ADePT-DDR Trial, version 3.0, 07-Oct-2020
Research type
Research Study
Full title
Accelerating the Development and implementation of Personalised Treatments of DNA Damage Response agents and radiotherapy +/- immunotherapy for head and neck squamous cell cancer
IRAS ID
277083
Contact name
Hisham Mehanna
Contact email
Sponsor organisation
University of Birmingham
Eudract number
2020-001034-35
ISRCTN Number
ISRCTN66274524
Duration of Study in the UK
5 years, 0 months, 0 days
Research summary
Head and neck squamous cell carcinoma (HNSCC) is a disease in which malignant cells form. These cells can arise in the mouth, middle part of the throat, lower part of the throat or the voice box. In the curative setting, these patients often require treatment with surgery, radiotherapy and/or chemotherapy. Primary radiotherapy with concurrent platin-based chemotherapy is often offered to those with advanced head and neck cancer. However, it has not been shown to improve survival in patients aged over 70 years old and platin-based chemotherapy is not suitable for patients with poor kidney function. This results in these patients having suboptimal survival and cure rates.
Radiotherapy plays an essential role in cancer treatment. Many patients receive radical radiation or chemoradiation for localised disease; however, despite recent advances in radiation techniques and the use of concomitant chemoradiotherapy, patients with solid tumours such as head and neck cancers have suboptimal cure rates.
DNA damage repair inhibition is a promising means by which the therapeutic effects of ionising radiation could be increased in cancer cells. Combining radiation with an inhibitor of DNA damage repair enzymes may enhance clinical outcomes without a substantial increase in toxicity. In addition, adding immunotherapy treatments to radiotherapy may potentiate its killing effect tumour.The purpose of the first part of the study is to investigate the safety and effects of a DNA-Damage Inhibitor, AZD6738 (Ceralasertib), when given in combination with radiotherapy in patients with HNSCC deemed unsuitable for standard platin-based chemotherapy. The trial will run across~ 18 sites in the UK. The first part of the trial involves finding the maximum tolerated dose of AZD6738 (Ceralasertib), which will take approximately 60 months to recruit and assess for safety. Also incorporated is a Quality of Life component and optional blood and tissue collection for blood analysis and translational research.
REC name
South Central - Berkshire B Research Ethics Committee
REC reference
20/SC/0319
Date of REC Opinion
15 Oct 2020
REC opinion
Further Information Favourable Opinion