4). 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. Unable to load your collection due to an error, Unable to load your delegates due to an error. Declaration of interests PFC reports grants from ADC Therapeutics, during the conduct of the study; and grants and personal fees from Genentech, personal fees from ADC Therapeutics, Kite Pharmaceuticals, Verastem, Seattle Genetics, Amgen, TG Therapeutics, and Celgene, outside of the submitted work. Valemetostat 200 mg orally once The primary endpoint was safety. Kinders R, et al. https://doi.org/10.1186/s12874-022-01810-7, DOI: https://doi.org/10.1186/s12874-022-01810-7. Epub 2019 Nov 26. 2013;113(1):12734. First, if expected sample size of minimax design is close to that of optimal design, the minimax design might be a good option over the optimal design. 2022 May;169:107420. doi: 10.1016/j.csda.2021.107420. official website and that any information you provide is encrypted Reference curve sampling variability in one-sample log-rank tests. Please enable it to take advantage of the complete set of features! J Neurooncol. sharing sensitive information, make sure youre on a federal Lee EQ, et al. Before Biostatistics. For instance, in Case 3, the 10% and 50% reductions of p0 are 0.45 (=0.50.9) and 0.25 (=0.50.5). and transmitted securely. Before Tang H, et al. Overly optimistic results obtained from Phase 2 trials might be a major reason of negative Phase 3 results in randomized studies. 2021;9(4):e002114. Optimal two-stage designs for exploratory basket trials. Burzynski SR, et al. Englert S, Kieser M. Adaptive designs for single-arm phase II trials in oncology. Leveraging Molecular and Immune-Based Therapies in Leptomeningeal Metastases. 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]. 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. Thank you for submitting a comment on this article. 2009;45(5):7416. The https:// ensures that you are connecting to the 2019;85:105807. 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, 2021 Jan;20(1):117-128. doi: 10.1002/pst.2060. 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. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, 1R01CA244975-01/U.S. 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]. 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. 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. Modified Simon's minimax and optimal two-stage designs for single-arm phase II cancer clinical trials. Phase II trial of ponatinib in patients with bevacizumab-refractory glioblastoma. Muhic A, et al. An official website of the United States government. Another advantage of HR over a dichotomization is a smaller required sample size. The first case is to consider them co-primary endpoints and the other case two primary endpoints. Nat Rev Cancer. The followings were key words for the literature search as index terms or free-text words: phase II trials, glioblastoma, and two-stage design. Taylor JW, et al. 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]. 2019 Jul 2;10(42):4255-4261. doi: 10.18632/oncotarget.26981. (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)? 2020;20(1):126. 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. An International, Single-Arm, Multicenter Phase 2 Trial. Read our, ClinicalTrials.gov Identifier: NCT04560166, Interventional Childs Nerv Syst. Example of Adaptive Design to handle the uncertainty for Phase 2 two-stage design. Would you like email updates of new search results? The patients will receive irinotecan 50 mg/m2/day IV and temozolomide 100 mg/m2/day orally (both on Days 1-5) in combination with naxitamab 2.25 mg/kg/day IV (Days 2, 4, 8 and 10) (total 9 mg/kg per cycle), and GM-CSF 250 ug/m2/day sc, (Days 6-10). But interestingly almost 60% of studies (17/29, 59%) failed to provide at least one key output results of sample size calculation such as the number of samples of first stage and both stages (\({n}_{1}, n\)) and the treatment rejection numbers of the first stage and both stages (\({r}_{1}, r\)). doi: 10.1371/journal.pone.0246448. Results. Clin Trials. 2021;39(1):22631. Norden AD, et al. 2014;30(12):205161. Fleming TR. 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. Atorvastatin in combination with radiotherapy and temozolomide for glioblastoma: a prospective phase II study. Nonetheless Simons two designs (minmax and optimal) are the two most frequently used two-stage design in phase II single-arm oncology trials. Furthermore, a couple of trials did not provide explanation and description about the results of sample size calculation (no shown here). 2022 Oct 19;24(6):428. doi: 10.3892/ol.2022.13548. Glioblastoma clinical trials: current landscape and opportunities for improvement. JAMA. 2011;103(3):491501. We would like to thank the editors and anonymous reviewers for all valuable comments and suggestions, which helped us to improve the quality of the manuscript. We enrolled patients aged 18 years with HER2-positive breast cancer and newly Naxitamab and GM-CSF will be given for at least 8 cycles. Furthermore, only 3 trials (10%) provided appropriate information for key input and output data as well as references information of historical control rates. PMC 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. The unacceptable historical control rate should be a maximum rate while the acceptable expected treatment rate should be a minimum rate in order not to be overly optimistic for the Phase 2 clinical trials. Google Scholar. 1R01CA227156-01/U.S. Racine-Poon A, et al. 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. Using 2013;24(4):11129. 2019;37(15_suppl):1820618206. Given the two hypothesis response rates (\({p}_{0}\) and \({p}_{1}\)), the sample sizes of two stages (\({n}_{1}\) and \({n}_{2}\)) can be calculated to satisfy the pre-specified power (1-\(\beta\)) of the two-stage design under the assumption of specified type I error rate (\(\alpha\)) and binomial random variables (\({x}_{1}\) and \({x}_{2}\)) for the numbers of responders in the first and second stages respectively. HHS Vulnerability Disclosure, Help The author(s) read and approved the final manuscript. One-sample multiple testing procedure for phase II clinical trials. 2021 Dec;21(12):1313-1320. doi: 10.1080/14737140.2021.1988853. Stat Biopharma Res. (Yes, No), (9) reference of historical control data provided? safety; single-stage design; tolerability; toxicity; two-stage design. Phase 2 trial of dasatinib in target-selected patients with recurrent glioblastoma (RTOG 0627). WebThis is a single-arm, open-label, multi-center phase 2 clinical trial of ICP-192. An Open-Label, Single-Arm, Phase 2 Trial of Valemetostat in Relapsed or Refractory Adult T-Cell Leukemia/Lymphoma - ScienceDirect Available online 27 Epub 2015 Apr 1. The Bayesian basket design for genomic variant-driven phase II trials. 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. A treatment cycle is 21 days. Among 29 trials, only three has been completed for both stages and two studies have shown the efficacy. 2012;110(1):1118. 2015;34(16):240316. Onco Targets Ther. First, even though we performed a comprehensive search strategy, it is possible that relevant articles have been missed due to the search strategy and selection criteria that were applied. -, Wang, N., Bertalan, M. S. & Brastianos, P. K. Leptomeningeal metastasis from systemic cancer: review and update on management. Federal government websites often end in .gov or .mil. Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. 2013;111(2):20512. Kalpathy-Cramer J, et al. Treatment-emergent adverse events with a fatal outcome occurred in eight (6%) of 145 patients; none were considered related to loncastuximab tesirine. 8600 Rockville Pike 2022 Feb 20;41(4):786-797. doi: 10.1002/sim.9258. A common practice in sample size calculation is to assume that the event time in the new treatment follows exponential distribution. Leptomeningeal carcinomatosis. Finkelstein DM, Muzikansky A, Schoenfeld DA. CNS Drugs. A Bayesian basket trial design using a calibrated Bayesian hierarchical model. Analysis of survival data under the proportional hazards model. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). By using this website, you agree to our Annals of Palliative Medicine, 10, 3277-3285. We conducted the prospective, open-label, single-arm, phase 2 TUXEDO-1 trial. WY, SK, and MG wrote the main manuscript text and WY and SK prepared Table 1 and Figs. 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. 11, 561569 (1993). Disclaimer, National Library of Medicine Korean J Radiol. 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 Multistage designs for phase II clinical trials: statistical issues in cancer research. For general information, Learn About Clinical Studies. Oncotarget. J Neurooncol. 2022 May;78(5):707-719. doi: 10.1007/s00228-021-03253-3. Hematology Am Soc Hematol Educ Program. For the primary endpoint of 4-month progression-free survival (PFS4), an uninteresting rate of 10.9% obtained from historical controls and an anticipated rate of 28.9% were assumed. Silvani A, et al. GBM: glioblastoma, PFS6: progression-free survival at 6months, Key info: key input parameters for two-stage design, Right SS: did two-stage sample size calculation be appropriately implanted? Du XJ, et al. Suh CH, et al. Among examined 29 trials, 12 trials (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. Kwak M, Jung S-H. Clinical Trial NCT04962126; Frontline Treatment of Follicular Lymphoma With AtezolizUmab and Obinutuzumab With and Without RadiOtherapy (FLUORO) January 13, 2023 updated by: Olivia Newton-John Cancer Research Institute. The site is secure. Epub 2022 Apr 1. 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