Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, 1R01CA244975-01/U.S. BMJ. Oncotarget. WebZhao, Y., Zhang, X., Jin, C.X., et al. Stat Med. Anticancer Res. Federal government websites often end in .gov or .mil. Furthermore, all trials except one trial did not explain how they chose the acceptable response rate. J Neurooncol. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International. Cancers (Basel). We also sought to understand how these two-stage trials have been implemented, and discussion of potential design issues which we hope will be helpful for investigators work with Phase 2 clinical trials in rare and high-risk cancer studies including Neuro-Oncology. Epub 2019 Nov 4. 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. Findings: Between March 30, 2015, and Aug 3, 2018, 79 patients were enrolled. Pharm Stat. Re-formulating Gehan's design as a flexible two-stage single-arm trial. Choosing to participate in a study is an important personal decision. MeSH Mateos et al. 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. 2019;142(3):45562. Would you like email updates of new search results? Careers. Phase II study of Dovitinib in recurrent glioblastoma. A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma. Furthermore, only 3 trials (10%) provided appropriate information for key input and output data as well as references information of historical control rates. The two types of errors (\(\alpha , \beta\)) and unacceptable and acceptable response rates (\({p}_{0}, {p}_{1}\)) are key input information for successful sample size calculation of two-stage design. Epub 2019 Feb 11. Cite this article. Biometrics. Kwak M, Jung S-H. Lancet Oncol. This phase 2 study assessed the efficacy and safety of the dual EZH1 and EZH2 inhibitor valemetostat in patients with R/R ATL. Simon's two-stage designs are frequently used in phase II single-arm trials for efficacy studies. 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. 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. Weighted log-rank test for time-to-event data in immunotherapy trials with random delayed treatment effect and cure rate. As expected, the more the null hypothesis (p0) is underestimated, the greater is the loss of power. 2005;23(28):7199206. 2022 Sep;11(9):3349-3356. doi: 10.21037/tcr-22-1211. Among 29 reviewed articles, majority study types were glioblastoma (n=20, 69% over high-grade glioma, n=9, 31%) with recurrent patients (n=23, 79% over newly diagnosed patients, n=6 and 21%) and adult patients (n=22, 76% over pediatric population, n=7, 24%). The choice of type I and type II errors is highly important since researchers need to assure that potentially effective therapy is not abandoned and at the same time the insignificant studies with very small marginal effects should not be advanced to subsequent phase III studies. 1982;38(1):14351. Stat Med. WebThe SAUL study has been published. The era of CD19-directed therapy in diffuse large B-cell lymphoma. FOIA A systematic review of surrogate endpoints (SEPs) for overall survival (OS) in metastatic colorectal cancer mCRC. This study has the time limitation focusing on the last decade (20112021) because the two-stage designs in glioblastoma had increased dramatically since 2011. J Clin Oncol. doi: 10.1371/journal.pone.0271094. doi: 10.1016/S2352-3026(21)00311-2. 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). Curr Treat Options Oncol. 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. The .gov means its official. Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04560166. Wouters OJ, McKee M, Luyten J. 2019;93(19):1799806. An armof a clinical trial is a group of patients receiving a specific treatment (or no treatment). 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. 4). Oncoimmunol. BMC Med Res Methodol 22, 327 (2022). 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. 1R01CA227156-01/U.S. Unable to load your collection due to an error, Unable to load your delegates due to an error. The https:// ensures that you are connecting to the PMC Therefore, it is highly important to provide key information about input and output parameters and detail information on the choice of historical control rates based on the reference and the rational reason on the expected target response rate based on previous studies. (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)? An official website of the United States government. Suh CH, et al. Bookshelf Overly optimistic results obtained from Phase 2 trials might be a major reason of negative Phase 3 results in randomized studies. FOIA Lassman AB, et al. The primary endpoint was safety. 2015;121(3):55763. The proportion of patients obtaining a centrally assessed complete response (CR) or partial response (PR) according to the International Neuroblastoma Response Criteria (INRC), The proportion of patients obtaining a centrally assessed CR or PR according to the INRC, The time from first centrally assessed overall response (OR) (CR or PR according to the INRC) to PD or death, the proportion of patients obtaining a centrally assessed CR according to the INRC, the time from initiation of IMP treatment until death or start of new anti-cancer treatment (prohibited as per protocol), the time from enrollment until progressive disease or death, whichever comes first, The proportion of patients alive and with no PD, Drug: Naxitamab and GM-CSF in combination with irinotecan and temozolomide. And 7 trials were used with (1) 5% and 20% (2) 10% and 10% as their type 1 and 2 errors respectively. The study met the primary endpoint, as 12 of 20 (OS3, 0.60; 90% confidence interval, 0.39-0.78) patients were alive at 3 months after enrollment. J Neurooncol. 2007;7(2):1319. 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, WebA Single-arm, Multicenter, Phase 2 Trial to Evaluate Efficacy and Safety of Lenvatinib in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic TACE-HAIC Plus Lenvatinib for Patients With Unresectable HCC: an Open-label, Single-arm, Phase 2 Trial (Thalen) The safety and scientific validity of this study 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 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. J Neurooncol. 2019;144(2):35968. Bayesian hierarchical modeling of patient subpopulations: efficient designs of Phase II oncology clinical trials. Trials involving several arms, or randomized PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. Copyright 2021 Elsevier Ltd. All rights reserved. 2020 Mar 15;39(6):698-708. doi: 10.1002/sim.8440. Valemetostat 200 mg orally once daily demonstrated promising efficacy and manageable toxicity in heavily pretreated patients. Clipboard, Search History, and several other advanced features are temporarily unavailable. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). Pharm Stat. 3). 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. Schmidt R, Kwiecien R, Faldum A, Berthold F, Hero B, Ligges S. Sample size calculation for the one-sample log-rank test. Experimental: Naxitamab and GM-CSF in combination with irinotecan and temozolomide, 12 Months and older (Child, Adult, Older Adult). 14. 2004;60(2):48290. Friends of Cancer Research is a 501 (C)(3) non-profit organization.Our tax ID number is 52-1983273. ADC Therapeutics. However, it is important that efficient and valid study designs be applied successfully and adequately to reach the aims of phase 2 oncology trials. 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. 2003;95(19):1434-1439. 2023 Jan;37(1):45-67. doi: 10.1007/s40263-022-00975-5. However, we should acknowledge there exist heterogeneities when we borrow the historical control information from other published studies due to different population conditions and quality of supportive care. Please check for further notifications by email. Cancer Med. 2008;14(12):367582. Recent research reported that the success rate in proceeding from Phase 2 to Phase 3 was the lowest among all three rates of Phase 1 to 2, Phase 2 to 3, and Phase 3 to approval (e.g., 29.7%, 20.3%, and 35.5% for oncology and 35.2%, 27.4%, 59% for overall) [2]. All rights reserved. Let us now assume that 4 (36.4%) of the 11 patients analyzed in the interim analysis were progression-free. 2022 Nov 23;23(23):14589. doi: 10.3390/ijms232314589. Single-arm phase II trial design under parametric cure models. Keywords: It might look reasonable to select the historical controls from previous research studies if the study is homogeneous with the previous studies. J Neurooncol. 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. 2022. Le Rhun, E. et al. This multicenter phase 2 trial (NCT04102150; https://clinicaltrials.gov/ct2/show/NCT04102150; DS3201-A-J201) enrolled patients with R/R aggressive ATL (acute, lymphoma, unfavorable chronic type). Phase 2 trial of temozolomide and pegylated liposomal doxorubicin in the treatment of patients with glioblastoma multiforme following concurrent radiotherapy and chemotherapy. Phase II trial of ponatinib in patients with bevacizumab-refractory glioblastoma. 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 Please enable it to take advantage of the complete set of features! 2019;85(6):E96774. 2011;18(11):14448. Funding: Unable to load your collection due to an error, Unable to load your delegates due to an error. The purpose of this study is to evaluate the efficacy and safety in patients with FGFR2-Rearranged unresectable or metastatic intrahepatic cholangiocarcinoma who failed prior therapy Arms and Interventions Arm: Experimental Drug ICP-192 Outcome Measures -, Wang, N., Bertalan, M. S. & Brastianos, P. K. Leptomeningeal metastasis from systemic cancer: review and update on management. 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. HHS Vulnerability Disclosure, Help Patients were required to have ECOG PS2 and disease progression during or following 13 prior treatments. The .gov means its official. 2022 Dec 6;15:1481-1501. doi: 10.2147/OTT.S326632. 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. The Bayesian basket design for genomic variant-driven phase II trials. Stat Med. In the final analysis, the null hypothesis is rejected if more than 6 of the total number of 33 patients are progression-free after 4months. Bookshelf 2017 Jul;18(7):895-903. doi: 10.1016/S1470-2045(17)30380-7. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. sharing sensitive information, make sure youre on a federal Among 29 trials, only three has been completed for both stages and two studies have shown the efficacy. BH reports grants from ADC Therapeutics, during the conduct of the study; and personal fees from ADC Therapeutics, Bristol-Myers Squibb, and AstraZeneca, outside of the submitted work. 8600 Rockville Pike The other three trials used two-stage designs like Inadmissible design, Fleming and Gehan designs. This implies that most brain tumor clinical trials are at high risk with great uncertainty in trial outcomes. Expert Rev Anticancer Ther. Semin Oncol. Optimal, minimax and admissible two-stage design for phase II oncology clinical trials. Its interesting to see that most trials without mentioning specific design types (like Simons optimal or minimax, Gehan, Fleming, or admissible designs) failed to provide one or more than one key information for the implementation results of two-stage design sample size calculation. Compressing drug development timelines in oncology using phase 0 trials. Phase 2 study of Pomalidomide (CC-4047) monotherapy for children and young adults with recurrent or progressive primary brain tumors. Intraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma. 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. Diagnosis and treatment patterns for patients with leptomeningeal metastasis from solid tumors across Europe. Clin Trials. 2014;33(12):2004-2016. 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]. Only three studies have been completed for both stages and two out of the three completed studies had shown the efficacy. The most widely used endpoints were PFS6 (n=18) and ORR (n=8) in Phase 2 single-arm trials. 2023 BioMed Central Ltd unless otherwise stated. Systemic Therapy Approaches for Breast Cancer Brain and Leptomeningeal Metastases. 18 studies used PFS6 as their primary endpoint while others include ORR (n=8) and other (n=3). Disclaimer, National Library of Medicine Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase II multicenter clinical trial. Pharm Stat. Treatment-emergent adverse events with a fatal outcome occurred in eight (6%) of 145 patients; none were considered related to loncastuximab tesirine. This site needs JavaScript to work properly. Nat Commun. 2014;1(2):345. Patients received 200 mg of pembrolizumab intravenously every 3 weeks until definitive progression or unacceptable toxicity. The .gov means its official. Detailed Description: This is an international, single-arm, multicenter phase 2 trial, in 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). The outcomes of simulation are depicted in Fig. Careers. 2022 Feb 20;41(4):786-797. doi: 10.1002/sim.9258. The median follow-up of surviving patients was 6.3 months (range, 2.2-12.5 months). PMC and transmitted securely. 2022 Oct 19;24(6):428. doi: 10.3892/ol.2022.13548. 2022 Oct;23(10):1457-1476. doi: 10.1007/s11864-022-01011-w. Epub 2022 Sep 22. Accessibility Better understanding on the study drug information and targeted molecular information might help the understanding of why the two-stage trials had been terminated after the stage 1 and ineffective after successful completion of both stages. Biostatistics. The therapeutic areas in oncology and immune-modulatory drugs were the most expensive, with a median of $2.8 billion and a mean of $4.5 billion [3]. Valemetostat 200 mg orally once Onco Targets Ther. In these cases, researchers must use endpoints like response ratethat can demonstrate clinical impact in the absence of direct comparison data. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. Muhic A, et al. 2016 Dec;34(34):4086-4093. doi: 10.1200/JCO.2016.67.7732. The Follow-Up period ends 2 years after End of Treatment. 2015;17(7):9928. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. 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. 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 Wouters and colleagues reported that U. S. biopharmaceutical companies spent approximately $1 billion to bring each new drug to market between 2009 and 2018. Wonsuk Yoo. Biometrics. Phase 2 study of bosutinib, a Src inhibitor, in adults with recurrent glioblastoma. JPA reports personal fees from ADC Therapeutics, OncLive, and Oncinfo, outside of the submitted work; and has an immediate family member who has served on advisory boards from Puma Biotechnology, Inovio Pharmaceuticals, Agios Pharmaceuticals, Forma Therapeutics, and Foundation Medicine. Please enable it to take advantage of the complete set of features! The followings were key words for the literature search as index terms or free-text words: phase II trials, glioblastoma, and two-stage design. Stat Biopharma Res. The .gov means its official. Wang et al. Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. Serious adverse events were reported in 57 (39%) of 145 patients. Article JAMA. 2021 Jan;20(1):117-128. doi: 10.1002/pst.2060. 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. sharing sensitive information, make sure youre on a federal Optimal two-stage designs for exploratory basket trials. Epub 2016 Sep 30. 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 KH, JF, SH, and YQ report personal fees from ADC Therapeutics, during the conduct of the study. Trials involving several arms, or randomized trials, treat randomly-selected groups of patients with different therapies in order to compare their medical outcomes. Unable to load your collection due to an error, Unable to load your delegates due to an error. Careers. Clin Trials. 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. Sort by Weight Alphabetically Medicine and Dentistry Patient Interpretation: 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. 2020 Aug;26(8):1309. doi: 10.1038/s41591-020-0978-1. Stat Biopharma Res. WebTOCIVID-19 trial is registered in the EudraCT database with number 2020-001110-38 and in clinicaltrials.gov with ID NCT04317092. Most trials (90%) used Simons two-stage designs. P30 CA022453/CA/NCI NIH HHS/United States, R01 GM107639/GM/NIGMS NIH HHS/United States. Terms and Conditions, Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma. Kinders R, et al. Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next? FOIA Gehan EA. Pembrolizumab in Patients With Extensive-Stage Small-Cell Lung Cancer: Results From the Phase Ib KEYNOTE-028 Study. 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. Evaluating efficacy and safety of loncastuximab tesirine injection for the treatment of adult patients with relapsed or refractory large B-cell lymphoma. Kummar S, et al. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. PMC 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]. -, Ongerboer de Visser, B. W. et al. 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. 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. The synonyms and closely related words include phase 2 for phase II trials, GBM or high-grade glioma for glioblastoma, and 2-stage, Simon, Fleming or Gehan for two-stage design. All authors reviewed the manuscript. government site. Protracted low doses of temozolomide for the treatment of patients with recurrent glioblastoma: a phase II study. 2013;113(1):12734. Epub 2019 Nov 26. Would you like email updates of new search results? Bayesian single-arm phase II trial designs with time-to-event endpoints. Biom Biostat Int J. Correspondence to Wu J, Pan H, Hsu CW. Zhou H, et al. Cancer immunotherapy trial design with cure rate and delayed treatment effect. Oncol Lett. An increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal1-3. Spatial two-stage designs for phase ii clinical trials. Sharma M, et al. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. 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. 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 Novak 2 , Erika Lerch 5 , Galle Rhyner Agocs 6 , official website and that any information you provide is encrypted This systematic review has some limitations. Jung SH, et al. Le Rhun E, Devos P, Houillier C, Cartalat S, Chinot O, Di Stefano AL, Lepage C, Reyns N, Dubois F, Weller M. Romiplostim for temozolomide-induced thrombocytopenia in glioblastoma: The PLATUM trial. 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. 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. Multicenter Phase II Study of Lenalidomide in Relapsed or Recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002. Bethesda, MD 20894, Web Policies Eastern Cooperative Oncology Group. This site needs JavaScript to work properly. 2021 Oct 12;12(1):5954. doi: 10.1038/s41467-021-25859-y. eCollection 2022. Pasqualini C, et al. IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). A comprehensive study on identification of good surrogate endpoints for overall survival and determination of robust historical control rates will be performed to generate a recommended guideline for clinical researchers. 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. 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. The response and survival of children with recurrent diffuse intrinsic pontine glioma based on phase II study of antineoplastons A10 and AS2-1 in patients with brainstem glioma. Dhakal A, Van Swearingen AED, O'Regan R, Anders CK. An International, Single-Arm, Multicenter Phase 2 Trial. Lin Y, Shih WJ. 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. Copyright 2020 Friends of Cancer Research. J Clin Oncol. Schmidt R, Faldum A, Kwiecien R. Adaptive designs for the one-sample log-rank test. 2011;11(5):65760. 2010;28(11):193641. In This phase 2 study assessed the efficacy and safety of the dual EZH1 and EZH2 inhibitor valemetostat in patients with R/R ATL. These factors are recommended to be considered carefully when planning a Phase 2 single-arm study. Salvage therapy with single agent bendamustine for recurrent glioblastoma. Spatial Two-stage Designs for Phase II Clinical Trials. Comput Stat Data Anal. Ann Oncol. Would you like email updates of new search results? OPTIM-ARTSAn adaptive phase II open platform trial design with application to a metastatic melanoma study. Why Should I Register and Submit Results? HHS Vulnerability Disclosure, Help 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. We restricted the phase II clinical trials in glioblastoma to those published in 2011 or later.

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