NCT02819752

PEmbrolizumab Combined With Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck

Phase I Dose-escalation Study of PEmbrolizumab (MK3475) Anti-PD1 Immune Checkpoint Inhibitor Combined With Radical Chemoradiotherapy in Patients With Stage IV Squamous Cell Carcinoma of the Head and Neck

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: Royal Marsden NHS Foundation Trust · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study aims to establish whether the combination of pembrolizumab (MK-3475) and conventional cisplatin-based chemoradiotherapy is tolerable and results in acceptable levels of acute and late toxicity in patients with stage IV LA-SCCHN. In particular, the study will provide data on the levels of mucosal and cutaneous toxicity within the radiation fields, as these are the primary acute toxicities associated with this treatment regimen. In addition, toxicity outside the radiation portals (which may theoretically be exacerbated by radiation) will be studied. However, all toxicity will be monitored. This study will also give an indication of the activity of pembrolizumab in LA-SCCHN because we are deliberately selecting a group of patients with high- and intermediate-risk disease who have a significant chance of experiencing loco-regional or systemic failure.

Detailed description

This will be a single centre phase 1 dose-escalation study to confirm the safety of combining pembrolizumab with standard platin-based chemoradiotherapy in patients with stage IV high- and intermediate-risk locally-advanced squamous cell carcinoma of the head and neck (LA-SCCHN). 6-36 patients (18 HPV+ve and 18 HPV-ve) will be recruited in a standard 3+3 dose-escalation trial design with an expansion cohort at the maximum tolerated dose (or 200 mg, if no DLT is defined). A pre-loading dose of 100 or 200mg (dependent on dosing level) of pembrolizumab will be given once the patient has completed the screening period. Patients will then return 2 weeks later to begin cycle 1 of a regimen of pembrolizumab 3 weekly at a dose of 100 or 200mg (dependent on dosing level) for a total of 7 cycles (3 during chemoradiotherapy and 4 after chemoradiotherapy). Parallel studies in HPV-ve and HPV +ve disease will be conducted (note these patients may have different patterns of co-morbidity and, hence, different treatment-related toxicities). The primary endpoint of the study will be safety and tolerability. Dose-limiting acute toxicity will be assessed during administration of study drug according to CTCAEv4.0. The maximum tolerated dose of study drug (or 200 mg in the absence of DLT) will be used in a subsequent randomised phase 2 study comparing standard-of-care therapy with standard-of-care therapy plus study drug.

Conditions

• Squamous Cell Carcinoma of the Head and Neck
• Squamous Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Pembrolizumab	Pembrolizumab
RADIATION	Radiotherapy	Radiotherapy - Standard Treatment
DRUG	Chemotherapy	Chemotherapy - Standard Treatment

Timeline

• Start date: 2017-07-12
• Primary completion: 2019-11-28
• Completion: 2019-11-28
• First posted: 2016-06-30
• Last updated: 2026-04-09
• Results posted: 2025-12-18

Locations

1 site across 1 country: United Kingdom