Phase I trial of WEE1 inhibition with chemotherapy and radiotherapy as adjuvant treatment, and a window of opportunity trial with cisplatin in patients with head and neck cancer: the WISTERIA trial protocol
Introduction Patients with head and neck squamous cell carcinoma with locally advanced disease often require multimodality treatment with surgery, radiotherapy and/or chemotherapy. Adjuvant radiotherapy with concurrent chemotherapy is offered to patients with high-risk pathological features postsurg...
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BMJ Publishing Group
2020-03-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/10/3/e033009.full |
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| author | Martin Forster Joseph Sacco Christina Yap Kevin Harrington Hisham Mehanna Anthony Kong James Good Amanda Kirkham Joshua Savage Rhys Mant Laura Llewellyn Joanna Parish Rachel Spruce Stefano Schipani Patrick Murray Gary Middleton |
| author_facet | Martin Forster Joseph Sacco Christina Yap Kevin Harrington Hisham Mehanna Anthony Kong James Good Amanda Kirkham Joshua Savage Rhys Mant Laura Llewellyn Joanna Parish Rachel Spruce Stefano Schipani Patrick Murray Gary Middleton |
| author_sort | Martin Forster |
| collection | DOAJ |
| description | Introduction Patients with head and neck squamous cell carcinoma with locally advanced disease often require multimodality treatment with surgery, radiotherapy and/or chemotherapy. Adjuvant radiotherapy with concurrent chemotherapy is offered to patients with high-risk pathological features postsurgery. While cure rates are improved, overall survival remains suboptimal and treatment has a significant negative impact on quality of life.Cell cycle checkpoint kinase inhibition is a promising method to selectively potentiate the therapeutic effects of chemoradiation. Our hypothesis is that combining chemoradiation with a WEE1 inhibitor will affect the biological response to DNA damage caused by cisplatin and radiation, thereby enhancing clinical outcomes, without increased toxicity. This trial explores the associated effect of WEE1 kinase inhibitor adavosertib (AZD1775).Methods and analysis This phase I dose-finding, open-label, multicentre trial aims to determine the highest safe dose of AZD1775 in combination with cisplatin chemotherapy preoperatively (group A) as a window of opportunity trial, and in combination with postoperative cisplatin-based chemoradiation (group B).Modified time-to-event continual reassessment method will determine the recommended dose, recruiting up to 21 patients per group. Primary outcomes are recommended doses with predefined target dose-limiting toxicity probabilities of 25% monitored up to 42 days (group A), and 30% monitored up to 12 weeks (group B). Secondary outcomes are disease-free survival times (groups A and B). Exploratory objectives are evaluation of pharmacodynamic (PD) effects, identification and correlation of potential biomarkers with PD markers of DNA damage, determine rate of resection status and surgical complications for group A; and quality of life in group B.Ethics and dissemination Research Ethics Committee, Edgbaston, West Midlands (REC reference 16/WM/0501) initial approval received on 18/01/2017. Results will be disseminated via peer-reviewed publication and presentation at international conferences.Trial registration number ISRCTN76291951 and NCT03028766. |
| format | Article |
| id | doaj-art-c0d06a73a4e74b4ea1096d13b337f16f |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2020-03-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-c0d06a73a4e74b4ea1096d13b337f16f2024-12-06T03:10:11ZengBMJ Publishing GroupBMJ Open2044-60552020-03-0110310.1136/bmjopen-2019-033009Phase I trial of WEE1 inhibition with chemotherapy and radiotherapy as adjuvant treatment, and a window of opportunity trial with cisplatin in patients with head and neck cancer: the WISTERIA trial protocolMartin Forster0Joseph Sacco1Christina Yap2Kevin Harrington3Hisham Mehanna4Anthony Kong5James Good6Amanda Kirkham7Joshua Savage8Rhys Mant9Laura Llewellyn10Joanna Parish11Rachel Spruce12Stefano Schipani13Patrick Murray14Gary Middleton153UCL/University College London NHS, London, London, UK3Clatterbridge Cancer Center, Liverpool, UKprofessor of clinical trials biostatistics7 Institute of Cancer Research, London, UK2 Institute for Head and Neck Studies and Education, Department of Cancer and Genomic Sciences, College of Medicine and Health, University of Birmingham, Birmingham, UKComprehensive Cancer Centre, King`s College London, London, UKDepartment of Stereotactic and MR-guided Radiotherapy, GenesisCare UK, Oxford, UK3 Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UKCancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham, Birmingham, UKCancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham, Birmingham, UK4 SIMBEC Research Limited, Merthyr Tydfil, Glamorgan, UK1 Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK1 Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UKClinical Oncology, Beatson West of Scotland Cancer Centre, Glasgow, UK9 Leeds Teaching Hospitals NHS Trust, Leeds, UK11 Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UKIntroduction Patients with head and neck squamous cell carcinoma with locally advanced disease often require multimodality treatment with surgery, radiotherapy and/or chemotherapy. Adjuvant radiotherapy with concurrent chemotherapy is offered to patients with high-risk pathological features postsurgery. While cure rates are improved, overall survival remains suboptimal and treatment has a significant negative impact on quality of life.Cell cycle checkpoint kinase inhibition is a promising method to selectively potentiate the therapeutic effects of chemoradiation. Our hypothesis is that combining chemoradiation with a WEE1 inhibitor will affect the biological response to DNA damage caused by cisplatin and radiation, thereby enhancing clinical outcomes, without increased toxicity. This trial explores the associated effect of WEE1 kinase inhibitor adavosertib (AZD1775).Methods and analysis This phase I dose-finding, open-label, multicentre trial aims to determine the highest safe dose of AZD1775 in combination with cisplatin chemotherapy preoperatively (group A) as a window of opportunity trial, and in combination with postoperative cisplatin-based chemoradiation (group B).Modified time-to-event continual reassessment method will determine the recommended dose, recruiting up to 21 patients per group. Primary outcomes are recommended doses with predefined target dose-limiting toxicity probabilities of 25% monitored up to 42 days (group A), and 30% monitored up to 12 weeks (group B). Secondary outcomes are disease-free survival times (groups A and B). Exploratory objectives are evaluation of pharmacodynamic (PD) effects, identification and correlation of potential biomarkers with PD markers of DNA damage, determine rate of resection status and surgical complications for group A; and quality of life in group B.Ethics and dissemination Research Ethics Committee, Edgbaston, West Midlands (REC reference 16/WM/0501) initial approval received on 18/01/2017. Results will be disseminated via peer-reviewed publication and presentation at international conferences.Trial registration number ISRCTN76291951 and NCT03028766.https://bmjopen.bmj.com/content/10/3/e033009.full |
| spellingShingle | Martin Forster Joseph Sacco Christina Yap Kevin Harrington Hisham Mehanna Anthony Kong James Good Amanda Kirkham Joshua Savage Rhys Mant Laura Llewellyn Joanna Parish Rachel Spruce Stefano Schipani Patrick Murray Gary Middleton Phase I trial of WEE1 inhibition with chemotherapy and radiotherapy as adjuvant treatment, and a window of opportunity trial with cisplatin in patients with head and neck cancer: the WISTERIA trial protocol BMJ Open |
| title | Phase I trial of WEE1 inhibition with chemotherapy and radiotherapy as adjuvant treatment, and a window of opportunity trial with cisplatin in patients with head and neck cancer: the WISTERIA trial protocol |
| title_full | Phase I trial of WEE1 inhibition with chemotherapy and radiotherapy as adjuvant treatment, and a window of opportunity trial with cisplatin in patients with head and neck cancer: the WISTERIA trial protocol |
| title_fullStr | Phase I trial of WEE1 inhibition with chemotherapy and radiotherapy as adjuvant treatment, and a window of opportunity trial with cisplatin in patients with head and neck cancer: the WISTERIA trial protocol |
| title_full_unstemmed | Phase I trial of WEE1 inhibition with chemotherapy and radiotherapy as adjuvant treatment, and a window of opportunity trial with cisplatin in patients with head and neck cancer: the WISTERIA trial protocol |
| title_short | Phase I trial of WEE1 inhibition with chemotherapy and radiotherapy as adjuvant treatment, and a window of opportunity trial with cisplatin in patients with head and neck cancer: the WISTERIA trial protocol |
| title_sort | phase i trial of wee1 inhibition with chemotherapy and radiotherapy as adjuvant treatment and a window of opportunity trial with cisplatin in patients with head and neck cancer the wisteria trial protocol |
| url | https://bmjopen.bmj.com/content/10/3/e033009.full |
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