Topic: National Cancer Research Network
Conditions
Interventions
The patient numbers in this dose escalation phase I are estimated and will depend on the frequency and severity of adverse events. A modified continual reassessment method (mCRM) design will be used t
Sponsors
University College London (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed high risk locally advanced HNSCC (TNM staging T(any) N2 or N3 M0, bulky T3 or T4 N(any) M0) who would normally be offered cisplatin-based radical chemoradiotherapy 2. Estimated life expectancy of at least 12 weeks 3. WHO performance status of 0 or 1 4. Aged more than or equal to 18 years 5. Adequate organ function: 5.1. Absolute neutrophils =1.5 x 10*9/L 5.2. Platelets =100 x 10*9/L 5.3. Haemoglobin =10g/dl (to be maintained above 12g/dl whilst on CRT treatment) 5.4. Creatinine =1.5 x ULN 5.5. Glomerular filtration rate (GFR) =60 ml/min 5.6. Serum bilirubin = 1.25 x ULN 5.7. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) = 2.5 x ULN 6. Patients willing to use contraception for the duration of the trial and for six months post treatment 7. Able to give informed consent 8. Patient is willing and able to comply with the protocol for the duration of the study, including the treatment plan investigations required and follow up visits; Target Gender: Male & Female ; Lower Age Limit 18 years
Exclusion criteria
Exclusion criteria: 1. Head & neck cancers of the following types: Nasopharyngeal and paranasal sinus tumours, oral cavity tumours (tumours of the oral cavity) 2. Human Papilloma Virus positive oropharyngeal tumours (tonsillar and tongue base tumours) 3. Confirmed distant metastatic disease 4. Previous chemotherapy or radiotherapy for the treatment of HNSCC tumour 5. Previous therapy with a PARP inhibitor 6. Previous chemotherapy, immunotherapy or radiotherapy within the last 28 days prior to registration 7. Prior history of malignancy, except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, breast or prostate, and unless the patient has been free of malignancy for a period of 3 years prior to first dose of trial drug 8. Women who are pregnant or lactating 9. Pre-existing gastrointestinal disorders that may interfere with the delivery or absorption of trial drugs 10. Peripheral neuropathy > Grade 2 (lower grade neuropathy considered significant by treating clinician may be considered an exclusion criterion) 11. Significant hearing difficulties (patients with mildly impaired hearing must be made aware of potential ototoxicity) 12. Any serious and/or unstable pre-existing medical, psychiatric or other condition that, in the treating clinician?s judgement, could interfere with patient safety or obtaining informed consent 13. Known hepatitis B or C infection 14. Immunocompromised patients [e.g. Known human imunodeficiency virus (HIV) positive status] 15. Active uncontrolled infection 16. The current use of drugs which are known to inhibit Cytochrome P450 3A4 (CYP3A4) which cannot be discontinued for the duration of trial treatment
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| 1. Other efficacy endpoints: complete response rate (cRR) 2. Time to loco-regional and any progression | — |
Primary
| Measure | Time frame |
|---|---|
| To assess the frequency of Dose Limiting Toxicities (DLTs) and adverse events. | — |
Countries
United Kingdom
Outcome results
None listed