Phase I Study of Olaparib Combined With Cisplatin-based Chemoradiotherapy to Treat Locally Advanced Head and Neck Cancer

Launched by UNIVERSITY COLLEGE, LONDON · Dec 2, 2014

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment approach for patients with locally advanced head and neck cancer. The study is looking to find the best dose and schedule for a drug called olaparib when combined with standard chemotherapy and radiation therapy using cisplatin. This trial is designed for patients who are at high risk and would typically receive cisplatin-based chemoradiotherapy.

To be eligible, participants need to be at least 18 years old and have a confirmed diagnosis of high-risk squamous cell carcinoma in the head and neck. They should also have a life expectancy of at least 16 weeks and be in good overall health, with adequate function of their blood cells, kidneys, and liver. Participants will take olaparib tablets and be monitored closely for safety and side effects throughout the study. It’s important to note that this trial is currently active but not recruiting new participants, and it includes specific criteria to ensure the safety and well-being of those involved.

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Eligibility criteria

• Inclusion Criteria:
• • 1. Histologically confirmed high-risk locally advanced HNSCC, patients who would normally be offered cisplatin-based radical chemoradiotherapy
• • 2. Estimated life expectancy of at least 16 weeks
• • 3. WHO performance status 0 or 1
• • 4. Aged ≥18 years
• • 5. Adequate bone marrow function: absolute neutrophils grade 0 or 1, platelets grade 0 or 1, haemoglobin grade 0 or 1
• • 6. Adequate renal function: Creatinine grade 0 or 1, Calculated GFR ≥60 mL/min (if calculated value is \<60 mL/min then an isotope GFR assessment should be performed or an estimation from 24h urine collection)
• • 7. Adequate liver function: Serum bilirubin grade 0 or 1, AST or ALT grade 0 or 1
• • 8. Patients must be able to swallow olaparib tablets
• • 9. Willing to use contraception for the duration of the trial treatment and for six months after completion of treatment
• • 10. Able to give informed consent
• • 11. Patients willing and able to comply with the protocol for the duration of the study
• Exclusion Criteria:
• • 1. Head \& neck cancers of the following types: Nasopharyngeal and paranasal sinus tumours, Oral squamous cell carcinomas (tumours of the oral cavity), Low risk Human Papilloma Virus positive oropharyngeal tumours (tonsillar and tongue base tumours)
• • 2. Confirmed distant metastatic disease
• • 3. Previous chemotherapy or radiotherapy for the treatment of HNSCC tumour
• • 4. Previous therapy with a PARP inhibitor
• • 5. Chemotherapy, immunotherapy or radiotherapy within 28 days prior to registration
• • 6. Prior history of malignancy, except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, breast or prostate. Patient must have been free of malignancy for a period of 3 years prior to first dose of trial drug
• • 7. Women who are pregnant or lactating
• • 8. Pre-existing gastrointestinal disorders that may interfere with the delivery or absorption of olaparib
• • 9. Grade 3 or 4 peripheral neuropathy - If considered significant by the treating clinician a lower grade neuropathy may be considered as exclusion criterion
• • 10. Significant hearing difficulties or tinnitus (deaf patients can be included) - Whilst not excluded, patients with mildly impaired hearing or tinnitus must be made aware of potential ototoxicity and may choose not to be included. If included, it is recommended that audiograms be carried out at baseline.
• • 11. Any serious and/or unstable pre-existing medical, psychiatric or other condition that, in the treating clinician's judgment, could interfere with patient safety or obtaining informed consent
• • 12. Known hepatitis B or C infection (testing for Hepatitis and HIV for the trial is not mandatory)
• • 13. Immunocompromised patients (e.g. known HIV positive status)
• • 14. Active uncontrolled infection
• • 15. The current use of drugs which are known to inhibit or induce CYP3A4
• • 16. Resting ECG with QTc \> 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
• • 17. Patients with myelodysplastic syndrome/acute myeloid leukaemia.
• • 18. Patients with a known hypersensitivity to olaparib or any of the excipients of the product.