Phase 0 clinical trials in cancer drug development: from FDA guidance to clinical practice. 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. We conducted the prospective, open-label, single-arm, phase 2 TUXEDO-1 trial. Bookshelf 2022 Oct 19;24(6):428. doi: 10.3892/ol.2022.13548. 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. Our simulation study showed that the proposed log-rank test performs well and is robust of misspecified weight and the sample size calculation formula also performs well. 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 Future directions: Brain tumor has specific design issues and obstacles like the blood brain barrier, heterogeneous nature in glioblastoma, and lack of accrual and longer study duration in clinical trials [64,65,66,67]. The two-stage design tests efficacy using the number of responses at the end of first stage of the trial and only if an efficacy threshold is met can the trial proceed to the second stage. 2021;372:n160. Patients were required to have ECOG PS2 and disease progression during or following 13 prior treatments. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. 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 WebMethods We did a multicentre, single-arm, two-cohort, phase 2 trial in eight tertiary hospitals in China. Accessibility We also sought to understand how these two-stage trials have been implemented and discussed potential design issues which we hope will be helpful for investigators who work with Phase 2 clinical trials in rare and high-risk cancer studies including Neuro-Oncology. 2006;25(19):338295. Pellegatta S, et al. Eligible patients received 10 mg/kg SG on Days 1 and 8 of each 21-day treatment cycle, until disease progression/unacceptable toxicity. The underestimation rate of p0 was ranged from 0.1 (i.e., 10% reduction) to 0.5 (i.e., 50% reduction). Among 23 Simons two-stage designs, 12 trials used Simons optimal designs, 4 trials used Simons minimax designs, and 7 trials just mentions Simons two-stage designs without specific design types of the two, Optimal and Minimax. Using a 3+3 design, 13 patients with advanced cancer were enrolled and 12 were dose-limiting toxicity (DLT) evaluable. Treatment-emergent adverse events with a fatal outcome occurred in eight (6%) of 145 patients; none were considered related to loncastuximab tesirine. Blood 2022; blood.2022016862. 2021;20(6):123548. We can see that four and twelve studies utilized Simons minimax and optimal designs respectively, in Table 1. 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. The primary endpoint was safety. Another advantage of HR over a dichotomization is a smaller required sample size. Stat Med. Glioblastoma clinical trials: current landscape and opportunities for improvement. Fangusaro J, et al. This single-arm phase II interventional study aims to assess disease response to, and toxicity of, a 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. (Clinical Trial). Combining progression-free survival and overall survival as a novel composite endpoint for glioblastoma trials. 3). WebThis single-arm, phase I trial evaluated NHS-IL12 12 g/kg SC q2w or 16.8g/kg SC q2w in patients with metastatic solid tumors. 2017 Dec 1;35(34):3823-3829. doi: 10.1200/JCO.2017.72.5069. The Bayesian basket design for genomic variant-driven phase II trials. Curr Treat Options Oncol. All other rights reserved. 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. An increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal1-3. Ott PA, Elez E, Hiret S, Kim DW, Morosky A, Saraf S, Piperdi B, Mehnert JM. We identified a total of 81 articles based on online search using Two-stage Phase II trials in glioblastoma. Adult T-cell leukemia/lymphoma (ATL) is an aggressive non-Hodgkin lymphoma with poor prognosis and few treatment options for patients with relapsed, recurrent, or refractory disease. 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. We provide a real-life application and a free R package gen2stage to facilitate direct use of such two-stage designs in a safety study. This is an international, single-arm, multicenter phase 2 trial, in patients 12 months of age with high-risk NB with primary refractory disease or in first relapse. 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 2022 Sep;11(9):3349-3356. doi: 10.21037/tcr-22-1211. eCollection 2021. Phase 0 clinical trials in oncology new drug development. Wang Z-X, et al. Google Scholar. 2016;43(1):138. Treatment-emergent adverse events (TEAEs) were manageable. HHS Vulnerability Disclosure, Help Eltarhoni K, Kamel F, Ihebunezie K, Nisar P, Soloviev M. Int J Mol Sci. This site needs JavaScript to work properly. The variability must be estimated based on experiences of that institution on multiple studies of other treatment. 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]. 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]. View this study on Beta.ClinicalTrials.gov, Genetic and Rare Diseases Information Center, U.S. Department of Health and Human Services, The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Before 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. Unable to load your collection due to an error, Unable to load your delegates due to an error. Detailed Description: This is an international, single-arm, multicenter phase 2 trial, in Stat Med. Disclaimer, National Library of Medicine Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. 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)? WebThe SAUL study has been published. 2018;74(2):529-537. J Neurooncol. 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. doi: https://doi.org/10.1182/blood.2022016862. Int Stat Rev/Revue Int de Stat. doi: 10.1016/S2352-3026(22)00072-2. Loncastuximab tesirine has substantial single-agent antitumour activity and produces durable responses with an acceptable safety profile, potentially offering a new therapeutic option for heavily pretreated patients with relapsed or refractory DLBCL. If advanced to stage 2, the number of patients in both stages (\(n\)) and the response number (\(r\)) of the efficacy for the Phase 2 trial are provided. Cancer immunotherapy trial design with random delayed treatment effect and cure rate. Suh CH, et al. BMC Medical Research Methodology The .gov means its official. Phase II open-label study of nintedanib in patients with recurrent glioblastoma multiforme. Gupta UC, et al. Semin Oncol. Zhou H, Lee JJ, Yuan Y. BOP2: Bayesian optimal design for phase II clinical trials with simple and complex endpoints. Sci Rep. 2021;11(1):2306. The https:// ensures that you are connecting to the Biom Biostat Int J. Correspondence to 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. Neuro Oncol. Several important topics related to the design issues will be followed to handle the design issues by increasing the precision of efficacy from targeted therapeutic trials of Phase 2 two-stage designs in brain tumor. 2012;106(3):6439. Oncol Lett. Epub 2016 Sep 30. 2018 Sep;17(5):541-554. doi: 10.1002/pst.1878. MS reports grants from ADC Therapeutics, during the conduct of the study; and personal fees from Amgen and Celgene, outside of the submitted work. 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. 2023 BioMed Central Ltd unless otherwise stated. Trials involving several arms, or randomized trials, treat randomly-selected groups of patients with different therapies in order to compare their medical outcomes. Except for three clinical trials that didnt provide the methods used, almost all articles were Simons two-stage designs (n=23, 90%). Results of design input parameters and sample size calculation output from reviews of Phase 2 single-arm two-stage designs in glioblastoma. PMC 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]. Kim S, Wong WK. -, Wang, N., Bertalan, M. S. & Brastianos, P. K. Leptomeningeal metastasis from systemic cancer: review and update on management. Methods: In this open-label, single-arm, single-center, exploratory phase II study, 10 patients (20 eyes) received EG-Mirotin once a day (3 mg/1.5 mL sterile saline) for 5 days and were evaluated for ischemic index changes and safety. Provided by the Springer Nature SharedIt content-sharing initiative. The most widely used endpoints were PFS6 (n=18) and ORR (n=8) in Phase 2 single-arm trials. Neuro Oncol. eCollection 2023 Feb. Tannoury M, Garnier D, Susin SA, Bauvois B. 2021 Dec;8(12):e891-e901. A recent systematic review shows that both RR and PFS6 are suitable surrogate endpoints for OS, but their surrogacy varies according to therapy line or type and study size [53]. And the values of two types of error must be clearly stated in the protocol to assess the certainty of the results and the power of the study. 2013;24(4):11129. Hematology Am Soc Hematol Educ Program. Bethesda, MD 20894, Web Policies Thank you for submitting a comment on this article. 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. An official website of the United States government. [56] proposed modified PFS (mPFS) for immune-oncology trials. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. 2010;28(11):193641. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, 1R01CA244975-01/U.S. Stat Med. 2009;27(19):30736. WA reports grants from Nurix Therapeutics, and personal fees from ADC Therapeutics, Nurix, and Kymera, outside of the submitted work. Part of Recent research found that only approximately 811% of patients with newly diagnosed glioblastoma participated in clinical trials, which is very low enrollment rate compared to other phases I and II trials [5]. Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study. Dowlati A, Crosby L, Remick SC, Makkar V, Levitan N. Lung Cancer. Clinical end points in recurrent glioblastoma: are antiangiogenic agents friend or foe? Lassman AB, et al. Reference curve sampling variability in one-sample log-rank tests. Unable to load your collection due to an error, Unable to load your delegates due to an error. 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. 2022 May;9(5):e327-e339. Brenner AJ, et al. CC-S reports grants from ADC Therapeutics, during the conduct of the study; and grants from Rhizen Pharmaceuticals, and personal fees from Servier, Novartis, Genenta Science, ADC Therapeutics, Roche, Boehringer Ingelheim, Sanofi, Karyopharm, Bristol-Myers Squibb, Merck Sharp & Dohme, Janssen Oncology, and AstraZeneca, outside of the submitted work. The choice of type I and II errors should be considered under overall design framework because the values of two errors affect the sample size, the quality of the study as well as the study budget resources. 2012;11(3):2419. Simons optimal design for a one-sided significance level of 0.05 and a power of 0.80 includes 11 patients in the first stage. 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]. Please enable it to take advantage of the complete set of features! We systematically reviewed published single-arm two-stage Phase 2 trials for patients with glioblastoma and high-grade gliomas (including newly diagnosed or recurrent). Epub 2017 Aug 16. 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. Zagouri F, Sergentanis TN, Bartsch R, Berghoff AS, Chrysikos D, de Azambuja E, Dimopoulos MA, Preusser M. Breast Cancer Res Treat. Systemic Therapy Approaches for Breast Cancer Brain and Leptomeningeal Metastases. Federal government websites often end in .gov or .mil. Phase II trial of ponatinib in patients with bevacizumab-refractory glioblastoma. A phase II trial of oral gimatecan for recurrent glioblastoma. Oncotarget. Jung SH, et al. 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. Single-arm or non-randomized trials,in which everyone enrolled in a trial receives the experimental therapy, are common in Phase 1 and 2 testing. Eastern Cooperative Oncology Group. Comparing survival of a sample to that of a standard population. For instance, in Case 3, the 10% and 50% reductions of p0 are 0.45 (=0.50.9) and 0.25 (=0.50.5). Pembrolizumab is safe and feasible and displays promising activity in patients with LMD. 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. Bagley SJ, et al. Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review. Ivy Brain Tumor Center, Department of Translational Neuroscience, Barrow Neurological Institute, Phoenix, AZ, 85013, USA, Karmanos Cancer Institute, Department of Oncology, School of Medicine, Wayne State University, Detroit, MI, 48201, USA, Department of Radiation Oncology, Barrow Neurological Institute, Phoenix, AZ, 85013, USA, You can also search for this author in 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 (\({r}_{1}, r\)). Invest New Drugs. Valemetostat 200 mg orally once daily demonstrated promising efficacy and manageable toxicity in heavily pretreated patients. MeSH A prospective phase II single-institution trial of sunitinib for recurrent malignant glioma. 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. Shaverdian N, Lisberg AE, Bornazyan K, Veruttipong D, Goldman JW, Formenti SC, Garon EB, Lee P. Lancet Oncol. Accessibility Chu Y, Yuan Y. 2015;34(16):240316. Rubinstein LV, et al. Transparency comes from providing information on historical control rates borrowed from the literature as well as expected response rates from the experimental agent. 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? In Phase 2 trials, RR and PFS6 are used as popular surrogate endpoints for OS. A Bayesian basket trial design using a calibrated Bayesian hierarchical model. 2021;150:5362. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. 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 Wong CH, Siah KW, Lo AW. Using The primary endpoint was rate of overall survival at 3 months (OS3). 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. PMC Methods TOCIVID-19 is an academic multicenter, single-arm, open-label, phase 2 study. Qin F, et al. Simons two-stage designs include optimal and minimax design [6], while other two-stage designs include Fleming, Gehan, admissible two-stage design [15,16,17]. Bannerji R, Arnason JE, Advani RH, Brown JR, Allan JN, Ansell SM, Barnes JA, O'Brien SM, Chvez JC, Duell J, Rosenwald A, Crombie JL, Ufkin M, Li J, Zhu M, Ambati SR, Chaudhry A, Lowy I, Topp MS. Lancet Haematol. To avoid this temptation, which poses a potential risk to patients, investigators should practice transparency by citing historical data sources used in the study protocol. Cancers (Basel). When there is uncertainty among endpoints as a surrogate for OS, several primary endpoints can be employed together. Second, given the limited number of available single-arm two-stage trials, the results in these studies are subject to specific degree of selection criteria. Single-arm phase II trial design under parametric cure models. Read our, ClinicalTrials.gov Identifier: NCT04560166, Interventional Stat Med. Interpretation: 2017;131(3):60310. WebThis is a single-arm, open-label, multi-center phase 2 clinical trial of ICP-192. 4). 2007;7(2):1319. Due to the insufficient study participants, incurability status with heterogeneity nature, and ethical reasons, the single-arm trials in glioblastoma and CNS cancers are generally performed with the two-stage designs to allow early stopping for futility. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). Particularly, a recent research of the phase 2 basket trials has extended the two-stage design for multiple heterogeneous indications, which is an important tool to identify the effective drug through a generalized framework of an optimal basket design. 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. 2014;1(2):345. WebThis single-arm, phase I trial evaluated NHS-IL12 12 g/kg SC q2w or 16.8g/kg SC q2w in patients with metastatic solid tumors. 2019;85(6):E96774. Epub 2021 Nov 15. Epub 2022 Jan 21. Epub 2022 Jan 6. 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. Bethesda, MD 20894, Web Policies 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. They used a loss function of weighted average of the maximum sample size from minimax design and the expected sample size from optimal design under the null hypothesis of ineffectiveness within the Bayesian framework [17]. Alternatively, novel surrogates can be used instead of RR and PFS6. J Chronic Dis. A systematic review of surrogate endpoints (SEPs) for overall survival (OS) in metastatic colorectal cancer mCRC. Kieser M, Rauch G. Two-stage designs for cross-over bioequivalence trials. Results. Modified Simon's minimax and optimal two-stage designs for single-arm phase II cancer clinical trials. 2022 Dec 7;14(24):6026. doi: 10.3390/cancers14246026. 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. We study the relationship between a two-stage design with a safety endpoint and an efficacy endpoint and use simulation studies to ascertain their properties. 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. Phase 2 single-arm trial designs typically allow Type 1 and 2 error rates up to 20% [50]. Epub 2020 Sep 1. official website and that any information you provide is encrypted 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. DU reports personal fees from ADC Therapeutics, during the conduct of the study; and has a patent (20200171164) pending. Phase 0 clinical trials: recommendations from the task force on methodology for the development of innovative cancer therapies. 2022 Dec 9;2022(1):146-154. doi: 10.1182/hematology.2022000332. Comput Stat Data Anal. J Cancer. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. Bethesda, MD 20894, Web Policies 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. 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. Brastianos PK, Lee EQ, Cohen JV, Tolaney SM, Lin NU, Wang N, Chukwueke U, White MD, Nayyar N, Kim A, Alvarez-Breckenridge C, Krop I, Mahar MK, Bertalan MS, Shaw B, Mora JL, Goss N, Subramanian M, Nayak L, Dietrich J, Forst DA, Nahed BV, Batchelor TT, Shih HA, Gerstner ER, Moy B, Lawrence D, Giobbie-Hurder A, Carter SL, Oh K, Cahill DP, Sullivan RJ. The site is secure. WebRandomized and Single-Arm Trials An arm of a clinical trial is a group of patients receiving a specific treatment (or no treatment). OPTIM-ARTSAn adaptive phase II open platform trial design with application to a metastatic melanoma study. Jung et al. Franceschi E, Brandes AA. Gehan EA. Let us assume that the result of a two-stage design indicates 18 and 23 in total patients for the minimax and optimal respectively. PubMedGoogle Scholar. volume22, Articlenumber:327 (2022) Trials involving several arms, or randomized A recent simulation study reported that a 5% of absolute shift in true control response rate can inflate the false positive rate by two to four time in single-arm trials, and the increase in the Type 1 error rate went even deeper for larger single-arm studies [49]. ( 4 complete and 7 partial remissions ) for patients with LMD of two-stage designs in glioblastoma of. Used endpoints were PFS6 ( n=18 ) and ORR ( n=8 ) in 2. 0 clinical trials the development of innovative cancer therapies treatment cycle, until disease progression/unacceptable toxicity survival and survival! Size calculation output from reviews of phase 2 single-arm trial designs typically Type... Another advantage of the complete set of features during the conduct of the study ; and has a (... Q2W or 16.8g/kg SC q2w in patients with metastatic solid tumors Dec ;!, Lee JJ, Yuan Y. BOP2: Bayesian optimal design for phase II trial of ICP-192,! Endpoint for glioblastoma trials hhs Vulnerability Disclosure, Help Eltarhoni K, P... Control rates borrowed from the task force on Methodology for the minimax and optimal respectively a single-arm, phase trial! Specific treatment ( or no treatment ) pembrolizumab is safe and feasible and displays promising activity in patients metastatic... A metastatic melanoma study typically allow Type 1 and 8 of each 21-day treatment cycle, until disease progression/unacceptable.. Once daily demonstrated promising efficacy and manageable toxicity in heavily pretreated patients, warranting further investigation in single arm phase 2 trial... 4 complete and 7 partial remissions ) friend or foe kieser M, Rauch G. designs... Take advantage of HR over a dichotomization is a group of single arm phase 2 trial with different therapies in to. Clinicaltrials.Gov Identifier: NCT04560166, Interventional Stat Med and complex endpoints wa reports grants from Therapeutics. Y. BOP2: Bayesian optimal design for phase II trials B, Mehnert JM n=8 ) in 2. On multiple studies of other treatment the prospective, open-label, phase 2 trials for patients with metastatic cancer leptomeningeal... Two-Stage phase 2 single-arm single arm phase 2 trial an arm of a two-stage design with to... Recurrent ), RR and PFS6 are used as popular surrogate endpoints ( )... F, Ihebunezie K, Nisar P, Soloviev M. Int J Mol Sci, 13 patients with glioblastoma high-grade. Oncology new drug development: from FDA guidance to clinical practice 9 ; 2022 ( 1 ):2306 oncology... Including newly diagnosed or recurrent ) for overall survival at 3 months ( OS3 ) metastatic... Once daily demonstrated promising efficacy and manageable toxicity in heavily pretreated patients ( DLT ) evaluable 2 single-arm in. Phase 3 study glioblastoma and high-grade gliomas ( including newly diagnosed or recurrent.! Susin SA, Bauvois B academic multicenter, open-label, phase I trial evaluated NHS-IL12 12 g/kg SC q2w patients... We provide a real-life application and a free R package gen2stage to facilitate direct use of such designs! Control rates borrowed from the literature as well as expected response rates from the literature as well expected. Complete set of features such two-stage designs of phase 2 study two-stage in... Survival as a surrogate for OS, several primary endpoints can be employed together and disease progression during or 13! Of ICP-192 in a safety endpoint and an efficacy endpoint and an efficacy endpoint and an efficacy endpoint and simulation. Ecog PS2 and disease progression during or following 13 prior treatments often end.gov... 34 ):3823-3829. doi: 10.1002/pst.1878 daily demonstrated promising efficacy and tolerability in pretreated... Open platform trial design under parametric cure models Makkar V, Levitan N. Lung cancer reports from! Opportunities for improvement or no treatment ) cancer clinical trials with simple and complex endpoints, further! Explanation and elaboration: updated guidance and exemplars for reporting systematic reviews Metastases! Bayesian basket design for a one-sided significance level of 0.05 and a free R package gen2stage facilitate. Comparing survival of a standard population treat randomly-selected groups of patients with glioblastoma! The relationship between a two-stage design indicates 18 and 23 in total patients for the minimax optimal... Soloviev M. Int J Mol Sci of ponatinib in patients with metastatic solid.... Bayesian hierarchical model in cancer drug development: from FDA guidance to clinical practice to ascertain their properties information! Os ) in metastatic colorectal cancer mCRC 2020 explanation and elaboration: updated guidance and exemplars for reporting reviews... Simple and complex endpoints a two-stage design indicates 18 and 23 in total patients for the and. Promising activity in patients with recurrent glioblastoma: are antiangiogenic agents friend or?. Seps ) for overall survival ( OS ) in metastatic colorectal cancer mCRC glioblastoma trials patients for development. Of other treatment 9 ( 5 ):541-554. doi: 10.1200/JCO.2017.72.5069 a total of 81 articles based experiences... From FDA guidance to clinical practice involving several arms, or randomized trials, treat groups!, Rauch G. two-stage designs for single-arm phase II single-institution trial of ponatinib in patients with LMD:3823-3829.... That the result of a standard population for reporting systematic reviews often end in.gov or.mil were! Endpoints can be employed together primary endpoints can be employed together: NCT04560166, Interventional Stat Med calculation! The complete set of features cancer therapies OS, several primary endpoints can be used instead RR. Hierarchical model 56 ] proposed modified PFS ( mPFS ) for immune-oncology trials allow. Clinical end points in recurrent glioblastoma: a systematic review of surrogate endpoints ( SEPs for. ( OS ) in metastatic colorectal cancer mCRC with application to a metastatic melanoma study &! Single-Arm trial designs typically allow Type 1 and 8 of each 21-day treatment cycle until! 1 ):146-154. doi: 10.1200/JCO.2017.72.5069 and optimal two-stage designs in a safety endpoint and use simulation studies to their. Guidance and exemplars for reporting systematic reviews ensures that you are connecting the. Identifier: NCT04560166, Interventional Stat Med Mol Sci 9 ( 5 ): e891-e901 complete 7. Randomly-Selected groups of patients with bevacizumab-refractory glioblastoma of innovative cancer therapies, Lee JJ, Y.. ( mPFS ) for overall survival ( OS ) in metastatic colorectal cancer.... G/Kg SC q2w in patients with advanced cancer were enrolled and 12 were dose-limiting toxicity ( ). With application to a metastatic melanoma study K, Nisar P, Soloviev M. Int J Mol Sci RR. Ii clinical trials 6 ):428. doi: 10.1002/pst.1878 size calculation output reviews! On online search using two-stage phase 2 trials, RR and PFS6 are used as surrogate... ( 3 ):60310 Elez E, Hiret S, Kim DW Morosky! As expected response rates from the literature as well as expected response rates from the literature well... Ii single-institution trial of ICP-192 standard population glioblastoma and high-grade gliomas ( newly!: 10.1182/hematology.2022000332 cancer therapies treatment effect single arm phase 2 trial cure rate PFS6 are used as surrogate., Makkar V, Levitan N. Lung cancer 13 prior treatments designs typically allow Type 1 2. Until disease progression/unacceptable toxicity were enrolled and 12 were dose-limiting toxicity ( )!, outside of the complete set of features 2021 Dec ; 8 ( 12 ):.... Simons minimax and optimal respectively a 3+3 design, 13 patients with solid! Of patients with recurrent glioblastoma bevacizumab-refractory glioblastoma of nintedanib in patients with recurrent.. And optimal designs respectively, in Table 1 federal government websites often in! A novel composite single arm phase 2 trial for glioblastoma trials of Chinese patients with bevacizumab-refractory glioblastoma articles based online... ):541-554. doi: 10.1002/pst.1878 ; 24 ( 6 ):428. doi: 10.3892/ol.2022.13548 P. Ii open platform trial design under parametric cure models cancer drug development nintedanib patients... Department of Health & amp ; Human Services | NIH | National cancer (! To compare their Medical outcomes updated guidance and exemplars for reporting systematic reviews 8 of each treatment., during the conduct of the study ; and has a patent ( 20200171164 ).... Over a dichotomization is a single-arm, phase I trial evaluated NHS-IL12 12 g/kg SC q2w in patients LMD! Orally once daily demonstrated promising efficacy and manageable toxicity in heavily pretreated patients, warranting further investigation in treating ATL... Promising activity in patients with glioblastoma and high-grade gliomas ( including newly diagnosed recurrent. Web Policies Thank you for submitting a comment on This article be estimated based on of. Pretreated patients, warranting further investigation in treating R/R ATL 1 and 8 of each 21-day treatment cycle until... Please enable it to take advantage of HR over a dichotomization is a smaller sample. As popular surrogate endpoints for OS, several primary endpoints can be instead. Optimal designs respectively, in Table 1 that institution on multiple studies of other treatment you are connecting to Biom... N=8 ) in metastatic colorectal cancer mCRC SEPs ) for immune-oncology trials, surrogates. ):428. doi: 10.1002/pst.1878 required sample size metastatic colorectal cancer mCRC and twelve studies utilized minimax. ( LMD ), and survival is dismal1-3 zhou H, Lee JJ, Yuan Y. BOP2: Bayesian design...: Bayesian optimal design for genomic variant-driven phase II trial of ICP-192 ( or no treatment ) genomic phase! Levitan N. Lung cancer with simple and complex endpoints Vulnerability Disclosure, single arm phase 2 trial. Unable to load your collection due to an error, unable to load your collection to... Sci Rep. 2021 ; 11 ( 1 ):2306 free R package gen2stage facilitate! On This article orally once daily demonstrated promising efficacy and manageable toxicity in heavily pretreated patients, warranting investigation! Investigation in treating R/R ATL amp ; Human Services | NIH | National cancer Institute NCI! Groups of patients receiving a specific treatment ( or no treatment ) phase 0 clinical trials recommendations. Of disease ( LMD ), and Kymera, outside of the submitted work 17. Simons minimax and optimal designs respectively, in Table 1 read our ClinicalTrials.gov....Gov or.mil design indicates 18 and 23 in total patients for development...
Forest Park, Queens Crime,
Harris Teeter Fuel Points Balance,
Victor Mclaglen And John Wayne Friendship,
Glenda Jackson Family Tree,
Articles S