A phase II study of personalized ultrafractionated stereotactic adaptive radiotherapy for palliative head and neck cancer treatment (PULS-Pal): a single-arm clinical trial protocol

Background: Many patients with head and neck cancer will not be candidates for standard of care definitive treatments though often require palliative treatments given the frequent symptoms associated with head and neck cancer. While existing palliative radiotherapy regimens can provide adequate symptom control, they have limitations particularly with respect to local control which is becoming more important as advances in systemic therapy are improving survival. Personalized ultrafractionated stereotactic adaptive radiotherapy (PULSAR) is a novel radiotherapy regimen which leverages advances in radiotherapy treatment technology and extended interfraction intervals to enable adaptive radiotherapy and possible synergy with the immune system. Additionally, HyperArc© (Varian Medical Systems, Inc.) radiotherapy planning software allows for safe dose-escalation to head and neck tumors. Methods: This single-arm phase II study will prospectively evaluate PULSAR with HyperArc software for palliative treatment of head and neck cancer. Patients with de novo or recurrent, localized or metastatic, head and neck cancer who are ineligible for or decline standard of care definitive treatments are eligible for enrollment. Forty-three patients will receive an 11 Gray fraction of radiation every two weeks for a total of five fractions and dose of 55 Gy. Adaptive radiotherapy planning is permitted. A safety and feasibility evaluation will be performed after enrollment of the first fifteen patients whereby the trial will continue if less than five patients experience a CTCAEv5.0 grade 3 or higher toxicity definitely attributable to PULSAR during or within thirty days after its completion. The primary endpoint is one-year local head and neck tumor control. Secondary endpoints include safety, disease progression-free and overall survival, symptomatic impact, frequency of re-simulation and/or adaptive planning, and radiation dosimetry of PULSAR. Additionally, enrolled patients are permitted to receive immunotherapy during PULSAR, which may allow for the analysis of the safety and efficacy of this combination. Discussion: The PULS-Pal trial is the first prospective study of PULSAR with HyperArc software for head and neck cancer. We hypothesize that this radiotherapy regimen will lead to improved local tumor control compared with historical controls in patients undergoing palliative radiotherapy for head and neck cancer. Trial Registration: Clinicaltrials.gov identifier: NCT06572423. Date of registration: August 28 ^th , 2024. https://clinicaltrials.gov/study/NCT06572423.