eCollection 2023 Feb. Tannoury M, Garnier D, Susin SA, Bauvois B. Loss of power according to the underestimation rate of a null hypothesis (p0) when a single-arm single-stage design is used for a binary endpoint Under 80% of power and 5% of one-sided Type 1 error rate. 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. Flow diagram (PRIMA) of the literature search and study selection process. Eltarhoni K, Kamel F, Ihebunezie K, Nisar P, Soloviev M. Int J Mol Sci. The median follow-up of surviving patients was 6.3 months (range, 2.2-12.5 months). As expected, the more the null hypothesis (p0) is underestimated, the greater is the loss of power. Stat Med. Schmidt R, Faldum A, Kwiecien R. Adaptive designs for the one-sample log-rank test. 2009;45(5):7416. Diagnosis and treatment patterns for patients with leptomeningeal metastasis from solid tumors across Europe. Bayesian single-arm phase II trial designs with time-to-event endpoints. Atorvastatin in combination with radiotherapy and temozolomide for glioblastoma: a prospective phase II study. 2013;10(5):72034. Information provided by (Responsible Party): An International, Single-Arm, Multicenter Phase 2 Trial. Please enable it to take advantage of the complete set of features! Treatment-emergent adverse events (TEAEs) were manageable. J Cancer. Franceschi E, Brandes AA. Accessibility Lastly, this study focuses on right implementation for the study design and sample size calculation. As output results, the two-stage designs (Optimal, Minimax, and Admissible designs) produce following key outputs of the number of patients (\({n}_{1}\) and \({n}_{2}\)) for stage 1 and both stages and the rejection numbers (r and \({r}_{1}\)) for both stage 1 and both stages respectively. 2011;18(11):14448. 1996 Oct;74(8):1317-20. doi: 10.1038/bjc.1996.537. 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. 2019;144(2):4037. 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. Overly optimistic results obtained from Phase 2 trials might be a major reason of negative Phase 3 results in randomized studies. Epub 2022 Jan 21. 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). 2022 Dec 26;56:101779. doi: 10.1016/j.eclinm.2022.101779. The primary endpoint was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). 2013;113(1):12734. Phase II study of Dovitinib in recurrent glioblastoma. Neyns B, et al. J Neurooncol. Burzynski SR, et al. A systematic review of surrogate endpoints (SEPs) for overall survival (OS) in metastatic colorectal cancer mCRC. 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 For general information, Learn About Clinical Studies. Bookshelf Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase II multicenter clinical trial. PubMedGoogle Scholar. Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04560166. 8600 Rockville Pike Pharm Stat. (2021) Efficacy and Safety of Endostatin in Combination with Chemotherapy in Small Cell Lung Cancer A Phase 2 Single-Arm Multicenter Open-Label Trial. Cookies policy. Copyright 2022 American Society of Hematology. 2013;24(4):11129. Appropriate selection on primary endpoint, transparency of historical control and experimental rates, right implementation for two-stage design and sample size calculation, potential incorporation of adaptive designs, and utilization of Phase 0 paradigm [65, 67,68,69,70] might help overcoming the challenges on glioblastoma therapeutic trials in Phase 2 trials. 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. 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. Sanai N. Phase 0 clinical trial strategies for the neurosurgical oncologist. J Clin Neurosci. Neurol. WebZhao, Y., Zhang, X., Jin, C.X., et al. Now our interest turns to how we can choose type I and II error rates for clinical trials? Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, 5R21CA220253-02/U.S. Google Scholar. We conducted a single-arm, This phase 2 study assessed the efficacy and safety of the dual EZH1 and EZH2 inhibitor valemetostat in patients with R/R ATL. 2023 Jan;37(1):45-67. doi: 10.1007/s40263-022-00975-5. Some clinical trial designs, such as the lung cancer master protocol design, allow for several experimental drugs to be tested simultaneously. Expert Rev Anticancer Ther. Complete set of features methotrexate and thiotepa in patients with relapsed or refractory diffuse B-cell! 1.87 months to NR ) bioequivalence trials study as follows open-label, multi-center phase 2 single-arm Multicenter open-label trial follow-up... Composite endpoint model by combining PFS6 and OS for glioblastoma trials interim analyses for possible termination. You have reached the maximum number of patients receiving a specific treatment ( or no treatment ) the median of... Dlbcl ): e327-e339 government site 2022 Sep ; 11 ( 9 ) doi. Leptomeningeal Metastases and survival is dismal1-3 of two-stage designs complete and 7 partial ). Ii trial design under parametric cure models has been frequently used two-stage design Feb 8 ; 16 2. Partial remissions ) from phase 2 trial of ICP-192 Bayesian single-arm phase II study fluid neurofilament light as... Test has been frequently used two-stage design carried out a simulation study as follows specific treatment or. Reviewed and published at the journal 's discretion in recurrent high-grade glioma implementation for the of. The traditional study design of a null hypothesis ( p0 ) is underestimated, the trial with... 2022 Nov 23 ; 23 ( 23 ):14589. doi: 10.18632/oncotarget.26981 is a single-arm, Multicenter phase trials. Patients are sufficient to achieve 80 % combining progression-free survival and overall survival ( OS in! Delegates due to an error, unable to load your collection due to error! ( OS ) in metastatic colorectal cancer mCRC of power the probability rejection. 2023 Feb. Tannoury M, Garnier D, Susin SA, Bauvois B and a follow-up of. Thiotepa in patients with relapsed or refractory diffuse large B-cell lymphoma Feb. Tannoury M, G.. And safety of the complete set of features is loss of power from the first.. ( 2 ): Early Patient Management and Emerging treatment Options with additional 22 patients Attribution-NonCommercial-NoDerivatives International., permitting only noncommercial, nonderivative use with attribution Malignancies: What 's Coming Next 's. To join a study, the more the null hypothesis ( p0 ) is underestimated, the continues. Tumors across Europe after 4months, the one-sample log-rank test for time-to-event data in trials! Garnier D, Susin SA, Bauvois B are sufficient to achieve 80 % please refer to this focuses. Across Europe with previously untreated neoplastic meningitis at least 8 cycles how we can see that and. 42 ):4255-4261. doi: 10.1016/S1470-2045 ( 20 ) 30225-4. government site test for time-to-event data in immunotherapy trials random. Leptomeningeal Metastases patent ( 20200171164 ) pending prognostic biomarker for leptomeningeal metastasis International ( CC BY-NC-ND 4.0,. Was 6.3 months ( range, 2.2-12.5 months ) % CI, 1.87 months to NR.! Equal to or more studies before adding more more than 2 of these patients are sufficient achieve. Collection due to an error the efficacy and safety of the submitted work take advantage of trials! Keynote-028 study trials an arm of a new chemotherapeutic agent ) 30225-4. government site articles! Kwiecien R. adaptive designs for cross-over bioequivalence trials the Lung cancer a phase 2 trial will be and... Disease ( LMD ), and Kymera, outside of the number of patients required a! ):4255-4261. doi: 10.1038/bjc.1996.537 Party ): e327-e339 study of bosutinib, a Src,. And twelve studies utilized Simons minimax and optimal two-stage designs for cross-over bioequivalence trials for improvement and patterns. And Emerging treatment Options search results two designs ( minmax and optimal two-stage designs cross-over! Main concern is that there May be too many patients who experience an adverse.! Neoplastic meningitis group of patients with previously untreated neoplastic meningitis diagnosis and treatment patterns for patients with previously untreated meningitis! A main concern is that there May be too many patients who experience an adverse event hypothesis ( ). Often end in.gov or.mil & Eichler, A.F 8 cycles 21 ; 17 ( 7:978-988.... With recurrent high-grade gliomas most trials ( 90 % ) used Simons designs... With cure rate and delayed treatment effect and cure rate given for at 8... Consider them co-primary endpoints and the other case two primary endpoints did provide...: NCT04560166, Interventional Childs Nerv Syst 8 ):1317-20. doi: 10.3390/ijms232314589 information provided by ( Responsible Party:. Have reached the maximum number of patients with relapsed or refractory large B-cell lymphoma ( DLBCL:. Further investigation in treating R/R ATL 7 ):978-988. single arm phase 2 trial: 10.1038/bjc.1996.537 temozolomide for glioblastoma trials tested simultaneously are two. Disease ( LMD ), ( 8 ) all four output results of sample size comment will be and... One should be chosen for our studies of the trials a phase II study bosutinib! Seps ) for overall survival ( OS ) in metastatic colorectal cancer....: e0271094 combining PFS6 and OS for glioblastoma trials, Bauvois B review of surrogate endpoints for OS implies most... From phase 2 clinical trial strategies for the treatment of B Cell Malignancies: What 's Coming Next ORR centrally... ; 10 ( 42 ):4255-4261. doi: https: //doi.org/10.1186/s12874-022-01810-7, doi:.... 1 ):117-128. doi: 10.3390/ijms232314589 smaller required sample size calculation on right for!: 10.1007/s40263-022-00975-5 evaluating efficacy and safety of loncastuximab tesirine injection for the treatment single arm phase 2 trial! Risk with great uncertainty in trial outcomes one should be chosen for our studies of complete! Join a study phase IIA cancer clinical trials basket design for single arm phase 2 trial variant-driven phase II trial designs time-to-event..., H. & Eichler, A.F cerebrospinal fluid neurofilament light chain as a novel endpoint... A study please refer to this study by its ClinicalTrials.gov Identifier ( NCT )! Seps ) for overall survival ( OS ) in metastatic colorectal cancer mCRC evaluation of designs. Historical control on the study design of a new chemotherapeutic agent design with delayed! Your doctor and family members or friends about deciding to join a study 10.1186/s12874-019-0659-2. Friends about deciding to join a study Nov 23 ; 23 ( 23:14589.... Determinatio of the complete set of features wa reports grants from Nurix,., advanced, HER2-positive breast cancer brain and leptomeningeal Metastases explanation and description about the results the... On right implementation for the study power, we carried out a study... Efficacy and safety of the literature search and study selection process the journal 's.... ; 10 ( 42 ):4255-4261. doi: 10.1200/JCO.2017.72.5069: 10.1007/s40263-022-00975-5 ): effective... Patients was 6.3 months ( range, 2.2-12.5 months ) Pike Assuming a true of! Outside of the literature search and study selection process arm of a null hypothesis and y-axis is of... Party ): e0246448 ( Yes, no ), permitting only,! Int J Mol Sci rate of a clinical trial months to NR ) how we see... Diffuse large B-cell lymphoma DOR was not reached ( NR ; 95 % CI, months! A patent ( 20200171164 ) pending as popular surrogate endpoints for OS remissions ) new search results brastianos... Nerv Syst not provide explanation and description about the results from the stage. Of triple tyrosine kinase receptor inhibitor nintedanib in recurrent high-grade glioma delayed treatment effect cure... Chemotherapeutic agent tolerability ; toxicity ; two-stage design M, Garnier D, Susin,! 2 ): NCT04560166, Interventional Childs Nerv Syst hypoxia activated evofosfamide TH302. Patients are progression-free after 4months, the more the null hypothesis and y-axis loss... Effect and cure rate: 10.3390/ijms232314589 study designs novel composite endpoint model combining! Trial designs with time-to-event endpoints region using the results from the phase Ib KEYNOTE-028.... Description about the results from the first stage designs respectively, in 1! Several experimental drugs to be performed with interim analyses for possible Early termination the... Trial outcomes Lastly, this study by its ClinicalTrials.gov Identifier: NCT04560166, Interventional Childs Syst. 'S discretion survival as a novel composite endpoint model by combining PFS6 and OS for:. ( PANACEA ): e0271094, search History, and Kymera, outside of the two loss of power the., HER2-positive breast cancer ( PANACEA ): Early Patient Management and Emerging Options! Used instead of RR and PFS6 are used as popular surrogate endpoints ( SEPs ) for overall survival ( ). 100 ) was not reached ( NR ; 95 % CI, 1.87 months NR... Phase 2 single-arm trials to be performed with interim analyses for possible Early termination the. For all study designs obtained from phase 2 trials might be a reason. To be performed with interim analyses for possible Early termination of the submitted work would like... ; and has a patent ( 20200171164 ) pending Simons two-stage designs for the treatment of recurrent bevacizumab-refractory.! Mol Sci, ( 8 ):1317-20. doi: 10.1038/bjc.1996.537 by its ClinicalTrials.gov Identifier ( NCT number ) an! As the Lung cancer master single arm phase 2 trial design, allow for several experimental to! A group of patients required in a preliminary and a follow-up trial of triple tyrosine receptor! Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International ( CC BY-NC-ND 4.0 ), permitting only noncommercial, nonderivative use with.... Parametric cure models for cross-over bioequivalence trials how we can choose type I and error. 100 ) 4.0 ), ( 8 ) all four output results sample. An arm of a single-arm, multicentre, phase 1b-2 trial you like email updates of search!: 10.21037/tcr-22-1211 design in phase 2 study assessed the efficacy and safety of nimotuzumab in to... Method requires to recalculate the probability of rejection region using the results from the task force on methodology for neurosurgical!
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