NCT03715946

Adjuvant De-Escalated Radiation + Adjuvant Nivolumab for Intermediate-High Risk P16+ Oropharynx Cancer

Phase II Trial of Adjuvant De-Escalated Radiation + Concurrent and Adjuvant Nivolumab for Intermediate-High Risk P16+ Oropharynx Cancer

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: Robert L. Ferris, MD, PhD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This clinical trial will evaluate a new combination of treatments for Oropharyngeal Squamous Cell cancers (OPSCC), and compare it to the current standard of care (concurrent, platinum-based chemoradiotherapy). Chemoradiotherapy is efficacious, but also associated with significant toxicities and is only suitable for patients with good performance status and without severe comorbidities. The purpose of this trial is to demonstrate equivalent oncologic outcome with fewer adverse effects and improved quality of life when compared to the standard of care.

Detailed description

This study aims to enroll 135 patients (male and female, age 18+) who are newly diagnosed with resectable, squamous cell carcinoma or undifferentiated carcinoma of the oropharynx. Survival rate and treatment response of OPSCC varies based on HPV infection status and genotype; therefore, in this study, only patients who are HPV seropositive and have HPV type 16 will be enrolled. All patients will receive the same treatment, i.e. there is no active control group. In this trial, patients will undergo transoral surgery followed by de-intensified adjuvant radiotherapy plus nivolumab. The radiotherapy will consist of 45 or 50 Gy (depending on tumor volume) in 25 daily fractions, 6 fractions per week. Nivolumab will be administered at a fixed dose of 240 mg over 30 minutes IV every 2 weeks during radiotherapy, and at 480 mg over 60 minutes IV every 4 weeks for 6 doses after radiotherapy. The first dose will be given prior to the first fraction of radiation (Day 1) on Day -3 (+/- 2 days), and continued every 2 weeks (+/- 2 days). Nivolumab will thus be given in weeks 2 and 4 of radiotherapy. Adjuvant nivolumab will then be given for a total of 6 additional doses after the completion of radiotherapy every 4 weeks (+/- 7 days), starting in the second or third week after the completion of radiotherapy. Doses of nivolumab may be interrupted, delayed, or discontinued depending on how well the subject tolerates the treatment. Relevant outcome measures include disease free survival (2 year post surgery); percutaneous gastronomy dependence (1-year postsurgery); acute and late toxicity; patient-reported Quality of Life measures, locoregional control and distant metastatic control.

Conditions

• Carcinoma, Squamous Cell of Head and Neck
• Oropharynx Squamous Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Nivolumab Injection	A fully human anti-programmed death 1 (PD-1) monoclonal antibody
RADIATION	Radiotherapy (RT)	45-50 Gy accelerated fractionation in 25 daily fractions, 6 fractions per week

Timeline

• Start date: 2018-11-16
• Primary completion: 2023-03-31
• Completion: 2024-03-31
• First posted: 2018-10-23
• Last updated: 2025-01-13
• Results posted: 2025-01-13

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study