NCT07501650

Pembrolizumab Plus Ultrasound-Induced Microbubble Cavitation in Head and Neck Cancer

Feasibility Trial of Pembrolizumab Plus Ultrasound-Induced Microbubble Cavitation in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Sponsor: Thomas Jefferson University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a feasibility trial studying anti-PD-1 therapy (Pembrolizumab) among patients with R/M HNSCC, delivered with ultrasound-induced microbubble cavitation, with the goal of optimizing delivery of Pembrolizumab and tumor response to Pembrolizumab. Patients will undergo 3 infusions of Pembrolizumab plus Definity 3 weeks apart. Following each infusion, ultrasound will be directed at the primary tumor site to induce microbubble cavitation, with the goal of tumor sonoporation. The primary endpoints will be feasibility, measured based on successful recruitment of 6 participants within 1 year of initiating recruitment, with successful completion of trial procedures among at least 80 percent of patients. Secondary endpoints will include proportion of serious adverse events, clinical/radiographic response, overall survival, and progression-free survival.

Detailed description

The proposed study is a feasibility trial of Pembrolizumab plus Definity Perflutren Lipid Microsphere (Lantheus Medical Imaging), followed by ultrasound-induced microbubble cavitation (UC), which will target patients with R/M HNSCC, for which Pembrolizumab is already indicated as standard of care treatment. Patients will undergo up to 3 cycles of therapy. Participants may continue study treatment for up to 3 cycles, 3 weeks apart, from the time of initiating treatment, with 3-month safety follow-up. Participant characteristics and endpoints will be summarized through appropriate descriptive statistics-the mean and standard deviation (or median and interquartile range, if appropriate) for continuous variables, and frequency counts and percentages for categorical variables. Primary Analysis Among all patients enrolled, feasibility will be assessed, defined as enrollment of 6 participants within 1 year of study initiation, and completion of all trial procedures, including 3 cycles of PD treatment and follow-up visits, among at least 80 percent of enrolled patients. Recruitment feasibility (primary objective secondary endpoint) will be assessed as the number of participants enrolled during the first 12 months from site activation. Success is defined as 6 participants enrolled within this window. The investigators will summarize the 6-month enrollment count and accrual rate descriptively. Protocol completion feasibility (primary objective primary endpoint) will be assessed as the proportion of enrolled participants who complete all pre-specified trial procedures (all scheduled visits/assessments through end-of-treatment and the primary follow-up time point). The denominator is all enrolled participants. Unknown or missing completion status will be counted as not complete. Success is defined as at least 80 percent completion. The investigators will report the completion proportion with 95 percent exact binomial (Clopper-Pearson) confidence intervals. Secondary Analysis Assessment of the following secondary metrics is anticipated using descriptive statistics; no hypothesis tests are planned. Where applicable, 95% exact binomial CIs (Clopper-Pearson) will be provided for proportions. * Proportion of serious adverse events (according to CTCAEv5.0) * Objective Response Rate (Clinical/Radiographic Response) * Progression Free Survival * Overall Survival Exploratory/Correlative Analysis/Assessments Assessment of the following correlative metrics through descriptive statistics is anticipated. No hypothesis tests are planned. * IHC measures of the prevalence of intratumoral immune cell populations including but not limited to CD8, CD45, FoxP3, PD-L1 * IHC-based measures of myeloid lineage differentiation markers:CD3, CD4, CD8, CD11b, CD11c, CD14, CD33, CD163, CD204, and HLA-DR, also analyzed with flow cytometry * Luminex panel of inflammatory markers with the Milliplex MAP Human Cytokine/chemokine kit * Variant files (VCFs) including point mutations, insertions, and deletions, as well as HLA-type, identified from whole exome sequencing * Epitope analysis of neoantigens and HLA typing using RNAseq * Spatially-resolved, digital quantitation of mRNA using Nanostring GeoMx DSP * Quantitative-CEUS parameters collected during treatment infusion, correlated with treatment efficacy and TME parameters Interim Analyses and Stopping Rules The study will be discontinued if there are more than 2 "study-limiting adverse events" at any point during the trial, with a "study-limiting adverse event" being defined as any grade 3 or higher cardiac, endocrine, or immunologic adverse event, or any grade 4 or higher adverse event.

Conditions

• Head and Neck Cancer
• Head and Neck Small Cell Carcinoma
• Metastatic Head and Neck Cancer
• Recurrent Head and Neck Cancer

Interventions

Type	Name	Description
DRUG	Pembrolizumab	Pembrolizumab will be administered intravenously at a dose of 200 mg every 3 weeks for up to 3 cycles
DRUG	Definity	Definity will be administered intravenously during each treatment cycle to facilitate ultrasound-induced microbubble cavitation.
DEVICE	Ultrasound-Induced Microbubble Cavitation	Therapeutic Ultrasound will be applied to the tumor site during and following the Definity infusion to induce microbubble cavitation using modified ultrasound parameters.

Timeline

• Start date: 2026-03-18
• Primary completion: 2027-03-01
• Completion: 2028-03-01
• First posted: 2026-03-30
• Last updated: 2026-03-30

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study