Kong, Anthony and Kirkham, Amanda J. and Savage, Joshua S. and Mant, Rhys and Lax, Siân and Good, James and Forster, Martin D. and Sacco, Joseph J. and Schipani, Stefano and Harrington, Kevin J. and Yap, Christina and Mehanna, Hisham (2024) Results and lessons learnt from the WISTERIA phase I trial combining AZD1775 with cisplatin pre- or post-operatively in head and neck cancer. BJC Reports, 2 (1): 6. ISSN 2731-9377
AI Summary:
WISTERIA was a prospective, parallel two-group, open-label, dose-finding, phase I clinical trial. The study aimed to determine the recommended dose and schedule of AZD1775 in combination with cisplatin in pre-operative Group A, or with cisplatinradiotherapy in post-operative Group B patients.AI Topics:
Background
Pre-clinical studies suggest AZD1775, a WEE1 kinase inhibitor, potentiates the activity of various chemotherapeutic agents.
Methods
WISTERIA was a prospective, parallel two-group, open-label, dose-finding, phase I clinical trial. Eligible patients had histologically confirmed oral, laryngeal, or hypopharyngeal squamous cell carcinoma, ECOG performance status 0/1, and aged ≥18-to-≤70 years. Primary outcomes were adverse events and defining recommended dose and schedule of AZD1775 in combination with cisplatin in pre-operative (Group A), or with cisplatin/radiotherapy in post-operative (Group B) patients. Dose determination was guided by a modified time-to-event continual reassessment method (mTITE-CRM).
Results
Between 30-Oct-2017 and 15-Jul-2019, nine patients were registered: Three into Group A and six into Group B. WISTERIA was closed early due to poor recruitment. Five dose-limiting toxicities (DLTs) were reported in four Group B patients. Seven serious adverse events were reported in four patients: One in Group A, and three in Group B. Three were related to treatment. No treatment-related deaths were reported.
Conclusions
WISTERIA did not complete its primary objectives due to poor recruitment and toxicities reported in Group B. However, use of the novel mTITE-CRM improved flexibility in reducing accrual suspension periods and should be considered for future trials in complex patient populations.
Kong, Anthony
Author
Homer, Jarrod J. and Winter, Stuart C. and Abbey, Elizabeth C. and Aga, Hiba and Agrawal, Reshma and ap Dafydd, Derfel and Arunjit, Takhar and Axon, Patrick and Aynsley, Eleanor and Bagwan, Izhar N. and Batra, Arun and Begg, Donna and Bernstein, Jonathan M. and Betts, Guy and Bicknell, Colin and Bisase, Brian and Brady, Grainne C. and Brennan, Peter and Brunet, Aina and Bryant, Val and Cantwell, Linda and Chandra, Ashish and Chengot, Preetha and Chua, Melvin L.K. and Clarke, Peter and Clunie, Gemma and Coffey, Margaret and Conlon, Clare and Conway, David I. and Cook, Florence and Cooper, Matthew R. and Costello, Declan and Cosway, Ben and Cozens, Neil J.A. and Creaney, Grant and Gahir, Daljit K. and Damato, Stephen and Davies, Joe and Davies, Katharine S. and Dragan, Alina D. and Du, Yong and Edmond, Mark R.D. and Fedele, Stefano and Finze, Harriet and Fleming, Jason C. and Foran, Bernadette H. and Fordham, Beth and Foridi, Mohammed M.A.S. and Freeman, Lesley and Frew, Katherine E. and Gaitonde, Pallavi and Gallyer, Victoria and Gibb, Fraser W. and Gore, Sinclair M. and Gormley, Mark and Govender, Roganie and Greedy, J. and Urbano, Teresa Guerrero and Gujral, Dorothy and Hamilton, David W. and Hardman, John C. and Harrington, Kevin and Holmes, Samantha and Homer, Jarrod J. and Howland, Deborah and Humphris, Gerald and Hunter, Keith D. and Ingarfield, Kate and Irving, Richard and Isand, Kristina and Jain, Yatin and Jauhar, Sachin and Jawad, Sarra and Jenkins, Glyndwr W. and Kanatas, Anastasios and Keohane, Stephen and Kerawala, Cyrus J. and Keys, William and King, Emma V. and Kong, Anthony and Lalloo, Fiona and Laws, Kirsten and Leong, Samuel C. and Lester, Shane and Levy, Miles and Lingley, Ken and Madani, Gitta and Mani, Navin and Matteucci, Paolo L. and Mayland, Catriona R and McCaul, James and McCaul, Lorna K. and McDonnell, Pádraig and McPartlin, Andrew and Mercadante, Valeria and Merchant, Zoe and Mihai, Radu and Moonim, Mufaddal T. and Moore, John and Nankivell, Paul and Natu, Sonali and Nelson, A. and Nenclares, Pablo and Newbold, Kate and Newland, Carrie and Nicol, Ailsa J. and Nixon, Iain J. and Obholzer, Rupert and O'Hara, James T. and Orr, S. and Paleri, Vinidh and Palmer, James and Parry, Rachel S. and Paterson, Claire and Patterson, Gillian and Patterson, Joanne M. and Payne, Miranda and Pearson, L. and Poller, David N. and Pollock, Jonathan and Porter, Stephen Ross and Potter, Matthew and Prestwich, Robin J.D. and Price, Ruth and Ragbir, Mani and Ranka, Meena S. and Robinson, Max and Roe, Justin W.G. and Roques, Tom and Rovira, Aleix and Sainuddin, Sajid and Salmon, I.J. and Sandison, Ann and Scarsbrook, Andy and Schache, Andrew G. and Scott, A. and Sellstrom, Diane and Semple, Cherith J. and Shah, Jagrit and Sharma, Praveen and Shaw, Richard J. and Siddiq, Somiah and Silva, Priyamal and Simo, Ricard and Singh, Rabin P. and Smith, Maria and Smith, Rebekah and Smith, Toby Oliver and Sood, Sanjai and Stafford, Francis W. and Steven, Neil and Stewart, Kay and Stoner, Lisa and Sweeney, Steve and Sykes, Andrew and Taylor, Carly L. and Thavaraj, Selvam and Thomson, David J. and Thornton, Jane and Tolley, Neil S. and Turnbull, Nancy and Vaidyanathan, Sriram and Vassiliou, Leandros and Waas, John and Wade-McBane, Kelly and Wakefield, Donna and Ward, Amy and Warner, Laura and Watson, Laura-Jayne and Watts, H. and Wilson, Christina and Winter, Stuart C. and Wong, Winson and Yip, Chui-Yan and Yip, Kent (2024) Head and Neck Cancer: United Kingdom National Multidisciplinary Guidelines, Sixth Edition. Journal of Laryngology and Otology, 138 (S1). S1-S224. ISSN 0022-2151
Kong, Anthony and Kirkham, Amanda J. and Savage, Joshua S. and Mant, Rhys and Lax, Siân and Good, James and Forster, Martin D. and Sacco, Joseph J. and Schipani, Stefano and Harrington, Kevin J. and Yap, Christina and Mehanna, Hisham (2024) Results and lessons learnt from the WISTERIA phase I trial combining AZD1775 with cisplatin pre- or post-operatively in head and neck cancer. BJC Reports, 2 (1): 6. ISSN 2731-9377
See full publications listKirkham, Amanda J.
Author
Kong, Anthony and Kirkham, Amanda J. and Savage, Joshua S. and Mant, Rhys and Lax, Siân and Good, James and Forster, Martin D. and Sacco, Joseph J. and Schipani, Stefano and Harrington, Kevin J. and Yap, Christina and Mehanna, Hisham (2024) Results and lessons learnt from the WISTERIA phase I trial combining AZD1775 with cisplatin pre- or post-operatively in head and neck cancer. BJC Reports, 2 (1): 6. ISSN 2731-9377
See full publications listSavage, Joshua S.
Author
Kong, Anthony and Kirkham, Amanda J. and Savage, Joshua S. and Mant, Rhys and Lax, Siân and Good, James and Forster, Martin D. and Sacco, Joseph J. and Schipani, Stefano and Harrington, Kevin J. and Yap, Christina and Mehanna, Hisham (2024) Results and lessons learnt from the WISTERIA phase I trial combining AZD1775 with cisplatin pre- or post-operatively in head and neck cancer. BJC Reports, 2 (1): 6. ISSN 2731-9377
See full publications listMant, Rhys
Author
Kong, Anthony and Kirkham, Amanda J. and Savage, Joshua S. and Mant, Rhys and Lax, Siân and Good, James and Forster, Martin D. and Sacco, Joseph J. and Schipani, Stefano and Harrington, Kevin J. and Yap, Christina and Mehanna, Hisham (2024) Results and lessons learnt from the WISTERIA phase I trial combining AZD1775 with cisplatin pre- or post-operatively in head and neck cancer. BJC Reports, 2 (1): 6. ISSN 2731-9377
See full publications listLax, Siân
Author
Kong, Anthony and Kirkham, Amanda J. and Savage, Joshua S. and Mant, Rhys and Lax, Siân and Good, James and Forster, Martin D. and Sacco, Joseph J. and Schipani, Stefano and Harrington, Kevin J. and Yap, Christina and Mehanna, Hisham (2024) Results and lessons learnt from the WISTERIA phase I trial combining AZD1775 with cisplatin pre- or post-operatively in head and neck cancer. BJC Reports, 2 (1): 6. ISSN 2731-9377
See full publications listGood, James
Author
Kong, Anthony and Kirkham, Amanda J. and Savage, Joshua S. and Mant, Rhys and Lax, Siân and Good, James and Forster, Martin D. and Sacco, Joseph J. and Schipani, Stefano and Harrington, Kevin J. and Yap, Christina and Mehanna, Hisham (2024) Results and lessons learnt from the WISTERIA phase I trial combining AZD1775 with cisplatin pre- or post-operatively in head and neck cancer. BJC Reports, 2 (1): 6. ISSN 2731-9377
See full publications listForster, Martin D.
Author
Frankell, Alexander M. and Dietzen, Michelle and Al Bakir, Maise and Lim, Emilia L. and Karasaki, Takahiro and Ward, Sophia and Veeriah, Selvaraju and Colliver, Emma and Huebner, Ariana and Bunkum, Abigail and Hill, Mark S. and Grigoriadis, Kristiana and Moore, David A. and Black, James R. M. and Liu, Wing Kin and Thol, Kerstin and Pich, Oriol and Watkins, Thomas B. K. and Naceur-Lombardelli, Cristina and Cook, Daniel E. and Salgado, Roberto and Wilson, Gareth A. and Bailey, Chris and Angelova, Mihaela and Bentham, Robert and Martínez-Ruiz, Carlos and Abbosh, Christopher and Nicholson, Andrew G. and Le Quesne, John and Biswas, Dhruva and Rosenthal, Rachel and Puttick, Clare and Hessey, Sonya and Lee, Claudia and Prymas, Paulina and Toncheva, Antonia and Smith, Jon and Xing, Wei and Nicod, Jerome and Price, Gillian and Kerr, Keith M. and Naidu, Babu and Middleton, Gary and Blyth, Kevin G. and Fennell, Dean A. and Forster, Martin D. and Lee, Siow Ming and Falzon, Mary and Hewish, Madeleine and Shackcloth, Michael J. and Lim, Eric and Benafif, Sarah and Russell, Peter and Boleti, Ekaterini and Krebs, Matthew G. and Lester, Jason F. and Papadatos-Pastos, Dionysis and Ahmad, Tanya and Thakrar, Ricky M. and Lawrence, David and Navani, Neal and Janes, Sam M. and Dive, Caroline and Blackhall, Fiona H. and Summers, Yvonne and Cave, Judith and Marafioti, Teresa and Herrero, Javier and Quezada, Sergio A. and Peggs, Karl S. and Schwarz, Roland F. and Van Loo, Peter and Miedema, Daniël M. and Birkbak, Nicolai J. and Hiley, Crispin T. and Hackshaw, Allan and Zaccaria, Simone and TRACERx Consortium and Jamal-Hanjani, Mariam and McGranahan, Nicholas and Swanton, Charles (2024) Author Correction: The evolution of lung cancer and impact of subclonal selection in TRACERx. Nature, 631 (8022): E15. ISSN 1476-4687
Kong, Anthony and Kirkham, Amanda J. and Savage, Joshua S. and Mant, Rhys and Lax, Siân and Good, James and Forster, Martin D. and Sacco, Joseph J. and Schipani, Stefano and Harrington, Kevin J. and Yap, Christina and Mehanna, Hisham (2024) Results and lessons learnt from the WISTERIA phase I trial combining AZD1775 with cisplatin pre- or post-operatively in head and neck cancer. BJC Reports, 2 (1): 6. ISSN 2731-9377
See full publications listSacco, Joseph J.
Author
Kong, Anthony and Kirkham, Amanda J. and Savage, Joshua S. and Mant, Rhys and Lax, Siân and Good, James and Forster, Martin D. and Sacco, Joseph J. and Schipani, Stefano and Harrington, Kevin J. and Yap, Christina and Mehanna, Hisham (2024) Results and lessons learnt from the WISTERIA phase I trial combining AZD1775 with cisplatin pre- or post-operatively in head and neck cancer. BJC Reports, 2 (1): 6. ISSN 2731-9377
See full publications listSchipani, Stefano
Author
Kong, Anthony and Kirkham, Amanda J. and Savage, Joshua S. and Mant, Rhys and Lax, Siân and Good, James and Forster, Martin D. and Sacco, Joseph J. and Schipani, Stefano and Harrington, Kevin J. and Yap, Christina and Mehanna, Hisham (2024) Results and lessons learnt from the WISTERIA phase I trial combining AZD1775 with cisplatin pre- or post-operatively in head and neck cancer. BJC Reports, 2 (1): 6. ISSN 2731-9377
See full publications listHarrington, Kevin J.
Author
Kong, Anthony and Kirkham, Amanda J. and Savage, Joshua S. and Mant, Rhys and Lax, Siân and Good, James and Forster, Martin D. and Sacco, Joseph J. and Schipani, Stefano and Harrington, Kevin J. and Yap, Christina and Mehanna, Hisham (2024) Results and lessons learnt from the WISTERIA phase I trial combining AZD1775 with cisplatin pre- or post-operatively in head and neck cancer. BJC Reports, 2 (1): 6. ISSN 2731-9377
See full publications listYap, Christina
Author
Kong, Anthony and Kirkham, Amanda J. and Savage, Joshua S. and Mant, Rhys and Lax, Siân and Good, James and Forster, Martin D. and Sacco, Joseph J. and Schipani, Stefano and Harrington, Kevin J. and Yap, Christina and Mehanna, Hisham (2024) Results and lessons learnt from the WISTERIA phase I trial combining AZD1775 with cisplatin pre- or post-operatively in head and neck cancer. BJC Reports, 2 (1): 6. ISSN 2731-9377
See full publications listMehanna, Hisham
Author
Kong, Anthony and Kirkham, Amanda J. and Savage, Joshua S. and Mant, Rhys and Lax, Siân and Good, James and Forster, Martin D. and Sacco, Joseph J. and Schipani, Stefano and Harrington, Kevin J. and Yap, Christina and Mehanna, Hisham (2024) Results and lessons learnt from the WISTERIA phase I trial combining AZD1775 with cisplatin pre- or post-operatively in head and neck cancer. BJC Reports, 2 (1): 6. ISSN 2731-9377
See full publications listAvailable under License Creative Commons Attribution.
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