Phase I Study of Olaparib With Cisplatin Based Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck (ORCA)
The aim of this study is to find the safe dose and best dosing schedule of olaparib to give in combination with cisplatin based chemoradiotherapy (CRT) in patients with locally advanced head and neck cancer. The dose decided on in this part of the study will become the recommended dose for the randomised Phase II trial.
Carcinoma, Squamous Cell
Radiation: Intensity Modulated Radiotherapy
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Olaparib in Addition to Cisplatin Based Concurrent Chemoradiotherapy for Patients With High Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck (HNSCC)|
- Frequency of dose limiting toxicities [ Time Frame: 6 weeks post completion of treatment ] [ Designated as safety issue: Yes ]
- Complete response rate [ Time Frame: 12 weeks post completion of treatment ] [ Designated as safety issue: No ]
- Time to loco-regional progression [ Time Frame: 2 years post completion of treatment ] [ Designated as safety issue: No ]
Experimental: single arm
All patients will receive induction chemotherapy (cisplatin and 5-FU), followed by cisplatin chemotherapy and radiotherapy in addition to oral olaparib.
Induction chemotherapy (21 day cycle)
olaparib plus chemoradiotherapy (8 weeks)
Given twice daily. Exposure will escalate by daily dose and duration.
Other Name: AZ2281Drug: cisplatin
Dose will be 35mg/m2 i.v. once weekly.Radiation: Intensity Modulated Radiotherapy
Total dose will be 70Gy in 35 fractions over 7 weeks.
This is a dose escalating Phase I/II trial evaluating the safety and tolerability of the addition of olaparib to CRT in high risk locally advanced human papillomavirus (HPV) negative Squamous Cell Carcinoma of the Head and Neck (HNSCC). A fixed dose of weekly cisplatin and intensity-modulated radiation therapy (IMRT) will be used, with doses of olaparib escalating for consecutive days and both dose level and duration will be increased through each cohort.
This Phase I trial will assess how olaparib, a poly ADP ribose polymerase (PARP) inhibitor is tolerated when added to standard chemoradiotherapy treatment.
Patients will be recruited from sites in the UK only.
A placebo controlled, randomised Phase II trial will follow once the recommended dose and schedule of olaparib has been established.