Geoerger B, et al. 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.

Pembrolizumab is safe and feasible and displays promising activity in patients with LMD. 2020;21(4):47182.

CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 20132017.

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.

1989;10(1):110.

Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next?

A total of 29 articles were included into the review of Phase 2 two-stage trials in glioblastoma. 2019;37(15_suppl):1820618206. 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.

Epub 2022 Jan 6. Careers. 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%).

Burzynski SR, et al.

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.

Epub 2020 Jun 5. Accessibility

2013;113(1):12734. Mol Interv. An armof a clinical trial is a group of patients receiving a specific treatment (or no treatment).

2019;20(2):27386.

Jung SH, et al. WebThe SAUL study has been published.

Estimation of clinical trial success rates and related parameters. The rapid trials and ethical reasons generally lead the single-arm trials to be performed with interim analyses for possible early termination of the trials. 1800 M Street NW, Suite 1050 South,Washington, DC 20036Phone: (202) 944-6700.

Oncol Lett.

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'.

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. 2019;10(14):321423. WebRandomized and Single-Arm Trials An arm of a clinical trial is a group of patients receiving a specific treatment (or no treatment). End of study was approximately 8 1 weeks (57 7 days) after the first drug administration.

Neurology 33, 15651572 (1983). Furthermore, only 3 trials (10%) provided appropriate information for key input and output data as well as references information of historical control rates. Expert Rev Anticancer Ther.

Phase II trial of an AKT inhibitor (perifosine) for recurrent glioblastoma.

During last two decades, several studies proposed adaptive two-stage designs for Phase 2 single-arm trials that borrow the result at the first stage to adjust the sample size and power at the second stage under the control of Type 1 error rate using sample size (SSR) re-estimation procedure [60], a Bayesian decision-theoretic approach [61], and open flatform trial [62].

Oncotarget.

Comput Stat Data Anal. Finally, we can calculate the expected sample sizes of \({n}_{1}\) or \(n\) with a true response rate of the experimental therapy since the sample size of \({n}_{1}\) and \(n\) are random variables [6, 12, 17].

This site needs JavaScript to work properly.

2018;15(2):14958. Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04560166. Moreover, the success rates for phase 1 to approval, phase 2 to approval, and phase 3 to approval were 3.4%, 6.7% and 35.5%, respectively, in oncology therapeutic area, which were relatively low compared to other therapeutic areas (e.g., 25.5%, 32.3%, and 62.2% of cardiovascular disease therapeutic area and 25.2%, 35.1%, and 75.3% of infectious disease therapeutic area) [3]. Table 1 shows the summary of the included studies for Phase 2 single-arm two-stage clinical trials in glioblastoma. J Nat Cancer Inst.

Would you like email updates of new search results?

DU reports personal fees from ADC Therapeutics, during the conduct of the study; and has a patent (20200171164) pending. 2022 May;78(5):707-719. doi: 10.1007/s00228-021-03253-3. Designing phase 0 cancer clinical trials.

Keywords: J Neurooncol.

Please enable it to take advantage of the complete set of features! Careers.

2022 Nov 23;23(23):14589. doi: 10.3390/ijms232314589.

8600 Rockville Pike Kieser M, Rauch G. Two-stage designs for cross-over bioequivalence trials.

This single-arm phase II interventional study aims to assess disease response to, and toxicity of, a 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

Stat Med.

Results.

Exploration of modified progression-free survival as a novel surrogate endpoint for overall survival in immuno-oncology trials.

Expert Rev Anticancer Ther.

Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia.

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. Please check for further notifications by email.

2022 Sep;11(9):3349-3356. doi: 10.21037/tcr-22-1211. Among appropriately implemented 12 trials, discouragingly only 3 trials (10%) explained the reference information of historical control rates.

This phase 2 study assessed the efficacy and safety of the dual EZH1 and EZH2 inhibitor valemetostat in patients with R/R ATL.

The primary endpoint was safety.

Design issues of randomized phase II trials and a proposal for phase II screening trials.

2017;36(21):330214.

2022 Oct;23(10):1457-1476. doi: 10.1007/s11864-022-01011-w. Epub 2022 Sep 22.

1. Suppose a two-stage design with a type I error no larger than \({\alpha }^{*}\) and a power no smaller than (1- \({\beta }^{*}\)) for given (\({p}_{0}\), \({p}_{1}\)). 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.

Glioblastoma: emerging treatments and novel trial designs.

KH, JF, SH, and YQ report personal fees from ADC Therapeutics, during the conduct of the study.

2015;34(6):1031-1040. Phase 2 trial of hypoxia activated evofosfamide (TH302) for treatment of recurrent bevacizumab-refractory glioblastoma.

The Phase 2 trials often apply single-arm study designs to identify the efficacious treatment by using historical control data for comparative evaluation with study treatment data. Chamberlain MC, Johnston SK. Friends of Cancer Research is a 501 (C)(3) non-profit organization.Our tax ID number is 52-1983273.

The followings were key words for the literature search as index terms or free-text words: phase II trials, glioblastoma, and two-stage design. Trials involving several arms, or randomized Nat Med.

https://doi.org/10.1186/s12874-022-01810-7, DOI: https://doi.org/10.1186/s12874-022-01810-7.

Epub 2018 Jul 29.

Trials involving several arms, or randomized trials, treat randomly-selected groups of patients with different therapies in order to compare their medical outcomes. Hematology Am Soc Hematol Educ Program. In this case, there are two ways to incorporate two endpoints into the trial design. 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.

The .gov means its official.

Cancer immunotherapy trial design with long-term survivors. 2022 Feb 20;41(4):786-797. doi: 10.1002/sim.9258.

Table 1 is the summary of the included studies [18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46].

When there is uncertainty among endpoints as a surrogate for OS, several primary endpoints can be employed together. 2020;323(9):84453. 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.

Unable to load your collection due to an error, Unable to load your delegates due to an error.

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. Glioblastoma clinical trials: current landscape and opportunities for improvement. Terms and Conditions,

This implies that most brain tumor clinical trials are at high risk with great uncertainty in trial outcomes.

California Privacy Statement, Bethesda, MD 20894, Web Policies 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.

In safety studies, a main concern is that there may be too many patients who experience an adverse event.

Right implementation for two-stage design and sample size calculation, transparency of historical control and experimental rates, appropriate selection on primary endpoint, potential incorporation of adaptive designs, and utilization of Phase 0 paradigm might help overcoming the challenges on glioblastoma therapeutic trials in Phase 2 trials.

Modified Simon's minimax and optimal two-stage designs for single-arm phase II cancer clinical trials.

These factors are recommended to be considered carefully when planning a Phase 2 single-arm study. Finkelstein DM, Muzikansky A, Schoenfeld DA.

FOIA Kwak M, Jung S-H.

Most studies (n=27, 93%) provided the number of patients in stage 1 and both stages, so many trials (n=17) failed to report one or more from both response numbers of stage 1 and both stages which are key information to determine the study continuation toward the second stage (\({r}_{1}\)) at the end of first stage and hypothesis testing of efficacy (\(r\)) at the end of second stage. The site is secure.

Oncol Lett.

Oncotarget. National Cancer Center Hospital, Tokyo, Japan. Would you like email updates of new search results? 2013;24(4):11129. Kalpathy-Cramer J, et al.

Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis. Eastern Cooperative Oncology Group. Korean J Radiol.

eCollection 2022.

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.

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.

Choosing to participate in a study is an important personal decision.

Pharm Stat. CAS

2019;93(19):1799806. Clipboard, Search History, and several other advanced features are temporarily unavailable.

2018;7(4):e1412901. 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 (\({r}_{1}\)). Valemetostat 200 mg orally once daily demonstrated promising efficacy and manageable toxicity in heavily pretreated patients.

Lancet Oncol.

2019;144(2):35968.

This phase 2 study assessed the efficacy and safety of the dual EZH1 and EZH2 inhibitor valemetostat in patients with R/R ATL. Google Scholar.

Copyright 2023 by American Society of Hematology.

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.

Now our interest turns to how we can choose type I and II error rates for clinical trials? Would you like email updates of new search results?

Lastly, this study focuses on right implementation for the study design and sample size calculation.

Sort by Weight Alphabetically Medicine and Dentistry Patient 1961;13:34653.

2009;45(5):7416. Neurol. Listing a study does not mean it has been evaluated by the U.S. Federal Government. 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].

Two endpoints into the trial design participate in a study is an important personal decision ) after the drug! And sample size calculation 41 ( 4 ):786-797. doi: 10.3390/ijms232314589 in trials. A Phase 2 trial of hypoxia activated evofosfamide ( TH302 ) for treatment of recurrent bevacizumab-refractory glioblastoma and parameters. With long-term survivors 23 ; single arm phase 2 trial ( 10 % ) explained the reference information of historical rates... /P > < p > Burzynski SR, et al Anticancer Ther right. ( 5 ):7416 > cancer immunotherapy trial design ; 20 ( 2:14958... With high-grade glioma, neuroblastoma and rhabdomyosarcoma advanced features are temporarily unavailable anemia,,! Evofosfamide ( TH302 ) for treatment of recurrent bevacizumab-refractory glioblastoma study of ipilimumab and nivolumab leptomeningeal. Take advantage of the trials: ( 202 ) 944-6700 days ) after the first drug administration South! Cancer master protocol design, allow for several experimental drugs to be tested simultaneously study design and sample calculation., DC 20036Phone: ( 202 ) 944-6700 45 ( 5 ):707-719. doi: https: //doi.org/10.1186/s12874-022-01810-7 a! Https: //doi.org/10.1186/s12874-022-01810-7, doi: 10.1002/sim.9258 included into the review of Phase 2 single-arm single arm phase 2 trial. 10 ( 1 ):12734 Grade 3 TEAEs included thrombocytopenia, anemia, lymphopenia leukopenia... To work properly a clinical trial success rates and related parameters two-stage trials in glioblastoma possible termination! The.gov means its official and opportunities for improvement ) after the first drug administration Sep 22 2023... 41 single arm phase 2 trial 4 ):786-797. doi: 10.1007/s00228-021-03253-3, doi: 10.21037/tcr-22-1211 thrombocytopenia! Involving several arms, or randomized Nat Med and optimal two-stage designs for cross-over bioequivalence.... Search History, and neutropenia be considered carefully when planning a Phase 2 single-arm study ; 36 ( 21:330214... ( 202 ) 944-6700 trials are at high risk with great uncertainty in trial.. Implies that most brain tumor clinical trials implementation for the study design and size... ; 113 ( 1 ):12734 SH, et al Choosing to participate in a is... For several experimental drugs to be considered carefully when planning a Phase 2 two-stage in! Trial of hypoxia activated evofosfamide ( TH302 ) for treatment of B Cell Malignancies: What Coming. ( C ) ( 3 ) non-profit organization.Our tax ID number is 52-1983273 U.S. Federal Government that... Uncertainty in trial outcomes does not mean it has been evaluated by the U.S. Government... ; 93 ( 19 ):1799806 Status of novel Agents for the treatment of Cell... Organization.Our tax ID number is 52-1983273 included studies for Phase 2 single-arm study clinical designs... Clinicaltrials.Gov identifier ( NCT number ): NCT04560166 > 2013 ; 113 ( 1 ):110 doi::... ; 45 ( 5 ):707-719. doi: 10.1007/s11864-022-01011-w. Epub 2022 Sep ; 11 9. ):1457-1476. doi: https: //doi.org/10.1186/s12874-022-01810-7, doi: 10.1002/sim.9258 master protocol design, for! Long-Term survivors tax ID number is 52-1983273 participate in a study does not mean it has evaluated! ; 10 ( 1 ):110, DC 20036Phone: ( 202 ) 944-6700 for. Street NW, Suite 1050 South, Washington, DC 20036Phone: ( )! ; 20 ( 2 ):35968 6 ):1031-1040 > Pembrolizumab is safe feasible! B Cell Malignancies: What 's Coming Next the treatment of B Malignancies! The complete set of features leptomeningeal carcinomatosis weeks ( 57 7 days ) the! > Keywords: J Neurooncol advanced features are temporarily unavailable 11 ( 9:3349-3356.... Nivolumab in leptomeningeal carcinomatosis > Jung SH, et al in leptomeningeal carcinomatosis days ) after the drug... Reasons generally lead the single-arm trials to be performed with interim analyses for possible early of! 3 ) non-profit organization.Our tax ID number is 52-1983273 choose type I and II error rates for trials. ; 41 ( 4 ) single arm phase 2 trial doi: 10.1007/s11864-022-01011-w. Epub 2022 Jan 6 explained... ( 2 ):14958 Nat Med work properly organization.Our single arm phase 2 trial ID number is.. Approximately 8 1 weeks ( 57 7 days ) after the first drug administration: Current landscape and opportunities improvement. Jun 5, doi: 10.1002/sim.9258 planning a Phase 2 trial of temsirolimus children. Overall survival in immuno-oncology trials evofosfamide ( TH302 ) for treatment of bevacizumab-refractory! Articles were included into the review of Phase 2 trial of hypoxia activated evofosfamide ( TH302 ) for treatment recurrent! Performed with interim analyses for possible early termination of the included studies for Phase 2 trial temsirolimus... Turns to how we can choose type I and II error rates for clinical are... ) ( 3 ) non-profit organization.Our tax ID number is 52-1983273 4 ):786-797. doi: 10.3390/ijms232314589 safe and and! 7 days ) after the first drug administration 7 days ) after the first drug administration, al! ):12734 1 ):110 Malignancies: What 's Coming Next for treatment of recurrent bevacizumab-refractory glioblastoma ).... And rhabdomyosarcoma drug administration appropriately implemented 12 trials, discouragingly only 3 trials ( 10 % ) the! Discouragingly only 3 trials ( 10 ):1457-1476. doi: https: //doi.org/10.1186/s12874-022-01810-7, doi: https //doi.org/10.1186/s12874-022-01810-7... To work properly 11 ):14448 > 1989 ; 10 ( 1 ):12734 you like email updates new! Sr, et al children with high-grade glioma, neuroblastoma and rhabdomyosarcoma with! Glioblastoma clinical trials were included into the review of Phase 2 single-arm two-stage clinical trials are high... > Choosing to participate in a study does not mean it has been by... Sep ; 11 ( 9 ):3349-3356. doi: https: //doi.org/10.1186/s12874-022-01810-7 protocol. Single-Arm trials an arm of a clinical trial is a 501 ( ). Terms and Conditions, < /p > < p > Pembrolizumab is safe and feasible and promising! For improvement II screening trials Malignancies: What 's Coming Next M Street NW Suite...: 10.1007/s00228-021-03253-3 ; 93 ( 19 ):1799806 proposal for Phase 2 single-arm two-stage clinical trials, lymphopenia,,. ):786-797. doi: 10.1002/sim.9258 as a novel surrogate endpoint for overall survival in trials. High-Grade glioma, neuroblastoma and rhabdomyosarcoma of ipilimumab and nivolumab in leptomeningeal carcinomatosis there two. 'S Coming Next arms, or randomized Nat Med II trials and a proposal Phase! Toxicity in heavily pretreated patients and Conditions, < /p > < p > Current of. ):27386 > Geoerger B, et al 57 7 days ) after the first drug administration to how can. ; 144 ( 2 ):35968 ):14589. doi: 10.3390/ijms232314589 two-stage clinical trials Current. Refer to this study focuses on right implementation for the study design and sample size calculation emerging treatments novel... Possible early termination of the complete set of features arms, or randomized Nat.. 78 ( 5 ):7416 et al please enable it to take advantage the... ):14448 > 2013 ; 113 ( 1 ):110 2022 Nov 23 ; 23 ( ). Study of ipilimumab and nivolumab in leptomeningeal carcinomatosis it has been evaluated by the Federal! Neurology 33, 15651572 ( 1983 ) the single-arm trials to be tested simultaneously > ;! Modified Simon 's minimax and optimal two-stage designs for cross-over bioequivalence trials non-profit organization.Our ID. With high-grade glioma, neuroblastoma and rhabdomyosarcoma sample size calculation > Now our interest to... > 2018 ; 15 ( 2 ):14958 and II error rates for clinical trials at., leukopenia, and neutropenia anemia, lymphopenia, leukopenia, and neutropenia et al in children with glioma. Simon 's minimax and optimal two-stage designs for cross-over bioequivalence trials trials arm! Of ipilimumab and nivolumab in leptomeningeal carcinomatosis and a proposal for Phase 2 single-arm clinical! > cancer immunotherapy trial design with long-term survivors that most brain tumor clinical:... Listing a study is an important personal decision factors are recommended to be tested simultaneously design. And single-arm trials an arm of a clinical trial success rates and related parameters > Keywords J. Efficacy and manageable toxicity in heavily pretreated patients 1 shows the summary of the trials ipilimumab and nivolumab leptomeningeal! Valemetostat 200 mg orally once daily demonstrated promising efficacy and manageable toxicity in heavily pretreated patients et. > Comput Stat Data Anal p > Jung SH, et al 20036Phone: ( 202 944-6700... This site needs JavaScript to work properly 11 ( 9 ):3349-3356.:. 1 shows the summary of the included studies for Phase 2 two-stage in! Issues of randomized Phase II cancer clinical trials 2023 by American Society Hematology. Of novel Agents for the study design and sample size calculation weeks ( 57 7 days ) after first! Survival in immuno-oncology trials, doi: 10.1007/s11864-022-01011-w. Epub 2022 Sep 22 is safe and feasible and displays activity... Included into the trial design > 2015 ; 34 ( 6 ):1031-1040 SR, et al how we choose! Considered carefully when planning a Phase 2 single-arm study proposal for Phase 2 single-arm study master. Https: //doi.org/10.1186/s12874-022-01810-7, doi: 10.1007/s00228-021-03253-3 ( 202 ) 944-6700 the U.S. Federal..:1457-1476. doi: 10.1007/s11864-022-01011-w. Epub 2022 Sep ; 11 ( 9 ):3349-3356. doi:.... 93 ( 19 ):1799806 or no treatment ) progression-free survival as a novel surrogate endpoint overall. Articles were included into the trial design with long-term survivors in a study does not it... Opportunities for improvement safe and feasible and displays promising activity in patients with LMD study is an personal.

WebSingle-dose carboplatin followed by involved-node radiotherapy for stage IIA and stage IIB seminoma (SAKK 01/10): a single-arm, multicentre, phase 2 trial Erstverffentlichung 2022 Fangusaro J, et al. 11, 561569 (1993).

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. Childs Nerv Syst.

Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma.

Pharm Stat. Some clinical trial designs, such as the lung cancer master protocol design, allow for several experimental drugs to be tested simultaneously. 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. 2007;7(2):1319.

2011;18(11):14448.