NRG-HN016 (CONCISE): New NRG Oncology Pragmatic Phase 3 Trial for Cisplatin-Ineligible Locoregionally Advanced Head & Neck Cancer Launching Soon!

04/15/2026

By Loren K. Mell MD, FASTRO – NRG-HN016 Principal Investigator
Co-Director, Hanna & Mark Gleiberman Head and Neck Cancer Center
Professor and Vice Chair, Clinical & Translational Research
UC San Diego | Department of Radiation Medicine and Applied Sciences

The NRG-HN016 (CONCISE) Trial is a randomized phase III trial comparing radiation therapy (RT) plus carboplatin/paclitaxel vs. RT plus cetuximab for patients with locoregionally advanced head and neck cancer who have a contraindication to cisplatin. CONCISE is the first trial comparing the two most commonly used regimens for this population, and the first “pragmatic” trial for solid tumors to be conducted by NRG Oncology. The pragmatic design allows for streamlined eligibility assessments and data collection and aims to conduct a real-world assessment of the comparative effectiveness of these two regimens for head and neck cancer patients who are cisplatin-ineligible.

The CONCISE trial aims to enroll 454 patients, with a primary endpoint of progression-free survival (PFS). Key secondary endpoints are overall survival, toxicity, patterns of failure, and impact on diet, eating, and speech. Patients with either stage III-IVB p16-negative or stage II-III p16-positive squamous cell carcinoma of the oropharynx, larynx, hypopharynx, or oral cavity (medically inoperable), with a contraindication to cisplatin but otherwise good overall health and performance status (i.e., fit for curative-intent treatment) are eligible. The study is powered to detect an increase in PFS of approximately 11% in the p16-negative and 7% in the p16+ subgroups for carboplatin/paclitaxel as compared to cetuximab, respectively, and is expected to take about 5 years to complete accrual.

In addition to cetuximab and carboplatin/paclitaxel, several alternatives, including carboplatin, docetaxel, and immune checkpoint inhibitors, have been studied as substitutes for cisplatin, yet no regimen has been established as standard. The CONCISE trial thus aims to establish the standard of care for this population by comparing two leading alternative strategies (i.e., doublet cytotoxic chemotherapy vs. targeted therapy) using systematic dosing schedules. The results will also define the comparator arm for future studies that seek to test promising experimental strategies in this unique and growing population.