single arm phase 2 trial

Kummar S, et al. By doing so, the chance to capture the effectiveness of a treatment can be increased. 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. Why Should I Register and Submit Results? Murgo AJ, et al. Please check for further notifications by email. MeSH Wong CH, Siah KW, Lo AW. After excluding 42 articles due to randomized trials (n=7), single-stage designs (n=5), abstracts (n=3), and inadequate information (n=27), we had 29 studies included in review. J. Neurooncol. Careers. 2022 May;9(5):e327-e339. In safety studies, a main concern is that there may be too many patients who experience an adverse event. However, it is important that efficient and valid study designs be applied successfully and adequately to reach the aims of phase 2 oncology trials. Provided by the Springer Nature SharedIt content-sharing initiative. Phase 0 clinical trials in oncology new drug development. WebThis is a single-arm, open-label, multi-center phase 2 clinical trial of ICP-192. Stat Med. sharing sensitive information, make sure youre on a federal This work was supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute. 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. A total of 17 drugs were used as single therapeutic treatment with Sunitinib (SNT) and Nintedanib (NIN) from two studies each, and Temozolomide (TMZ), Bendamustine (BEN), Temsirolimus (TMS), Gimatecan (GMT), Bosutinib (BOS), Dasatinib (DAS), Tivozanib (TIV), Imipridone (IMI), Ortatzxel (ORT), Dovitinib (DOV), Perifosine (PRF), Thrombopoietin receptor (THR), and Pomalidomide (POM) from single study each. As output results, the two-stage designs (Optimal, Minimax, and Admissible designs) produce following key outputs of the number of patients (\({n}_{1}\) and \({n}_{2}\)) for stage 1 and both stages and the rejection numbers (r and \({r}_{1}\)) for both stage 1 and both stages respectively. Optimized image-based surrogate endpoints in targeted therapies for glioblastoma: a systematic review and meta-analysis of phase iii randomized controlled trials. The purpose of this study is to evaluate the efficacy and safety in patients with FGFR2-Rearranged unresectable or metastatic intrahepatic cholangiocarcinoma who failed prior therapy Arms and Interventions Arm: Experimental Drug ICP-192 Outcome Measures Hematology Am Soc Hematol Educ Program. 2013 May;139(1):13-22. doi: 10.1007/s10549-013-2525-y. Fleming TR. The two-stage design tests efficacy using the number of responses at the end of first stage of the trial and only if an efficacy threshold is met can the trial proceed to the second stage. Intrathecal administration of trastuzumab for the treatment of meningeal carcinomatosis in HER2-positive metastatic breast cancer: a systematic review and pooled analysis. 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. Sanai N. Phase 0 clinical trial strategies for the neurosurgical oncologist. Privacy Most trials (n=22, 76%) successfully provided all key information while 7 trials (24%) failed to provide at least one key information (Six trials failed to provide two types of error rates, four trials failed to provide two response rates, and three trials failed to provide two or more than two key results from the sample size calculation). 2020;21(4):47182. Modified Simon's minimax and optimal two-stage designs for single-arm phase II cancer clinical trials. Optimal two-stage designs for exploratory basket trials. 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. [56] proposed modified PFS (mPFS) for immune-oncology trials. 1800 M Street NW, Suite 1050 South,Washington, DC 20036Phone: (202) 944-6700. Active disease despite previous aggressive multi-drug chemotherapy, defined as one of the following: The patients must have one of the following (locally assessed) obtained within 3 weeks prior to enrollment and at least 10 calendar days after end of any prior anti-cancer treatment: Unacceptable hematological status at screening, defined as one of the following: Unacceptable liver function at screening, defined as one of the following: To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. 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. Neurol. MeSH A phase II single-arm study of irinotecan in combination with temozolomide (TEMIRI) in children with newly diagnosed high grade glioma: a joint ITCC and SIOPE-brain tumour study. A common practice in sample size calculation is An International, Single-Arm, Multicenter Phase 2 Trial. 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. Epub 2020 Jun 5. For instance, in Case 3, the 10% and 50% reductions of p0 are 0.45 (=0.50.9) and 0.25 (=0.50.5). Wouters OJ, McKee M, Luyten J. Patients received 200 mg of pembrolizumab intravenously every 3 weeks until definitive progression or unacceptable toxicity. 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. CNS Drugs. Childs Nerv Syst. 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. Epub 2022 Aug 10. 2015;121(3):55763. We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 BMC Med Res Methodol. Wu J, Pan H, Hsu CW. Pharm Stat. Bookshelf 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. HHS Vulnerability Disclosure, Help 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]. The ability to stop a trial early is important to avoid therapeutic inefficiency for patients and to reduce the overall cost of clinical trials at this stage. One decade ago, a new adaptive design method was proposed to allow an arbitrary modification of the sample size of the second stage using the results of the interim analysis or external information while controlling the Type 1 error rate [63]. 2022;169:107420. Admissible two-stage designs for phase II cancer clinical trials. Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. Stat Med. Brastianos, P.K., Brastianos, H. & Eichler, A.F. Diagnosis and treatment patterns for patients with leptomeningeal metastasis from solid tumors across Europe. Would you like email updates of new search results? Epub 2016 Sep 30. 2005;23(28):7199206. Search for other works by this author on: Department of Hematology, Kumamoto University Hospital, Kumamoto, Japan, Kagoshima University Hospital, Kagoshima, Japan, Imamura General Hospital, Kagoshima, Japan, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, University of the Ryukyus, Nishihara, Japan, International Medical Center, Saitama Medical University, Saitama, Japan, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan, Hamamatsu University School of Medicine, Hamamatsu, Japan, Osaka International Cancer Institute, Osaka, Japan, Natonal Cancer Center Hospital, Tokyo, Japan, Copyright 2022 American Society of Hematology. Bethesda, MD 20894, Web Policies Before Copyright 2023 by American Society of Hematology. Norden AD, et al. Vanderbeek AM, et al. 14. Zhou H, et al. Hu J, et al. FOIA Except for three clinical trials that didnt provide the methods used, almost all articles were Simons two-stage designs (n=23, 90%). FOIA government site. Burzynski SR, et al. Wouters and colleagues reported that U. S. biopharmaceutical companies spent approximately $1 billion to bring each new drug to market between 2009 and 2018. This site needs JavaScript to work properly. Clipboard, Search History, and several other advanced features are temporarily unavailable. statement and Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma. 2023 Jan;37(1):45-67. doi: 10.1007/s40263-022-00975-5. 2011;103(3):491501. Oncol. Lastly, this study focuses on right implementation for the study design and sample size calculation. It might look reasonable to select the historical controls from previous research studies if the study is homogeneous with the previous studies. WebA Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants with Previously Treated Glioblastoma or Other Primary Central Nervous System Tumors Harboring Activating FGFR1-3 Alterations (FIGHT-209) Cancer Answer Line 866.223.8100 IRB Study Number 22-1031 Status Recruiting 2023 BioMed Central Ltd unless otherwise stated. Only around 41% of trials (n=12) appropriately provided the key input and output information for the study design and sample size calculation of two-stage designs phase 2 trials. Disclaimer, National Library of Medicine WebIn the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. Disclaimer, National Library of Medicine Altwairgi AK, et al. Drugs. Adult T-cell leukemia/lymphoma (ATL) is an aggressive non-Hodgkin lymphoma with poor prognosis and few treatment options for patients with relapsed, recurrent, or refractory disease. 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 The followings were key words for the literature search as index terms or free-text words: phase II trials, glioblastoma, and two-stage design. OPTIM-ARTSAn adaptive phase II open platform trial design with application to a metastatic melanoma study. Please enable it to take advantage of the complete set of features! Epub 2018 Jul 29. The other three trials used two-stage designs like Inadmissible design, Fleming and Gehan designs. Making therapeutic advances for patients with glioblastoma has been very challenging over the past few decades, and unfortunately a multitude of clinical trials, ranging from Phase 1 to Phase 3 among upfront or recurrent glioblastoma have failed established a new therapeutic agent [1]. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. Englert S, Kieser M. Adaptive designs for single-arm phase II trials in oncology. 2020;20(1):126. Geoerger B, et al. 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 remove one or more studies before adding more. Recent research reported that the success rate in proceeding from Phase 2 to Phase 3 was the lowest among all three rates of Phase 1 to 2, Phase 2 to 3, and Phase 3 to approval (e.g., 29.7%, 20.3%, and 35.5% for oncology and 35.2%, 27.4%, 59% for overall) [2]. Please enable it to take advantage of the complete set of features! Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. Clipboard, Search History, and several other advanced features are temporarily unavailable. Epub 2022 Apr 1. A Simon two-stage design was used to compare a null hypothesis OS3 of 18% against an alternative of 43%. Clin Cancer Res. (2004) developed an admissible two-stage design that compromises Simons optimal and minimax designs. [37] used Simons two-stage optimal design to evaluate the target PFS6 of 35% against the null PFS6 of 20% to achieve 90% power at a 1-sided 10% level, resulting in the required sample size of 58 patients. Phase II study of sunitinib malate in patients with recurrent high-grade glioma. Refining Therapy in Patients with HER2-Positive Breast Cancer with Central Nervous System Metastasis. Sharma M, et al. Phase II study of tivozanib, an oral VEGFR inhibitor, in patients with recurrent glioblastoma. Lassman AB, et al. IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase II multicenter clinical trial. Ananda S, et al. 2021 Dec;8(12):e891-e901. 2021;11:660892. Combining progression-free survival and overall survival as a novel composite endpoint for glioblastoma trials. 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 eCollection 2023 Feb. Tannoury M, Garnier D, Susin SA, Bauvois B. 2019;8(13):598894. Comput Stat Data Anal. WebThe trial ended after accrual completion; the database lock was Dec 31, 2019. Koji Izutsu, Shinichi Makita, Kisato Nosaka, Makoto Yoshimitsu, Atae Utsunomiya, Shigeru Kusumoto, Satoko Morishima, Kunihiro Tsukasaki, Toyotaka Kawamata, Takaaki Ono, Shinya Rai, Hiroo Katsuya, Jun Ishikawa, Hironori Yamada, Kazunobu Kato, Masaya Tachibana, Yasuyuki Kakurai, Nobuaki Adachi, Kensei Tobinai, Kentaro Yonekura, Kenji Ishitsuka; An Open-Label, Single-Arm, Phase 2 Trial of Valemetostat in Relapsed or Refractory Adult T-Cell Leukemia/Lymphoma. Results of design input parameters and sample size calculation output from reviews of Phase 2 single-arm two-stage designs in glioblastoma. Eur J Cancer. 2015;34(6):1031-1040. Phase 2 trial of dasatinib in target-selected patients with recurrent glioblastoma (RTOG 0627). Safety and efficacy of decitabine in combination with temozolomide in metastatic melanoma: a phase I/II study and pharmacokinetic analysis. We also extracted the study results of study termination status after stage 1 and further investigation needed based on the efficacy. 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. 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. The site is secure. Simon's two-stage designs are frequently used in phase II single-arm trials for efficacy studies. Please enable it to take advantage of the complete set of features! A phase 2 study of the first imipridone ONC201, a selective DRD2 antagonist for oncology, administered every three weeks in recurrent glioblastoma. 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. Stat Med. 2016;43(1):138. 2019;85:105807. Another option of two-stage designs is admissible design or spatial design, which came from an idea Can we find a good alternative design between the minimax and optimal design. eCollection 2022. Copyright 2021 Elsevier Ltd. All rights reserved. PLoS One. Ostrom QT, et al. 8600 Rockville Pike 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]. Phase 0 clinical trials in cancer drug development: from FDA guidance to clinical practice. 2009;27(19):30736. The .gov means its official. Estimation of clinical trial success rates and related parameters. eCollection 2022. Neuro Oncol. Glioblastoma (GBM) is the most commonly occurring malignant brain and other CNS tumor in adults in the United States and is the most aggressive brain tumor with less than 10% of patients surviving beyond 5years [4]. 8600 Rockville Pike 18 studies used PFS6 as their primary endpoint while others include ORR (n=8) and other (n=3).

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