دورية أكاديمية
Tailoring early-phase clinical trial design to address multiple research objectives.
| العنوان: | Tailoring early-phase clinical trial design to address multiple research objectives. |
|---|---|
| المؤلفون: | Wages NA; Division of Translational Research and Applied Statistics, Department of Public Health Sciences, University of Virginia, P.O. Box 800717, Charlottesville, VA, USA. nwages@virginia.edu., Slingluff CL Jr; Division of Surgical Oncology, Department of Surgery, University of Virginia, Charlottesville, VA, USA., Bullock TN; Department of Pathology, University of Virginia, Charlottesville, VA, USA., Petroni GR; Division of Translational Research and Applied Statistics, Department of Public Health Sciences, University of Virginia, P.O. Box 800717, Charlottesville, VA, USA. |
| المصدر: | Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2020 Jan; Vol. 69 (1), pp. 95-102. Date of Electronic Publication: 2019 Dec 05. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer Verlag Country of Publication: Germany NLM ID: 8605732 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0851 (Electronic) Linking ISSN: 03407004 NLM ISO Abbreviation: Cancer Immunol Immunother Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Berlin : Springer Verlag Original Publication: Berlin ; New York, NY : Springer International, c1982- |
| مواضيع طبية MeSH: | Research Design*, Immunotherapy/*methods , Melanoma/*therapy , Skin Neoplasms/*therapy, Antineoplastic Agents, Immunological/pharmacology ; Antineoplastic Agents, Immunological/therapeutic use ; CD40 Antigens/antagonists & inhibitors ; CD40 Antigens/immunology ; Cancer Vaccines/therapeutic use ; Clinical Trials, Phase I as Topic ; Clinical Trials, Phase II as Topic ; Combined Modality Therapy/methods ; Drug Development ; Humans ; Melanoma/immunology ; Skin Neoplasms/immunology ; Tumor Necrosis Factor Receptor Superfamily, Member 7/antagonists & inhibitors ; Tumor Necrosis Factor Receptor Superfamily, Member 7/immunology |
| مستخلص: | Introduction: In contemporary oncology drug development, implementation of novel early-phase designs with the ability to address multiple research objectives is needed to better refine regimens. This paper describes an adaptive design strategy for identifying a range of optimal regimens based on two endpoints within multiple cohorts. The proposed design was developed to address objectives in an early-phase trial of cancer vaccines in combination with agonistic antibodies to CD40 and CD27. Materials and Methods: We describe a model-based design strategy that was developed for a trial evaluating the safety and immunogenicity of vaccination with (1) peptides plus CD40 antibody and TLR3 ligand, (2) systemic administration of an agonistic CD27 antibody, and (3) to assess immune response from (1) and (2) compared to optimal controls in participants with stage IIB-IV melanoma. Results and Conclusions: The proposed design is a practical adaptive method for use with combined immunotherapy regimens with multiple objectives within multiple cohorts of interest. Further advances in the effectiveness of cancer immunotherapies will require new approaches that include redefining optimal strategies to take multiple regimens forward into later phases, incorporating additional endpoints in the dose selection process and testing drug combination therapies to improve efficacy and reduce toxicity. Our goal is to facilitate the acceptance and application of more novel designs in contemporary early development trials. |
| References: | N Engl J Med. 2011 Jun 2;364(22):2119-27. (PMID: 21631324) Stat Med. 2017 Jan 30;36(2):215-224. (PMID: 26928191) J Immunother Cancer. 2019 Jun 27;7(1):163. (PMID: 31248461) J Immunol. 2009 Jun 15;182(12):7398-407. (PMID: 19494262) Clin Cancer Res. 2012 Dec 1;18(23):6497-508. (PMID: 23032745) N Engl J Med. 2008 Jun 19;358(25):2704-15. (PMID: 18565863) Clin Cancer Res. 2016 Jun 1;22(11):2623-9. (PMID: 27250933) J Natl Cancer Inst. 2019 Feb 1;111(2):118-128. (PMID: 30561713) Stat Med. 2009 Oct 30;28(24):3012-28. (PMID: 19672839) Clin Cancer Res. 2013 Aug 1;19(15):4228-38. (PMID: 23653149) Clin Cancer Res. 2019 Jan 15;25(2):819-827. (PMID: 30327310) Stat Med. 2019 Mar 30;38(7):1170-1189. (PMID: 30368868) Clin Cancer Res. 2014 Sep 15;20(18):4758-67. (PMID: 25037736) J Clin Oncol. 2015 Jul 1;33(19):2221-5. (PMID: 25940721) J Transl Med. 2007 Feb 12;5:10. (PMID: 17295916) Ann Oncol. 2015 Sep;26(9):1808-1812. (PMID: 26088197) Contemp Clin Trials. 2015 Mar;41:172-9. (PMID: 25638752) Nat Med. 2004 Sep;10(9):909-15. (PMID: 15340416) J Immunother Cancer. 2018 Mar 6;6(1):19. (PMID: 29510745) J Immunother Cancer. 2018 Aug 22;6(1):81. (PMID: 30134959) Stat Med. 2017 Jan 15;36(1):43-53. (PMID: 27545299) Ann Oncol. 2017 Apr 1;28(4):696-701. (PMID: 28011450) J Clin Invest. 2018 Apr 2;128(4):1338-1354. (PMID: 29480817) Clin Trials. 2009 Jun;6(3):227-38. (PMID: 19528132) Clin Cancer Res. 2007 Nov 1;13(21):6386-95. (PMID: 17975151) Biometrics. 2011 Dec;67(4):1555-63. (PMID: 21361888) Pharm Stat. 2011 May-Jun;10(3):218-26. (PMID: 20922817) Ann Oncol. 2015 Apr;26(4):669-674. (PMID: 25403591) J Clin Oncol. 2014 Aug 10;32(23):2505-11. (PMID: 24982451) Trends Immunol. 2013 Feb;34(2):90-8. (PMID: 23031830) N Engl J Med. 2010 Jul 29;363(5):411-22. (PMID: 20818862) Oncoimmunology. 2018 Feb 22;7(6):e1433516. (PMID: 29872563) J Clin Oncol. 2011 Jul 20;29(21):2924-32. (PMID: 21690475) Clin Trials. 2019 Feb;16(1):32-40. (PMID: 30309262) Biometrics. 1990 Mar;46(1):33-48. (PMID: 2350571) |
| معلومات مُعتمدة: | R01 CA142859 United States CA NCI NIH HHS; Team Science Award United States MRA Melanoma Research Alliance; K25CA181638 United States CA NCI NIH HHS; R01CA142859 United States CA NCI NIH HHS; K25 CA181638 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: Adaptive design; Cancer vaccines; Combination; Early-phase |
| المشرفين على المادة: | 0 (Antineoplastic Agents, Immunological) 0 (CD40 Antigens) 0 (Cancer Vaccines) 0 (Tumor Necrosis Factor Receptor Superfamily, Member 7) |
| تواريخ الأحداث: | Date Created: 20191207 Date Completed: 20200214 Latest Revision: 20240427 |
| رمز التحديث: | 20240427 |
| مُعرف محوري في PubMed: | PMC6952569 |
| DOI: | 10.1007/s00262-019-02442-5 |
| PMID: | 31807879 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1432-0851 |
|---|---|
| DOI: | 10.1007/s00262-019-02442-5 |