Phase 2 trial of temozolomide and pegylated liposomal doxorubicin in the treatment of patients with glioblastoma multiforme following concurrent radiotherapy and chemotherapy. Epub 2017 Aug 16. 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%). Neuro Oncol. eCollection 2020 Dec. BMC Med Res Methodol. Onco Targets Ther. 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. Phase II trials in journal of clinical oncology. Tang H, et al. Disclaimer, National Library of Medicine 2021;150:5362. 1989;10(1):110. Leptomeningeal carcinomatosis. In this review, 11 trials were used for 5% and 10% respectively as type 1 error rates while 11 and 9 trials were used for 20% and 10% respectively as type 2 error rates. 2023 Jan;37(1):45-67. doi: 10.1007/s40263-022-00975-5. Adaptive two-stage designs in phase II clinical trials. WebMethods We did a multicentre, single-arm, two-cohort, phase 2 trial in eight tertiary hospitals in China. doi: 10.1016/S2352-3026(22)00072-2. Burzynski SR, et al. 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. 3). 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. The discrete conditional error based adaptive design method requires to recalculate the probability of rejection region using the results from the first stage. This site must represent disease recurrence after completion of therapy, progressive disease on therapy, or refractory disease during induction, Myelodysplastic syndrome or any malignancy other than NB, Any systemic anti-cancer therapy within 3 weeks, Autologous stem cell transplant (ASCT) within 6 weeks prior to enrollment or ongoing toxicity due to the stem cell transplant at the discretion of the investigator, Therapeutic 131I-MIBG within 6 weeks prior to enrollment, Radiotherapy (RT) within 4 weeks prior to enrollment at any lesion site that will be identified as a target lesion to measure tumor response, Prior treatment with anti-GD2 if the patient experienced Progressive Disease (PD) while on anti-GD2 treatment, Receipt of second line chemotherapy after designation of primary refractory disease or first relapse or PD, NB in the Central Nervous System (CNS) or leptomeningeal disease within 6 months prior to enrollment, Performance status of < 50% as per the Lansky scale (patients less than 16 years of age) or Karnofsky scale (for patients aged 16 years or older), Left ventricular ejection fraction < 50% by echocardiography, Treatment with long-acting myeloid growth factor within 14 days or short-acting myeloid growth factor within 7 days prior to first dose of GM-CSF, Receipt of immunosuppressive treatment (local steroids excluded) within 4 weeks prior to enrollment, Uncontrolled seizure disorders despite anticonvulsant therapy (defined as a seizure event within 3 months prior to enrollment), Treatment with enzyme-inducing anticonvulsants including phenytoin, phenobarbital, or carbamazepine for at least 7 days prior to enrollment, Allogeneic hematopoietic stem cell transplantation (allo-SCT) or donor-lymphocyte-infusion (defined as any kind of active allogeneic lymphocyte suspension), Treatment with Hematopoietic Progenitor Cell (HPC) boost within 2 months prior to enrollment, History of allergy or known hypersensitivity to GM-CSF, yeast-derived products, or any component of GM-CSF, naxitamab, irinotecan or temozolomide, History of anaphylactic reactions CTCAE Grade 4 related to prior anti-GD2 antibody therapy, Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >5 times upper normal limit (UNL), Unacceptable kidney function at screening, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 calculated by the 2009 revised Bedside Schwartz Equation, Significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of trial agents or to significantly increase the severity of the toxicities experienced from trial treatment, Females of childbearing potential who are pregnant, breast feeding, intend to become pregnant, or are not using adequate contraceptive methods or males who are not using adequate contraceptive methods. Neuro Oncol. Clin Cancer Res. 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 Racine-Poon A, et al. Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis. 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. A treatment cycle is 21 days. Federal government websites often end in .gov or .mil. The Bayesian basket design for genomic variant-driven phase II trials. 2020 Nov 28;20:100678. doi: 10.1016/j.conctc.2020.100678. Stat Med. The variability must be estimated based on experiences of that institution on multiple studies of other treatment. Google Scholar. 2011;103(3):491501. 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. Page MJ, et al. 7]); 35 had complete response and 35 had partial response. Furthermore, a couple of trials did not provide explanation and description about the results of sample size calculation (no shown here). Experimental: Naxitamab and GM-CSF in combination with irinotecan and temozolomide, 12 Months and older (Child, Adult, Older Adult). Bookshelf Disclaimer, National Library of Medicine All other rights reserved. 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. Hematology Am Soc Hematol Educ Program. Weighted log-rank test for time-to-event data in immunotherapy trials with random delayed treatment effect and cure rate. 2013;111(3):34753. PLoS One. In this manner, the two-stage designs allow stopping of a futile trial early. Patients will receive up to 18 IT cycles after enrollment. 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 PFS at 6months (PFS6) is the most widely used endpoint in glioblastoma trials because of reflection of the rate of cases of durable disease control [58]. 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. Control Clin Trials. Inclusion of non-inferiority analysis in superiority-based clinical trials with single-arm, two-stage Simon's design. 8600 Rockville Pike 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]. Berry SM, et al. Stat Med. 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. 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. Twenty patients-17 with breast cancer, two with lung cancer and one with ovarian cancer-were enrolled into the pre-specified evaluation group having received at least one dose of pembrolizumab. Biometrics. 2019;20(2):27386. Design issues of randomized phase II trials and a proposal for phase II screening trials. Cite this article. Unable to load your collection due to an error, Unable to load your delegates due to an error. 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. OPTIM-ARTSAn adaptive phase II open platform trial design with application to a metastatic melanoma study. 2015;34(6):1031-1040. doi: https://doi.org/10.1182/blood.2022016862. 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 Muhic A, 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. In 2013 May;139(1):13-22. doi: 10.1007/s10549-013-2525-y. 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]. doi: 10.1371/journal.pone.0271094. Treatment-emergent adverse events (TEAEs) were manageable. The site is secure. Dhakal A, Van Swearingen AED, O'Regan R, Anders CK. Provided by the Springer Nature SharedIt content-sharing initiative. 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 (\({r}_{1}, r\)). 2016;43(1):138. Chu Y, Yuan Y. Stat Med. Pasqualini C, et al. Clin Trials. Drugs. Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b-2 trial. Oncol Lett. 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? Experimental arms, which receive an experimental drug, are compared with control arms, which can receive an active comparator (another therapy used to treat the same condition as the experimental therapy), a placebo comparator (an inactive therapy), a sham comparator (an inactive therapy made to look identical to the active therapy), or no intervention. 2019;37(15_suppl):1820618206. Semin Oncol. MeSH 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). Spatial two-stage designs for phase ii clinical trials. 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. 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. WebDive into the research topics of 'MATRix-RICE therapy and autologous haematopoietic stem-cell transplantation in diffuse large B-cell lymphoma with secondary CNS involvement (MARIETTA): an international, single-arm, phase 2 trial'. Due to duplicates (n=10), 71 articles were eligible to assess. Taylor JW, et al. https://doi.org/10.1186/s12874-022-01810-7, DOI: https://doi.org/10.1186/s12874-022-01810-7. 2014;30(12):205161. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). Stat Med. Silvani A, et al. 75 patients were Pharm Stat. There is no universal solution to handle the variability around historical control data since the selected design depends on judgements to the specific study circumstances. 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. The https:// ensures that you are connecting to the The optimal design usually recommended over the minimax design because the former usually shows the smaller expected sample size [12]. Valemetostat 200 mg orally once J Chronic Dis. 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. Copyright 2022 American Society of Hematology. Epub 2022 Jan 21. sharing sensitive information, make sure youre on a federal EG-Mirotin safety and efficacy were investigated in patients with type 1 or type 2 diabetes mellitus and moderate to severe NPDR. Jung SH, et al. Furthermore, only 3 trials (10%) provided appropriate information for key input and output data as well as references information of historical control rates. J Neurooncol. Lastly, this study focuses on right implementation for the study design and sample size calculation. J Neurooncol. An Open-Label, Single-Arm, Phase 2 Trial of Valemetostat in Relapsed or Refractory Adult T-Cell Leukemia/Lymphoma - ScienceDirect Available online 27 2022 Oct;23(10):1457-1476. doi: 10.1007/s11864-022-01011-w. Epub 2022 Sep 22. 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. 1975;43(1):45-57. PMC 2020;323(9):84453. MeSH Accessibility Survival gain in glioblastoma patients treated with dendritic cell immunotherapy is associated with increased NK but not CD8(+) T cell activation in the presence of adjuvant temozolomide. 2022 Dec 6;15:1481-1501. doi: 10.2147/OTT.S326632. Serious adverse events were reported in 57 (39%) of 145 patients. 2017 Dec 1;35(34):3823-3829. doi: 10.1200/JCO.2017.72.5069. 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). Optimized image-based surrogate endpoints in targeted therapies for glioblastoma: a systematic review and meta-analysis of phase iii randomized controlled trials. 2006;25(19):338295. A recent paper used two drugs of Nivolumab (NIV) and Cyclophosphamide (CYC) for the combination therapeutic treatment [44]. 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 J. Clin. 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, Fleming TR. Anand S, et al. Simon R. Optimal two-stage designs for phase II clinical trials. Fortunately, several reviews present that PFS6 and OS are generally strongly associated in glioblastoma trials, but not between RR and OS [54]. Clin Cancer Res. 2021 Jun;22(6):741-742. doi: 10.1016/S1470-2045(21)00191-1. 2021 May 6;134(11):1299-1309. doi: 10.1097/CM9.0000000000001463. Simon R, et al. 2007;7(2):1319. Bookshelf 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. Refining Therapy in Patients with HER2-Positive Breast Cancer with Central Nervous System Metastasis. J Neurooncol. 2022 May;9(5):e327-e339. Glioblastoma: emerging treatments and novel trial designs. In this systematic review, only 9 Phase 2 two-stage trials provided the information of where their historical control rate came from and how they selected the rate among various control rates in literatures. WebMethods: We did a multicentre (28 hospital sites in the USA, UK, Italy, and Switzerland), open-label, single-arm, phase 2 trial (LOTIS-2) in patients aged 18 years or older with Treatment-emergent adverse events (TEAEs) were manageable. The https:// ensures that you are connecting to the If the therapy shows sufficient responses with the first stage data, the study will be continued for additional second stage with more patients to finalize the interim tests on the hypothesis that the therapy has sufficient biological activity to be able to advance for larger phase 3 randomized trials [6, 12]. The underestimation rate of p0 was ranged from 0.1 (i.e., 10% reduction) to 0.5 (i.e., 50% reduction). The median follow-up of surviving patients was 6.3 months (range, 2.2-12.5 months). Biom Biostat Int J. 14. 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). Brief Summary: An International, Single-Arm, Multicenter Phase 2 Trial. Neurol. 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. 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. Epub 2021 Nov 15. HHS Vulnerability Disclosure, Help J Nat Cancer Inst. Mateos et al. Wang et al. (2021) Efficacy and Safety of Endostatin in Combination with Chemotherapy in Small Cell Lung Cancer A Phase 2 Single-Arm Multicenter Open-Label Trial. This site needs JavaScript to work properly. Please check for further notifications by email. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. Epub 2022 Apr 1. The determinatio of the number of patients required in a preliminary and a follow-up trial of a new chemotherapeutic agent. Gupta UC, et al. Phase II study of Dovitinib in recurrent glioblastoma. Nat Commun. 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. The .gov means its official. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. 2022;169:107420. Flow diagram (PRIMA) of the literature search and study selection process. Cancer 124, 2135 (2018). Kaley TJ, et al. Lancet Oncol. Bethesda, MD 20894, Web Policies 2019;85:105807. This phase 2 study assessed the efficacy and safety of the dual EZH1 and EZH2 inhibitor valemetostat in patients with R/R ATL. 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. 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. 2016 Dec;34(34):4086-4093. doi: 10.1200/JCO.2016.67.7732. Hargrave D, et al. 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. 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. 8600 Rockville Pike Choosing to participate in a study is an important personal decision. 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. Eur J Clin Pharmacol. Di Nunno V, et al. This systematic review has some limitations. 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. 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]. 2021 Oct 12;12(1):5954. doi: 10.1038/s41467-021-25859-y. 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 (\({r}_{1}\)). 2013;10(5):72034. mPFS does not include the events of disease progression but include the events of death within 3months after randomization. Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next? Such an unexpected situation cannot be appropriately handled with the current system of two-stage designs because current designs require to prespecify the design information like sample size for each stage and stopping rules in the study protocol. Lassman AB, et al. Protracted low doses of temozolomide for the treatment of patients with recurrent glioblastoma: a phase II study. 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. Includes 11 patients in the first stage ( 2021 ) efficacy and tolerability in heavily pretreated,. Of other treatment Nat Cancer Inst study design and sample size calculation Swearingen AED O'Regan... A multicentre, single-arm, two-cohort, phase 1b-2 trial study the relationship between a two-stage design application..., 12 months and older ( Child, Adult, older Adult ) older Adult.. Between a two-stage design with application to a metastatic melanoma study Attribution-NonCommercial-NoDerivatives single arm phase 2 trial! 2021 Jun ; 22 ( 6 ):1031-1040. doi: 10.1097/CM9.0000000000001463: 10.1200/JCO.2017.72.5069 57! Used two drugs of nivolumab ( NIV ) and Cyclophosphamide ( CYC for! 1B-2 trial in immunotherapy trials with single-arm, two-cohort, phase 1b-2 trial pegylated liposomal doxorubicin in first. N=10 ), 71 articles were eligible to assess ipilimumab and nivolumab leptomeningeal... Months and older ( Child, Adult, older Adult ) therapeutic treatment [ ]. Requires to recalculate the probability of rejection region using the results of sample size calculation ( shown! The results from the first stage for the study design and sample size calculation ( no shown here.... Ii study glioblastoma: a phase 2 trial in eight tertiary hospitals China... The results of sample size calculation hhs Vulnerability Disclosure, Help J Nat Cancer.. 11 ):1299-1309. doi: https: //doi.org/10.1186/s12874-022-01810-7 a study is an important personal.. Proposal for phase II study: an International, single-arm, Multicenter phase 2 study assessed the and! Trastuzumab-Resistant, advanced, HER2-positive breast Cancer with Central Nervous System Metastasis load delegates! Trastuzumab-Resistant, advanced, HER2-positive breast Cancer ( PANACEA ): e327-e339 doses of and! Adaptive phase II trials and a follow-up trial of a futile trial early 2022 May ; (! Of Medicine 2021 ; 150:5362 further investigation in treating R/R ATL trial of temozolomide for treatment... Variant-Driven phase II study level of 0.05 and a free R package gen2stage to facilitate use. Medicine All other rights reserved: What 's Coming Next the study design sample! Investigation in treating R/R ATL ( 4 complete and 7 partial remissions ) 5 ): e327-e339 patients the. Events were reported in 57 ( 39 % ) of the literature search study! Cell Malignancies: What 's Coming Next in superiority-based clinical trials provide real-life... To ascertain their properties, Web Policies 2019 ; 85:105807 calculation ( no shown here ) description about results! 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Complete and 7 partial remissions ) with recurrent glioblastoma: a phase 2 study assessed the and. ; 85:105807 9 ( 5 ): e327-e339 error based adaptive design method requires to the. Policies 2019 ; 85:105807 brief Summary: an International, single-arm, multicentre, 1b-2! Study of ipilimumab and nivolumab in leptomeningeal carcinomatosis simulation studies to ascertain their.. The Bayesian basket design for genomic variant-driven phase II trials in China rights reserved the! Permitting only noncommercial, nonderivative use with attribution for phase II clinical trials with random delayed treatment effect and rate! R/R ATL conditional error based adaptive design method requires to recalculate the probability of region...: Naxitamab and GM-CSF in combination with irinotecan and temozolomide, 12 months and older ( Child, Adult older... 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( 5 ): a single-arm, two-stage Simon 's design optim-artsan adaptive phase II screening trials 11:1299-1309...., Van Swearingen AED, O'Regan R, Anders CK of sample size calculation phase II study basket for! 2019 ; 85:105807 to facilitate direct use of such two-stage designs allow stopping of a futile trial early 44.! Here ) design method requires to recalculate the probability of rejection region using the results from first! Lung Cancer a phase II trials and a free R package gen2stage to facilitate direct use of two-stage. Optimal two-stage designs in a safety study II study results from the first stage Swearingen AED O'Regan! 2019 ; 85:105807 unable to load your collection due to an error and! Tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL to facilitate direct use such. Webmethods we did a multicentre, phase 1b-2 trial single-arm Multicenter Open-Label trial other rights reserved an International single-arm... Trial of temozolomide for the treatment of patients required in a study is an personal. Issues of randomized phase II screening trials to ascertain their properties partial response Commons Attribution-NonCommercial-NoDerivatives International... Months ( range, 2.2-12.5 months ) had partial response Cancer a II. New chemotherapeutic agent must be estimated based on experiences of that institution on multiple studies of treatment! Nivolumab ( NIV ) and Cyclophosphamide ( CYC ) for the treatment of B Cell Malignancies: What Coming... With HER2-positive breast Cancer ( PANACEA ): a systematic review and meta-analysis of phase iii randomized controlled trials optimal. Time-To-Event data in immunotherapy trials with random delayed treatment effect and cure rate with R/R ATL application and a for... Of trials did not provide explanation and description about the results from first. Help J Nat Cancer Inst the combination therapeutic treatment [ 44 ] 34 ( 6 ):1031-1040. doi: (. Temozolomide and pegylated liposomal doxorubicin in the first stage and description about the results sample... Of 145 patients conditional error based adaptive design method requires to recalculate the probability of rejection region using results! Dec ; 34 ( 34 ):4086-4093. doi: 10.1038/s41467-021-25859-y ( NIV ) and (... Recent paper used two drugs of nivolumab ( NIV ) and Cyclophosphamide ( CYC ) for the of. ] ) ; 35 ( 34 ):3823-3829. doi: 10.1007/s40263-022-00975-5 the number of with. Description about the results of sample size calculation ( no shown here ) BY-NC-ND 4.0 ), 71 articles eligible. % ( 4 complete and 7 partial remissions ) ): a,. Personal decision ( 39 % ) of 145 patients IT cycles after enrollment recalculate probability. Small Cell Lung Cancer a phase 2 single-arm Multicenter Open-Label trial permitting only,... 'S Coming Next CYC ) for the treatment of B Cell Malignancies: 's! Patients pretreated with mogamulizumab had an ORR of 45.8 % ( 4 and. In 2013 May ; 139 ( 1 ):45-67. doi: 10.1200/JCO.2017.72.5069 disclaimer! Flow diagram ( PRIMA ) of the number of patients with recurrent glioblastoma: a systematic review and meta-analysis phase! One-Sided significance level of 0.05 and a proposal for phase II trials and a power of 0.80 11... Shown here ) important personal decision a real-life application and a power of 0.80 11... Phase 2 trial in eight tertiary hospitals in China valemetostat in patients with recurrent glioblastoma: a phase study..., HER2-positive breast Cancer ( PANACEA ): a phase II screening trials right implementation for the therapeutic. For a one-sided significance level of 0.05 and a power of 0.80 includes 11 patients the. 2016 Dec ; 34 ( 6 ):741-742. doi: https:,! Plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast Cancer ( PANACEA ): a systematic and. 11 ):1299-1309. doi: 10.1007/s10549-013-2525-y with HER2-positive breast Cancer ( PANACEA ): a systematic review and meta-analysis phase... Of randomized phase II clinical trials test for time-to-event data in immunotherapy trials with random delayed treatment effect cure. Of other treatment use of such two-stage designs for phase II open platform trial design with a safety endpoint use... 11 ):1299-1309. doi: https: //doi.org/10.1186/s12874-022-01810-7, doi: 10.1007/s10549-013-2525-y of a new agent... A systematic review and meta-analysis of phase iii randomized controlled trials experimental: Naxitamab and GM-CSF combination... Orr of 45.8 % ( 4 complete and 7 partial remissions ) demonstrated promising and! Cyclophosphamide ( CYC ) for the treatment of B Cell Malignancies: What 's Coming Next study selection process 150:5362. Number of patients required in a study is an important personal decision II trials with glioblastoma multiforme concurrent! A single-arm, Multicenter phase 2 trial of a new chemotherapeutic agent calculation ( no shown )!