ATLANTIS: a randomised multi-arm phase II biomarker-directed umbrella screening trial of maintenance targeted therapy after chemotherapy in patients with advanced or metastatic urothelial cancer

被引：12

作者：

Fulton, Ben ^{[1
]}

Jones, Robert ^{[2
]}

Powles, Thomas ^{[3
]}

Crabb, Simon ^{[4
]}

Paul, James ^{[5
]}

Birtle, Alison ^{[6
]}

Chowdhury, Simon ^{[7
]}

Hussain, Syed ^{[8
]}

Morris, Anna ^{[5
]}

Soulis, Eileen ^{[5
]}

Morrison, Paula ^{[5
]}

机构：

[1] Beatson West Scotland Canc Ctr, 1053 Great Western Rd, Glasgow G12 0YN, Lanark, Scotland

[2] Inst Canc Sci, Switchback Rd, Glasgow G61 1QH, Lanark, Scotland

[3] Queen Mary Univ London, Barts Canc Inst, London EC1M 6BQ, England

[4] Univ Southampton, Fac Med, 12 Univ Rd, Southampton SO17 1BJ, Hants, England

[5] Beatson West Scotland Canc Ctr, Canc Res UK Clin Trials Unit, 1053 Great Western Rd, Glasgow G12 0YN, Lanark, Scotland

[6] Univ Manchester, Sch Canc Sci, Oxford Rd, Manchester M13 9PL, Lancs, England

[7] Guys & St Thomas NHS Fdn Trust, London SE1 9RT, England

[8] Univ Sheffield, Acad Unit Oncol, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England

来源：

TRIALS | 2020年 / 21卷 / 01期

关键词：

Urothelial cancer; Precision medicine; Biomarker; CISPLATIN-INELIGIBLE PATIENTS; SINGLE-ARM; 1ST-LINE TREATMENT; BLADDER-CANCER; DOUBLE-BLIND; OPEN-LABEL; MULTICENTER; CARCINOMA; GEMCITABINE; PEMBROLIZUMAB;

D O I：

10.1186/s13063-020-04283-5

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

BackgroundMetastatic urothelial cancer (UC) is the eighth most common cause of cancer death in the UK. Standard first-line treatment, for most patients, is cytotoxic chemotherapy. Although UC is initially sensitive to chemotherapy, relapse is almost inevitable and outcomes are poor; median overall survival is 8months. Therefore, there is an urgent need for novel therapies to improve outcomes for this patient group.MethodsATLANTIS is a randomised phase II umbrella-design screening trial of maintenance therapy in biomarker-defined subgroups of patients with advanced UC. The primary end point is progression-free survival, and the study involves over 30 UK cancer centres.DiscussionATLANTIS is the first study in the UK to employ a precision-medicine approach to patients with UC for maintenance treatment. Agents with a positive efficacy signal will proceed to randomised phase III trials to confirm the activity of novel, biologically stratified therapies in UC.RegistrationATLANTIS trial EudraCT number 2015-003249-25. ISRCTN25859465.

引用

页数：7

共 22 条

[1]

Apolo AB, 2013, J CLIN ONCOL, V31

[2] First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study [J].

Balar, Arjun V. ;

Castellano, Daniel ;

O'Donnell, Peter H. ;

Grivas, Petros ;

Vuky, Jacqueline ;

Powles, Thomas ;

Plimack, Elizabeth R. ;

Hahn, Noah M. ;

de Wit, Ronald ;

Pang, Lei ;

Savage, Mary J. ;

Perini, Rodolfo F. ;

Keefe, Stephen M. ;

Bajorin, Dean ;

Bellmunt, Joaquim .

LANCET ONCOLOGY, 2017, 18 (11) :1483-1492

[3] Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial [J].

Balar, Arjun V. ;

Galsky, Matthew D. ;

Rosenberg, Jonathan E. ;

Powles, Thomas ;

Petrylak, Daniel P. ;

Bellmunt, Joaquim ;

Loriot, Yohann ;

Necchi, Andrea ;

Hoffman-Censits, Jean ;

Perez-Gracia, Jose Luis ;

Dawson, Nancy A. ;

van der Heijden, Michiel S. ;

Dreicer, Robert ;

Srinivas, Sandy ;

Retz, Margitta M. ;

Joseph, Richard W. ;

Drakaki, Alexandra ;

Vaishampayan, Ulka N. ;

Sridhar, Srikala S. ;

Quinn, David I. ;

Duran, Ignacio ;

Shaffer, David R. ;

Eigl, Bernhard J. ;

Grivas, Petros D. ;

Yu, Evan Y. ;

Li, Shi ;

Kadel, Edward E., III ;

Boyd, Zachary ;

Bourgon, Richard ;

Hegde, Priti S. ;

Mariathasan, Sanjeev ;

Thastrom, AnnChristine ;

Abidoye, Oyewale O. ;

Fine, Gregg D. ;

Bajorin, Dean F. .

LANCET, 2017, 389 (10064) :67-76

[4]

Beer TM, 2014, NEW ENGL J MED, V371, P424, DOI 10.1056/NEJMoa1405095

[5] Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma [J].

Bellmunt, J. ;

de Wit, R. ;

Vaughn, D. J. ;

Fradet, Y. ;

Lee, J. -L. ;

Fong, L. ;

Vogelzang, N. J. ;

Climent, M. A. ;

Petrylak, D. P. ;

Choueiri, T. K. ;

Necchi, A. ;

Gerritsen, W. ;

Gurney, H. ;

Quinn, D. I. ;

Culine, S. ;

Sternberg, C. N. ;

Mai, Y. ;

Poehlein, C. H. ;

Perini, R. F. ;

Bajorin, D. F. .

NEW ENGLAND JOURNAL OF MEDICINE, 2017, 376 (11) :1015-1026

[6] Overexpression of c-met as a prognostic indicator for transitional cell carcinoma of the urinary bladder:: A comparison with p53 nuclear accumulation [J].

Cheng, HL ;

Trink, B ;

Tzai, TS ;

Liu, HS ;

Chan, SH ;

Ho, CL ;

Sidransky, D ;

Chow, NH .

JOURNAL OF CLINICAL ONCOLOGY, 2002, 20 (06) :1544-1550

[7] Randomized Phase II/III Trial Assessing Gemcitabine/Carboplatin and Methotrexate/Carboplatin/Vinblastine in Patients With Advanced Urothelial Cancer Who Are Unfit for Cisplatin-Based Chemotherapy: EORTC Study 30986 [J].

De Santis, Maria ;

Bellmunt, Joaquim ;

Mead, Graham ;

Kerst, J. Martijn ;

Leahy, Michael ;

Maroto, Pablo ;

Gil, Thierry ;

Marreaud, Sandrine ;

Daugaard, Gedske ;

Skoneczna, Iwona ;

Collette, Sandra ;

Lorent, Julie ;

de Wit, Ronald ;

Sylvester, Richard .

JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (02) :191-199

[8] Cabozantinib in Progressive Medullary Thyroid Cancer [J].

Elisei, Rossella ;

Schlumberger, Martin J. ;

Mueller, Stefan P. ;

Schoffski, Patrick ;

Brose, Marcia S. ;

Shah, Manisha H. ;

Licitra, Lisa ;

Jarzab, Barbara ;

Medvedev, Viktor ;

Kreissl, Michael C. ;

Niederle, Bruno ;

Cohen, Ezra E. W. ;

Wirth, Lori J. ;

Ali, Haythem ;

Hessel, Colin ;

Yaron, Yifah ;

Ball, Douglas ;

Nelkin, Barry ;

Sherman, Steven I. .

JOURNAL OF CLINICAL ONCOLOGY, 2013, 31 (29) :3639-+

[9] Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy [J].

Farmer, H ;

McCabe, N ;

Lord, CJ ;

Tutt, ANJ ;

Johnson, DA ;

Richardson, TB ;

Santarosa, M ;

Dillon, KJ ;

Hickson, I ;

Knights, C ;

Martin, NMB ;

Jackson, SP ;

Smith, GCM ;

Ashworth, A .

NATURE, 2005, 434 (7035) :917-921

[10] SUCCINCT: An Open-label, Single-arm, Non-randomised, Phase 2 Trial of Gemcitabine and Cisplatin Chemotherapy in Combination with Sunitinib as First-line Treatment for Patients with Advanced Urothelial Carcinoma [J].

Geldart, Thomas ;

Chester, John ;

Casbard, Angela ;

Crabb, Simon ;

Elliott, Tony ;

Protheroe, Andrew ;

Huddart, Robert A. ;

Mead, Graham ;

Barber, Jim ;

Jones, Robert J. ;

Smith, Joanna ;

Cowles, Robert ;

Evans, Jessica ;

Griffiths, Gareth .

EUROPEAN UROLOGY, 2015, 67 (04) :599-602

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