NCT04938609

Neoadjuvant Immunoradiotherapy in Head & Neck Cancer (NIRT 2-HNC)

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: Providence Health & Services · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the efficacy of neoadjuvant immunoradiotherapy (NIRT) prior to surgery for the treatment of stage III and IVA HPV- HNSCC.

Detailed description

This clinical trial uses pembrolizumab and radiotherapy prior to definitive surgical resection of tumors in patients with Head and Neck Squamous Cell Carcinoma (OHNSCC) with the primary objective of determining the safety and efficacy of preoperative immunoradiotherapy. In addition, tumor tissue, microbiome samples, and peripheral blood will be obtained for exploratory immunologic end points including measurements of tumor infiltrating immune cell populations based on flow cytometry and immunohistochemistry as well as circulating immunological parameters. Estimated duration of 52 weeks: neoadjuvant immunoradiotherapy +/- surgery at week 7, followed by risk adapted adjuvant therapy, per standard of care. Patients will then be treated with adjuvant pembrolizumab every 3 weeks for 14 additional doses (17 doses total). Phase II efficacy study (n = 28, total) to assess rate of down-staging after neoadjuvant immunoradiotherapy using Simon's two-stage design (futility assessment at n = 12). Phase I studied nivolumab in 10 patients with HPV+ HNSCC, the results of which suggest that the combination is safe and efficacious. The phase II portion of study will evaluate the efficacy of neoadjuvant pembrolizumab in combination with SBRT as a safe means to down-stage HNSCC prior to surgical resection, improve quality of life, and enhance local control and overall survival. Patients will be followed for disease free and overall survival at 5 years. Eligible patients may be enrolled unless a rate of unplanned surgical delay attributed to immunoradiotherapy is found to exceed 33% after enrollment of the first 10 patients. We estimate at least 2 patients per month will be enrolled. Time to full accrual is estimated as 2.5 years.

Conditions

• Head and Neck Cancer
• Head and Neck Squamous Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Pembrolizumab	Pembrolizumab is a humanized anti-PD-1 mAb of the IgG4/kappa isotype with a stabilizing S228P sequence alteration in the Fc region.
RADIATION	Stereotactic Body Radiation Therapy (5 days)	8Gy x 3 (Mon-Fri) GTV+3mm
PROCEDURE	Surgical Resection	Surgical Resection of Tumor

Timeline

• Start date: 2022-01-11
• Primary completion: 2027-01-11
• Completion: 2031-01-11
• First posted: 2021-06-24
• Last updated: 2026-04-09

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study