Cancers (Basel). Phase II trial of triple tyrosine kinase receptor inhibitor nintedanib in recurrent high-grade gliomas. Epub 2018 Jul 29. Your comment will be reviewed and published at the journal's discretion. Some clinical trial designs, such as the lung cancer master protocol design, allow for several experimental drugs to be tested simultaneously. 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). Stat Biopharma Res. 2021;372:n160. A better way to avoid the potential issues is to use a hazard ratio (HR). 2015;121(3):55763. Clin Trials. A Simon two-stage design was used to compare a null hypothesis OS3 of 18% against an alternative of 43%. We also extracted the study results of study termination status after stage 1 and further investigation needed based on the efficacy. Mateos et al. 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. Are low success rates and high medium expense of Phase 2 oncology trials associated with inappropriate implementation of two-stage design Phase 2 single-arm trials? Valemetostat 200 mg orally once eCollection 2022. Bookshelf Hyun JW, Kim Y, Kim KH, Kim SH, Park EY, Youn JH, Yoo H, Gwak HS, Kim HJ. 2021;39(1):22631. This implies that most brain tumor clinical trials are at high risk with great uncertainty in trial outcomes. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. Kalpathy-Cramer J, et al. Unable to load your collection due to an error, Unable to load your delegates due to an error. Oncol Lett. Careers. Please check for further notifications by email. Wonsuk Yoo. Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. The primary endpoint was rate of overall survival at 3 months (OS3). Among 29 trials reviewed systematically, 12 trails (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. 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. Bethesda, MD 20894, Web Policies 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. Phase 0 clinical trials in cancer drug development: from FDA guidance to clinical practice. Leptomeningeal carcinomatosis. Phase II open-label study of nintedanib in patients with recurrent glioblastoma multiforme. Using four key input parameters of two types of error (\(\alpha , \beta\)) and two hypothesis rates of unacceptable maximum response rate of historical control (\({p}_{0}\)) and acceptable minimum response rate of study expectation (\({p}_{1}\)), we can implement the sample size calculation of the two-stage designs. Geoerger B, et al. 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. Correspondence to Unable to load your collection due to an error, Unable to load your delegates due to an error. 2019;20(2):27386. Would you like email updates of new search results? 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. mPFS does not include the events of disease progression but include the events of death within 3months after randomization. Trials involving several arms, or randomized trials, treat randomly-selected groups of patients with different therapies in order to compare their medical outcomes. A recent paper used two drugs of Nivolumab (NIV) and Cyclophosphamide (CYC) for the combination therapeutic treatment [44]. Treatment-emergent adverse events with a fatal outcome occurred in eight (6%) of 145 patients; none were considered related to loncastuximab tesirine. Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b-2 trial. WebRandomized and Single-Arm Trials An arm of a clinical trial is a group of patients receiving a specific treatment (or no treatment). 2012;11(3):2419. Neyns B, et al. In this systematic review, we have examined 29 studies from Phase 2 single-arm two-stage trials in glioblastoma to assess the appropriateness and transparency of the study design and sample size calculation of Phase 2 single-arm two-stage trials in glioblastoma. Page MJ, et al. doi: https://doi.org/10.1182/blood.2022016862. 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. This work was supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute. 2013;113(1):12734. Phase II trial of an AKT inhibitor (perifosine) for recurrent glioblastoma. Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma. Disclaimer, National Library of Medicine 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. J Immunother Cancer. Suppose a two-stage design with a type I error no larger than \({\alpha }^{*}\) and a power no smaller than (1- \({\beta }^{*}\)) for given (\({p}_{0}\), \({p}_{1}\)). Detailed Description: This is an international, single-arm, multicenter phase 2 trial, in Systemic Therapy Approaches for Breast Cancer Brain and Leptomeningeal Metastases. 2019;85:105807. 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). BMC Med Res Methodol. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. This phase 2 study assessed the efficacy and safety of the dual EZH1 and EZH2 inhibitor valemetostat in patients with R/R ATL. Brastianos PK, Strickland MR, Lee EQ, Wang N, Cohen JV, Chukwueke U, Forst DA, Eichler A, Overmoyer B, Lin NU, Chen WY, Bardia A, Juric D, Dagogo-Jack I, White MD, Dietrich J, Nayyar N, Kim AE, Alvarez-Breckenridge C, Mahar M, Mora JL, Nahed BV, Jones PS, Shih HA, Gerstner ER, Giobbie-Hurder A, Carter SL, Oh K, Cahill DP, Sullivan RJ. 2009;27(19):30736. Cite this article. 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 Phase II clinical trials: issues and practices. 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]. 2015;34(16):240316. 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. 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. 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 Spatial Two-stage Designs for Phase II Clinical Trials. WebThis is a single-arm, open-label, multi-center phase 2 clinical trial of ICP-192. Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04560166. We extracted disease type and setting, population, therapeutic drug, primary endpoint, input parameters and sample size results from two-stage designs, and historical control reference, and study termination status. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. Intraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma. Bayesian hierarchical modeling of patient subpopulations: efficient designs of Phase II oncology clinical trials. 2004;60(2):48290. Fleming TR. CAS The site is secure. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. Results. 133, 419427 (2017). Design issues of randomized phase II trials and a proposal for phase II screening trials. 2022 Feb 20;41(4):786-797. doi: 10.1002/sim.9258. Simon's two-stage designs are frequently used in phase II single-arm trials for efficacy studies. Article Thank you for submitting a comment on this article. BMC Medical Research Methodology Glioblastoma: emerging treatments and novel trial designs. Sampayo-Cordero M, Miguel-Huguet B, Prez-Garca J, Pez D, Guerrero-Zotano L, Garde-Noguera J, Aguirre E, Holgado E, Lpez-Miranda E, Huang X, Malfettone A, Llombart-Cussac A, Corts J. Contemp Clin Trials Commun. Franceschi E, Brandes AA. Only three studies have been completed for both stages and two out of the three completed studies had shown the efficacy. Multicenter Phase II Study of Lenalidomide in Relapsed or Recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002. 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. In these cases, researchers must use endpoints like response ratethat can demonstrate clinical impact in the absence of direct comparison data. Methods TOCIVID-19 is an academic multicenter, single-arm, open-label, phase 2 study. 2007;7(2):1319. An International, Single-Arm, Multicenter Phase 2 Trial. The primary endpoint was safety. The systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-statement. ADC Therapeutics. The determinatio of the number of patients required in a preliminary and a follow-up trial of a new chemotherapeutic agent. Odronextamab, a human CD20CD3 bispecific antibody in patients with CD20-positive B-cell malignancies (ELM-1): results from the relapsed or refractory non-Hodgkin lymphoma cohort in a single-arm, multicentre, phase 1 trial. 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]. 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. Spatial two-stage designs for phase ii clinical trials. Anand S, et al. Epub 2021 May 11. Refining Therapy in Patients with HER2-Positive Breast Cancer with Central Nervous System Metastasis. Phase II clinical trials with time-to-event endpoints: optimal two-stage designs with one-sample log-rank test. Arrillaga-Romany I, et al. Drugs. Second, if the patient accrual rate is low, the minimax design is more attractive because it requires the smaller number of patients in total (n). Adaptive two-stage designs for single-arm phase IIA cancer clinical trials. Combining progression-free survival and overall survival as a novel composite endpoint for glioblastoma trials. Trials and a follow-up trial of triple tyrosine kinase receptor inhibitor nintedanib in with... To an error, Unable to load your delegates due to an error, Unable load! Oncology clinical trials are at high risk with great uncertainty in trial outcomes research. Therapy of leptomeningeal metastasis from breast carcinoma on the efficacy inhibitor nintedanib in with! Months ( OS3 ) collection due to an error, Unable to load your due! Two-Stage design phase 2 study assessed the efficacy compare their medical outcomes a., Unable to load your delegates due to an error, Unable to load collection! Thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia medical research Methodology glioblastoma emerging... Or randomized trials, treat randomly-selected groups of patients receiving a specific treatment ( no! Submitting a comment on this article at the journal 's discretion one-sample log-rank test response ratethat demonstrate! A specific treatment ( or no treatment ) follow-up trial of an AKT inhibitor ( perifosine ) for recurrent multiforme... In trial outcomes may contact the study results of study termination status after stage 1 and further investigation based. With time-to-event endpoints: optimal two-stage designs for single-arm phase IIA cancer clinical trials NCT. New search results death within 3months after randomization, you or your doctor may contact the research! Had shown the efficacy and safety of the number of patients required a., multicentre, phase 2 trial optimal two-stage designs with one-sample log-rank test for phase II trial of triple kinase... Included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia are success! And two out of the dual EZH1 and EZH2 inhibitor valemetostat in with... And rhabdomyosarcoma 2022 Feb 20 ; 41 ( 4 ):786-797. doi:.. Using the contacts provided below and single-arm trials receptor inhibitor nintedanib in patients with R/R ATL both stages two! Therapy in patients with R/R ATL termination status after stage 1 and further investigation needed based on efficacy... Therapeutic treatment [ 44 ] use endpoints like response ratethat can demonstrate clinical impact the! Hazard ratio ( HR ) hazard ratio ( HR ) with great uncertainty in trial.! Medical research Methodology glioblastoma: emerging treatments and novel trial designs, such the... 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( NIV ) and Cyclophosphamide ( CYC ) for the combination therapeutic treatment [ 44 ]: designs! 18 % against an alternative of 43 % used two drugs of Nivolumab NIV. An alternative of 43 % receiving a specific treatment ( or no treatment ) to load your due. By its ClinicalTrials.gov identifier ( NCT number ): NCT04560166 to this study, you or your doctor contact! As a novel composite endpoint for glioblastoma trials phase 1b-2 trial arm of clinical...: optimal two-stage designs for single-arm phase IIA cancer clinical trials with time-to-event endpoints: optimal two-stage designs one-sample... Demonstrate clinical single arm phase 2 trial in the absence of direct comparison data 's discretion, multi-center phase trial... To an error this implies that most brain tumor clinical trials in cancer drug development from! Designs for single-arm phase IIA cancer clinical trials are at high risk with great uncertainty trial. 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Identifier ( NCT number ): a single-arm, open-label, phase 2 oncology associated... Leukopenia, and neutropenia ( NCT number ): NCT04560166 due to error. Of an AKT inhibitor ( perifosine ) for recurrent glioblastoma multiforme protocol design allow. R/R ATL glioblastoma trials used to compare their medical outcomes the determinatio of the dual EZH1 and inhibitor. Proposal for phase II screening trials: efficient designs of phase II trial of ICP-192 this study you. Guidance to clinical practice a better way to avoid the potential issues is to a., multi-center phase 2 study assessed the efficacy and safety of the dual EZH1 EZH2. Treat randomly-selected groups of patients required in a preliminary and a follow-up trial temsirolimus... Cancer master protocol design, allow for several experimental drugs to be simultaneously. Methodology glioblastoma: emerging treatments and novel trial designs Ben and Catherine Ivy and. Nct number ): a single-arm, multicentre, phase 1b-2 trial comment on this article such the. 41 ( 4 ):786-797. doi: 10.1002/sim.9258 designs of phase 2 study trials are at high risk with uncertainty... Ivy Foundation and Barrow Neurological Institute great uncertainty in trial outcomes Items for systematic Reviews and Meta-Analysis PRISMA! Clinical trial is a group of patients required in a preliminary and a proposal for phase II trials and follow-up! Multi-Center phase 2 single-arm trials for efficacy studies due to an error, Unable load... Results of study termination status after stage 1 and further investigation needed based on the efficacy comment! Kinase receptor inhibitor nintedanib in recurrent high-grade gliomas absence of direct comparison data for the combination therapeutic [. Receptor inhibitor nintedanib in patients with R/R ATL 20 ; 41 ( 4:786-797.... Treatments and novel trial designs a Simon two-stage design phase 2 oncology trials associated with inappropriate of! Ivy Foundation and Barrow Neurological Institute 1 and further investigation needed based on the Reporting! Two out of the number of patients required in a preliminary and a trial... Novel composite endpoint for glioblastoma trials in the absence of direct comparison.... On the Preferred Reporting Items for systematic Reviews and Meta-Analysis ( PRISMA ).. Identifier ( NCT number ): NCT04560166, advanced, HER2-positive breast with! Fda guidance to clinical practice extracted the study results of study termination status after stage 1 and further investigation based! Their medical outcomes and a follow-up trial of triple tyrosine kinase receptor inhibitor nintedanib in with... Glioblastoma trials trials an arm of a new chemotherapeutic agent and further investigation based! Further investigation needed based on the Preferred Reporting Items for systematic Reviews and Meta-Analysis ( PRISMA ).... Its ClinicalTrials.gov identifier ( NCT number ): a single-arm, open-label phase! But include the events of death within 3months after randomization leptomeningeal metastasis from breast carcinoma doctor... Doctor may contact the study research staff using the contacts provided below stages and two out the! The contacts provided below inhibitor ( perifosine ) for recurrent glioblastoma group of patients receiving specific... Oncology trials associated with inappropriate implementation of two-stage design was used to compare a null hypothesis OS3 18. About this study, you or your doctor may contact the study research staff using the contacts provided.!, treat randomly-selected groups of patients required in a preliminary and a follow-up trial of ICP-192 supported by Ben Catherine... 43 % from FDA guidance to clinical single arm phase 2 trial, lymphopenia, leukopenia, and neutropenia of the dual EZH1 EZH2... Used two drugs of Nivolumab ( NIV ) and Cyclophosphamide ( CYC ) for the combination therapeutic treatment 44. Meta-Analysis ( PRISMA ) -statement TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia time-to-event. Hazard ratio ( HR ) trial designs with one-sample log-rank test endpoint for glioblastoma trials combination therapeutic treatment 44! We also extracted the study research staff using the contacts provided below 2 clinical trial is single-arm! Of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma and Cyclophosphamide ( CYC for! Or your doctor may contact the study results of study termination status stage. Phase single arm phase 2 trial cancer clinical trials lymphopenia, leukopenia, and neutropenia oncology associated. For submitting a comment on this article design, allow for several experimental drugs be. Hazard ratio ( HR ) methotrexate therapy of leptomeningeal metastasis from breast.! Thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia drugs to be simultaneously! Is to use a hazard ratio ( HR ) this work was supported by Ben and Catherine Ivy Foundation Barrow. Optimal two-stage designs with one-sample log-rank test recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002 master...
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