NCT02308072

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

A Phase I Trial of Olaparib in Addition to Cisplatin-based Concurrent Chemoradiotherapy for Patients With High Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck (NHSCC)

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 70 (estimated)
• Sponsor: University College, London · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The phase I trial aims to determine the recommended phase II dose (RP2D) and schedule of olaparib in combination with standard cisplatin-based chemoradiotherapy, in patients with high-risk locally advanced squamous cell carcinoma of the head and neck (HNSCC), by assessing the safety and tolerability of the treatment combination.

Detailed description

ORCA-2 is a phase I trial in patients with locally advanced, with or without metastatic nodal disease. Patients will receive olaparib (a PARP inhibitor) in combination with standard cisplatin-based chemotherapy and intensity modulated radiotherapy (IMRT). Olaparib, cisplatin and radiotherapy will be given in combination every week for a maximum of 7 weeks. Prior to starting combination treatment, olaparib will be started 7 days before the first week of combination treatment. Olaparib will be given twice daily on days 1-3 of each week of treatment (either alone during week 0 or in combination with chemotherapy and radiotherapy during weeks 1-7). Cisplatin will be started on day 1 of each week, and given once a week during radiotherapy treatment for a total of 7 weeks. Radiotherapy will be delivered on days 1-5 of each week using IMRT, for a total of 7 weeks. The phase I trial aims to determine the recommended phase II dose of olaparib (50mg, 100mg, 150mg or 200mg bd) - the dose of olaparib patients receive will depend on the dose under investigation at the time of patient registration. Dose escalation will be guided by the two-dimensional dose escalation design called Product of Independent Beta Probabilities escalation (PIPE). It will recommend the choice of dose/duration combination cohort of olaparib for subsequent patients by estimating the contour that divides dose/duration combination cohorts to be those above the target toxicity rate (equal to 33%) and those below. The recommended phase II cohort(s) are those that have been experimented on during the trial and are also closest to (but not above) the estimated contour calculated using all trial data.

Conditions

• Head and Neck Cancer

Interventions

Type	Name	Description
DRUG	Olaparib	50 mg, 100 mg, 150 mg or 200 mg taken twice daily (depending on dose under investigation at time of registration) on days 1-3, 1-4 or 1-5 (depending on allocation of treatment schedule) of each week of treatment.
DRUG	Cisplatin	35 mg/m\^2 IV on day 1 of each week of treatment during radiotherapy for a total of 7 weeks (total overall dose 245 mg/m\^2)
RADIATION	IMRT	2 Gy delivered in 35 fractions, on days 1-3, 1-4 or 1-5 each week for up to 7 weeks (total overall dose delivered 70 Gy)

Timeline

• Start date: 2015-09-01
• Primary completion: 2020-06-01
• Completion: 2025-02-01
• First posted: 2014-12-04
• Last updated: 2024-05-08

Locations

3 sites across 1 country: United Kingdom