Feasibility Trial of Pembrolizumab Plus Ultrasound-Induced Microbubble Cavitation in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
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.
• Individuals must meet all of the following inclusion criteria in order to be eligible to participate in the study:
‣ Pathologically confirmed, HPV-negative, R/M HNSCC per American Joint Committee on Cancer (AJCC) 8th Edition Staging Criteria, with CPS score \> 1
⁃ The target lesion is ultrasound-accessible, biopsy-accessible, and measurable in at least one dimension, based on RECISTv1.1 criteria.
⁃ Male or female, aged ≥18 years of age
⁃ ECOG Performance status 0-2.
⁃ Must have a life expectancy of at least 6 months as judged by the treating physician.
⁃ Adequate organ function:
• Absolute neutrophil count 1500/μl or more;
∙ Platelets 100,000/μl or more,
∙ Hemoglobin 8 g/dl or more;
∙ Bilirubin less than or equal to 1.5 x the upper limit of normal (except subjects with Gilbert syndrome, who can have total bilirubin \<3 mg/dl);
∙ AST and ALT less than or equal to 2.5x the upper limit of normal
⁃ Women of reproductive potential should have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG), which must also be confirmed as negative within 28 days of the start of study drugs.
⁃ Women of reproductive potential must use highly effective contraception methods to avoid pregnancy for 90 days after the last dose of study drugs. Women of reproductive potential is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, tubal ligation, or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL.
⁃ Men of reproductive potential who are sexually active with women of reproductive potential must use any contraceptive method with a failure rate of less than 1% per year. Men who are receiving the study medications will be instructed to adhere to contraception for 90 days after the last dose of study drugs. Men who are azoospermic do not require contraception.
‣ Informed Consent: All subjects must be able to comprehend and sign a written informed consent document.