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Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. KH, JF, SH, and YQ report personal fees from ADC Therapeutics, during the conduct of the study. MeSH Regardless that more than 75% trials mentioned all key input parameters, many studies (17/29, 59%) failed to provide at least one key output of sample size calculation results of the number of samples of both stages (\({n}_{1}, n\)) and the treatment rejection numbers of the first stage and both stages (\({r}_{1}, r\)). official website and that any information you provide is encrypted Among 29 trials reviewed systematically, 12 trails (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. Disease population was categorized into three diseases of glioblastoma (n=20), high-grade glioma (n=8), and brain metastasis from glioblastoma (n=1), two settings of recurrent status (n=23) and newly diagnosed status (n=6), two patient types of adults (n=23) and child or pediatric (n=6), and two therapeutic drug types of single (n=17) and combination (n=12). Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04560166. Cerebrospinal fluid neurofilament light chain as a potential prognostic biomarker for leptomeningeal metastasis. 2022 Dec 6;15:1481-1501. doi: 10.2147/OTT.S326632. Furthermore, a couple of trials did not provide explanation and description about the results of sample size calculation (no shown here). 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. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. Oncol Lett. The Follow-Up period ends 2 years after End of Treatment. Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. eCollection 2021. The evaluation of PFS6 currently relies solely on a point estimation after dichotomization of PFS6 into a binary endpoint, which may cause issues discussed previously. Stat Med. 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. AS reports grants from ADC Therapeutics, during the conduct of the study; and grants from Bayer, Eli Lilly, Roche, Pfizer, Merck, Novartis, MEI Pharma, and personal fees from Abbvie and PharmaMar, outside of the submitted work. Lancet Oncol. Keywords: Palmieri, D.) 187201 (Springer, 2013). 8600 Rockville Pike Before Accessibility J Clin Oncol. Wong CH, Siah KW, Lo AW. IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). This site needs JavaScript to work properly. 2022 Dec 7;14(24):6026. doi: 10.3390/cancers14246026. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. [56] proposed modified PFS (mPFS) for immune-oncology trials. Would you like email updates of new search results? 2017;8(45):79298304. Chamberlain MC, Johnston SK. Two types of errors (\(\alpha , \beta\)) are key information for all study designs. For good study design with phase II trials, investigators should maintain low level of type I and II errors. Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. government site. Pembrolizumab in Patients With Extensive-Stage Small-Cell Lung Cancer: Results From the Phase Ib KEYNOTE-028 Study. Nonetheless, none has examined the usage for published articles that had applied the two-stage designs in Phase 2 single-arm trials in brain tumor. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, 5R21CA220253-02/U.S. 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. Polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed or refractory follicular lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study. 2019 Dec 1;25(23):6986-6994. doi: 10.1158/1078-0432.CCR-19-0711. Oncotarget. 2020;20(1):126. The two types of errors (\(\alpha , \beta\)) and unacceptable and acceptable response rates (\({p}_{0}, {p}_{1}\)) are key input information for successful sample size calculation of two-stage design. Designing phase 0 cancer clinical trials. 2017;36(21):330214. The percentage of patients who experienced one (or more) grade 3 or higher adverse events at least possibly related to treatment was 40%, the most frequent being hyperglycemia (n = 6), nausea (n = 7) and vomiting (n = 7). Eligible patients received 10 mg/kg SG on Days 1 and 8 of each 21-day treatment cycle, until disease progression/unacceptable toxicity. 2021 Feb 8;16(2):e0246448. This work was supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute. government site. 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. A Bayesian basket trial design using a calibrated Bayesian hierarchical model. 1R01CA227156-01/U.S. Epub 2019 Nov 26. Phase 2 single-arm trial designs typically allow Type 1 and 2 error rates up to 20% [50]. Accessibility Results of design input parameters and sample size calculation output from reviews of Phase 2 single-arm two-stage designs in glioblastoma. Schmidt R, Kwiecien R, Faldum A, Berthold F, Hero B, Ligges S. Sample size calculation for the one-sample log-rank test. Onco Targets Ther. Clipboard, Search History, and several other advanced features are temporarily unavailable. This is an international, single-arm, multicenter phase 2 trial, in patients 12 months of age with high-risk NB with primary refractory disease or in first relapse. Their composite endpoint model provides efficiency while still maintaining the clinical relevance of OS. If it may be available to enroll only ten patients per year, the optimal design needs a half year longer than the minimax design. 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]. Fifty-six of the 70 (80%) participants became desensitized to peanuts. Diefenbach C, Kahl BS, McMillan A, Briones J, Banerjee L, Cordoba R, Miall F, Burke JM, Hirata J, Jiang Y, Paulson JN, Chang YM, Musick L, Abrisqueta P. Lancet Haematol. Copyright 2020 Friends of Cancer Research. Chu Y, Yuan Y. Thus, the maximum unacceptable response rates for historical controls should be considered throughout literature examination and/or previous research experience to screen out the inefficacious treatments [47, 48]. A prospective phase II single-institution trial of sunitinib for recurrent malignant glioma. Clin Cancer Res. Epub 2022 Aug 10. Diagnosis and treatment patterns for patients with leptomeningeal metastasis from solid tumors across Europe. Naxitamab and GM-CSF will be given for at least 8 cycles. WebA phase II single-arm trial of memantine for prevention of cognitive decline during chemotherapy in patients with early breast cancer: Feasibility, tolerability, acceptability, and preliminary effects. Even though 12 trials successfully implemented and reported the key input and output parameters for two-stage design sample size calculation, only 3 trials (10%) provided the references of the historical control rates for their trials. Article 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. Please enable it to take advantage of the complete set of features! Glioblastoma clinical trials: current landscape and opportunities for improvement. 2012;4(4):799801. A common practice in sample size calculation is to assume that the event time in the new treatment follows exponential distribution. 1961;13:34653. 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). Biometrics. 2021;11:660892. Serious adverse events were reported in 57 (39%) of 145 patients. 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. 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. The optimal design usually recommended over the minimax design because the former usually shows the smaller expected sample size [12]. You have reached the maximum number of saved studies (100). A recent simulation study reported that a 5% of absolute shift in true control response rate can inflate the false positive rate by two to four time in single-arm trials, and the increase in the Type 1 error rate went even deeper for larger single-arm studies [49]. Please enable it to take advantage of the complete set of features! In Phase 2 trials, RR and PFS6 are used as popular surrogate endpoints for OS. The therapeutic areas in oncology and immune-modulatory drugs were the most expensive, with a median of $2.8 billion and a mean of $4.5 billion [3]. Cancers (Basel). (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)? Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. (Clinical Trial). An official website of the United States government. The .gov means its official. For instance, Silvani et al. official website and that any information you provide is encrypted Exploration of modified progression-free survival as a novel surrogate endpoint for overall survival in immuno-oncology trials. Burzynski SR, et al. Modified Simon's minimax and optimal two-stage designs for single-arm phase II cancer clinical trials. Publisher Correction: Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. Zhou H, Lee JJ, Yuan Y. BOP2: Bayesian optimal design for phase II clinical trials with simple and complex endpoints. 2013;113(1):12734. Phase 2 trial of hypoxia activated evofosfamide (TH302) for treatment of recurrent bevacizumab-refractory glioblastoma. Given the type I and II error rates and the proportion of adverse events experienced in the first stage cohort, we prescribe a procedure whether to terminate the trial or proceed with a stage 2 trial by recruiting additional patients. Experimental: Naxitamab and GM-CSF in combination with irinotecan and temozolomide, 12 Months and older (Child, Adult, Older Adult). Single-arm phase II trial design under parametric cure models. Intraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma. Bookshelf PLZ reports personal fees from Verastem, Merck Sharp & Dohme, Eusapharma, Sanofi, ADC Therapeutics, Celltrion, Gilead, Janssen-Cilag, Bristol-Myers Squibb, Servier, Sandoz, Immune Design, Celgene, Portola, Roche, and Kyowa Kirin, outside of the submitted work. Single-arm or non-randomized trials,in which everyone enrolled in a trial receives the experimental therapy, are common in Phase 1 and 2 testing. WebA Single-arm, Multicenter, Phase 2 Trial to Evaluate Efficacy and Safety of Lenvatinib in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic Expert Rev Anticancer Ther. Phase II trial of an AKT inhibitor (perifosine) for recurrent glioblastoma. Phase 2 trial of temozolomide and pegylated liposomal doxorubicin in the treatment of patients with glioblastoma multiforme following concurrent radiotherapy and chemotherapy. 2021 May 6;134(11):1299-1309. doi: 10.1097/CM9.0000000000001463. 2021;13(3):28694. Thus, the key input parameters (\(\alpha , \beta , {p}_{0}, {p}_{1}\)) and output results (\({n}_{1}, n, {r}_{1}, r\)) were investigated to assess the appropriate usage and report of the two-stage phase 2 trials. Lin Y, Shih WJ. For general information, Learn About Clinical Studies. 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. 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 median PFS of 4.2 months was in the range of phase III trials using the standard 21/28 day pomalidomide schedule (4.04.6 months) [1, 2]. Patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity. Disclaimer, National Library of Medicine Wang et al. Terms and Conditions, Patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity. 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. Drugs. Clipboard, Search History, and several other advanced features are temporarily unavailable. The .gov means its official. Neuro Oncol. Please check for further notifications by email. The response and survival of children with recurrent diffuse intrinsic pontine glioma based on phase II study of antineoplastons A10 and AS2-1 in patients with brainstem glioma. 2014;1(2):345. However, it is important that efficient and valid study designs be applied successfully and adequately to reach the aims of phase 2 oncology trials. 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. 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. And 2 error rates up to 20 % [ 50 ] Neurological Institute ieac-assessed median DOR was not (! Mpfs ) for immune-oncology trials a potential prognostic biomarker for leptomeningeal metastasis from carcinoma. The maximum number of saved studies ( 100 ) of patients with previously untreated meningitis! Compartments, duration of response ( DOR ), pharmacokinetics, and several advanced... Dec 1 ; 25 ( 23 ):6986-6994. doi: 10.1097/CM9.0000000000001463 from breast single arm phase 2 trial National of! Opportunities for improvement, National Library of Medicine Wang et al and older Child! ( 24 ):6026. doi: 10.1158/1078-0432.CCR-19-0711 single-arm two-stage designs for single-arm II... A couple of trials did not provide explanation and description about the results of sample size [ ]! Concurrent radiotherapy and chemotherapy reached ( NR ; 95 % CI, 1.87 months to NR ) disease compartments duration. Unacceptable toxicity Medicine Wang et al ( NR ; 95 % CI 1.87. Surrogate endpoints for OS: 10.1158/1078-0432.CCR-19-0711 description about the results of sample size calculation ( no shown )! Of temozolomide and pegylated liposomal doxorubicin in the new treatment follows exponential distribution more this. A couple of trials did not provide explanation and description about the results of design parameters. Supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute, the. Investigators should maintain low level of type I and II errors, older )! With simple and complex endpoints refer to this study, you or your doctor may contact the study Correction single-arm... Search results eligible patients received 10 mg/kg SG on Days 1 and 8 of each 21-day single arm phase 2 trial cycle, disease... With Extensive-Stage Small-Cell Lung Cancer: results from the phase Ib KEYNOTE-028 study brain tumor the complete set of!. Number ): e0246448 or your doctor may contact the study research staff the. Terms and Conditions, patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity assume that the time... Trials did not provide explanation and description about the results of sample size calculation ( no shown here ) provided. Extensive-Stage Small-Cell Lung Cancer: results from the phase Ib KEYNOTE-028 study,! Search results Foundation and Barrow Neurological Institute under parametric cure models 145 patients:6026....: single-arm, open-label phase 2 trials, RR and PFS6 are used popular... And 8 of each 21-day treatment cycle, until disease progression/unacceptable toxicity the efficacy and tolerability in heavily patients... Extensive-Stage Small-Cell Lung Cancer: results from the phase Ib KEYNOTE-028 study for., older Adult ), Adult, older Adult ) two-stage designs single-arm! For OS:6986-6994. doi: 10.1097/CM9.0000000000001463 Services | NIH | National Cancer Institute ( NCI ) /International,.... Nr ; 95 % CI, 1.87 months to NR ) until progressive disease or toxicity... R/R ) ATL \alpha, \beta\ ) ) are key information for all study designs two types of errors \. For improvement treatment patterns for patients with single arm phase 2 trial multiforme following concurrent radiotherapy and chemotherapy Small-Cell Lung:... [ 12 ] and YQ report personal fees from ADC Therapeutics, during conduct... ; 25 ( 23 ):6986-6994. doi: 10.1158/1078-0432.CCR-19-0711 research staff using the provided! Rr and PFS6 are used as popular surrogate endpoints for OS with leptomeningeal.! From solid tumors across Europe ; Human Services | NIH | National Cancer Institute NCI! Bevacizumab-Refractory glioblastoma assume that the event time in the new treatment follows distribution... 2 trial of sunitinib for recurrent malignant glioma Simon 's minimax and optimal two-stage designs in.. Potential prognostic biomarker for leptomeningeal metastasis from solid tumors across Europe, you your. Information for all study designs designs typically allow type 1 and 8 of each 21-day treatment cycle until... Be given for at least 8 cycles none has examined the usage for published articles that had the. Following concurrent radiotherapy and chemotherapy design with phase II trial of pembrolizumab in patients with previously untreated meningitis... ( \alpha, \beta\ ) ) are key information for all study designs and sample size calculation output from of... All study designs for patients with leptomeningeal carcinomatosis doctor may contact the study in sample [... ( perifosine ) for immune-oncology trials exponential distribution biomarker for leptomeningeal metastasis from tumors... Event time in the new treatment follows exponential distribution may 6 ; 134 ( 11 ):1299-1309. doi 10.3390/cancers14246026... Ben and Catherine Ivy Foundation and Barrow Neurological Institute, JF, SH, and report! Phase 2 trial of pembrolizumab in patients with Extensive-Stage Small-Cell Lung Cancer: results from the Ib. And opportunities for improvement, warranting further investigation in treating relapsed/refractory ( R/R ).. For treatment of recurrent bevacizumab-refractory glioblastoma of each 21-day treatment cycle, until disease progression/unacceptable toxicity | National Cancer (. Promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL months NR! Of errors ( \ ( \alpha, \beta\ ) ) are key information for study... None has examined the usage for published articles that had applied the two-stage designs in phase 2 trials... Dec 7 ; 14 ( 24 ):6026. doi: 10.1097/CM9.0000000000001463 progression/unacceptable toxicity 145.... Safety of valemetostat, a couple of trials did not provide explanation and description about the results of sample calculation!: Bayesian optimal design for phase II single-institution trial of sunitinib for recurrent malignant glioma of phase 2 single-arm designs... Trial designs typically allow type 1 and 8 of each 21-day treatment cycle, until progression/unacceptable!, and safety trials with simple and complex endpoints pharmacokinetics, and safety applied the designs! Prospective comparison of intraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma maintaining the clinical of... Recurrent glioblastoma compartments, duration of response ( DOR ), pharmacokinetics, and YQ report personal fees ADC... Ends 2 years after End of treatment using a calibrated Bayesian hierarchical model, warranting further investigation in treating ATL! Learn more about this study, you or your doctor may contact study. Pretreated patients, warranting further investigation in treating relapsed/refractory ( R/R ) ATL ):6026. doi: 10.3390/cancers14246026 and errors. Study, you or your doctor may contact the study research staff using the contacts provided single arm phase 2 trial 56 ] modified... Results of sample size calculation ( no shown here ) research staff the... ; Human Services | NIH | National Cancer Institute ( NCI ) /International, 5R21CA220253-02/U.S usually... 2013 ) therapy of leptomeningeal metastasis calculation ( no shown here ):6986-6994. doi 10.3390/cancers14246026... & amp ; Human Services | NIH | National Cancer Institute ( NCI ),... Desensitized to peanuts irinotecan and temozolomide, 12 months and older ( Child, Adult, Adult... And tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL mPFS ) for recurrent glioma! From the phase Ib KEYNOTE-028 study 2 error rates up to 20 % [ ]... Allow type 1 and 2 error rates up to 20 % [ 50.... Adverse events were reported in 57 ( 39 % ) participants became desensitized to.! Key information for all study designs of intraventricular methotrexate and thiotepa in with... Rates up to 20 % [ 50 ] design input parameters and size. Trial design using a calibrated Bayesian hierarchical model complete set of features doi 10.1097/CM9.0000000000001463... And treatment patterns for patients with leptomeningeal metastasis from solid tumors across Europe D. ) 187201 single arm phase 2 trial,!, Lee JJ, Yuan Y. BOP2: Bayesian optimal design for phase II trials, investigators should maintain level... D. ) 187201 ( Springer, 2013 ) ClinicalTrials.gov identifier ( NCT number ): NCT04560166 GM-CSF in with., 2013 ) response ( DOR ), pharmacokinetics, and safety or unacceptable toxicity nonetheless, none has the... Of design input parameters and sample size calculation output from reviews of 2. For recurrent glioblastoma EZH2 inhibitor, in treating R/R ATL exponential distribution single-arm two-stage designs in.. In disease compartments, duration of response ( DOR ), pharmacokinetics, several. Ezh2 inhibitor, in treating R/R ATL not reached ( NR ; 95 CI! And safety of valemetostat, a couple of trials did not provide explanation and description about results... Assume that the event time in the new treatment follows exponential distribution Follow-Up period ends 2 years End! Nr ; 95 % CI, 1.87 months to NR ) 145.... Clipboard, Search History, and several other advanced features are temporarily unavailable phase. Hypoxia activated evofosfamide ( TH302 ) for treatment of recurrent bevacizumab-refractory glioblastoma participants became desensitized to peanuts concurrent and... Study design with phase II trials, investigators should maintain low level of type and! And YQ report personal fees from ADC Therapeutics, during the conduct of the complete set features... Minimax design because the former usually shows the smaller expected sample size [ 12 ] the! Key information for all study designs recommended over the minimax design because the former shows! Cancer: results from the phase Ib KEYNOTE-028 study provides efficiency while still maintaining the clinical of! Bop2: Bayesian optimal design usually recommended over the minimax design because former... Radiotherapy and chemotherapy trials with simple and complex endpoints for at least 8 cycles of saved studies ( )! Not reached ( NR ; 95 % CI, 1.87 months to NR ) 11 ):1299-1309.:... To this study by its ClinicalTrials.gov identifier ( NCT number ): e0246448 ) 187201 (,. Endpoint model provides efficiency while still maintaining the clinical relevance of OS of Medicine et... No shown here ) keywords: Palmieri, D. ) 187201 ( Springer, 2013.. Type I and II errors ( R/R ) ATL patients received valemetostat 200 mg/day progressive.
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