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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
3
Pembrolizumab
Radiotherapy - Standard Treatment
Chemotherapy - Standard Treatment
Royal Marsden Hospital NHS Foundation Trust
London, United Kingdom
Number and Percentage of Patients With Dose Limiting Toxicities (DLT).
To establish the maximum tolerated dose that can safely be combined with platin-based chemoradiotherapy in patients with HPV-ve and HPV+ve LA-SCCHN.
Time frame: Six weeks after the completion of chemoradiotherapy
Acute Toxicity as Measured During Treatment by CTCAE v4.0
Count and percentage of patients with any CTCAE graded toxicity from start of trial treatment until 6 weeks following end of treatment
Time frame: Up until 6 weeks after the end of chemoradiotherapy (week 14 of the study)
Percentage of Progression Free Survival at 6, 12 and 24 Months Post Treatment Start.
Calculated as percentage of evaluable patients alive and disease free at each time point.
Time frame: Six months, one year and two years
Percentage of Overall Survival at 6, 12 and 24 Months
Calculated as percentage of evaluable patients alive at each time point
Time frame: Six months, one year and two years
Percentage of Patients With Clinical Benefit (CR/PR/SD) Using RECIST at 6, 12 and 24 Months
Calculated as percentage of evaluable patients with clinical benefit (CR/PR/SD) using RECIST at 6, 12 and 24 months
Time frame: Six months, one year and two years
Percentage of Patients With Any Grade 1 Plus RTOG Toxicities
Calculated as percentage of patients with any grade 1 toxicities from start of treatment up to 52 weeks from the end of radiotherapy.
Time frame: 52 weeks from the end of radiation therapy (week 7)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.